RESUMO
The objective of the investigation was to assess whether circulating adhesion molecules, von Willebrand factor (vWf) and endothelin-1 are elevated in patients with mild uncomplicated essential hypertension without further risk factors of atherosclerosis and whether they could serve as indicators of endothelial dysfunction in this form of hypertension. Furthermore the authors investigated the effect of ACE inhibitor treatment (ACEI), quinapril, on the level of these markers of endothelial dysfunction. The level of adhesion molecules [intercellular cytoadhesion molecule-1 (ICAM-1), E-selectin, P-selectin], von Willebrand s factor (vWf) and endothelin-1 were assessed in patients with mild essential hypertension without further cardiovascular risk factors or clinical manifestations of atherosclerosis before and after quinapril treatment (n = 25) and compared with normotensive controls (n = 29). The results of the examinations provided evidence that contrary to controls the hypertensive subjects had significantly higher ICAM-1 levels (237.8 vs. 207.8 ng/ml, P = 0.02) vWf (118 vs. 106 IU/dl, p < 0.05) and endothelin-1 (5.81 vs. 5.15 fmol/ml, p < 0.05). Three-month treatment of hypertensive patients with ACEI led to a significant drop of endothelin-1 levels (5.81 vs. 5.26 fmol/ml, p = 0.01). The authors proved also an unequivocal declining trend of other cytoadhesion molecules and vWf after ACEI treatment, the changes however were not statistically significant. From the investigation it may be concluded that also patients with uncomplicated essential hypertension without other cardiovascular risk factors or clinical manifestations of atherosclerosis have significantly elevated plasma levels of ICAM-1, vWf and endothelin-1. Higher concentrations of these factors suggest endothelial dysfunction already in mild forms of essential hypertension without further risk factors or cardiovascular complications. A significant drop of endothelin-1 and declining trend of the other investigated indicators suggest that ACEI treatment can favourably influence endothelial dysfunction in hypertensive patients also independently on reduction of the BP.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Moléculas de Adesão Celular/sangue , Endotelinas/sangue , Endotélio Vascular/fisiopatologia , Hipertensão/sangue , Isoquinolinas/uso terapêutico , Tetra-Hidroisoquinolinas , Fator de von Willebrand/análise , Anti-Hipertensivos/uso terapêutico , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , QuinaprilRESUMO
OBJECTIVE: Since beta2-adrenergic receptors (beta2AR) can influence blood pressure not only by vasodilation, but also participate in noradrenaline release from sympathetic nerve endings, we have studied whether Arg16Gly polymorphism of the beta2AR gene is associated with predisposition to essential hypertension and increased plasma noradrenaline concentration in offspring from normotensive (SN) and hypertensive parents (SH). DESIGN AND METHODS: The study population consisted of 105 young SN and 101 SH subjects matched for age and body mass index. Arg16Gly polymorphism of the beta2AR gene was determined by polymerase chain reaction (PCR) technique and subsequent incubation with NcoI restriction enzyme. Resulting fragments were separated using electrophoresis on a 4.2% Metaphor agarose gel. RESULTS: SH already had significantly higher systolic BP, and a tendency to higher diastolic BP than the SN group. The frequency of Arg/Arg homozygotes was significantly increased in SH when compared to SN (25% vs 15%). Results of logistic regression analysis showed the highest relative risk for the Arg/Arg genotype and suggested a recessive action of the Arg16 variant. There was an increased diastolic BP in Arg/Arg homozygotes of the SN group (p = 0.029). This genotype also had a tendency to increased heart rate in both groups (p = 0.049). There was no relationship of this polymorphism with plasma noradrenaline concentration. CONCLUSION: Our findings suggest that genetic variability of the beta2AR gene is implicated in predisposition to essential hypertension. However, the contradictory results between individual studies indicate that the action of the beta2AR gene is indirect, through multiple intermediate phenotypes and gene interactions.
Assuntos
Hipertensão/genética , Polimorfismo Genético , Receptores Adrenérgicos beta 2/genética , Adulto , Estudos de Casos e Controles , Análise Mutacional de DNA , Saúde da Família , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Modelos Logísticos , Masculino , Mutação de Sentido Incorreto , Razão de ChancesRESUMO
The aim of the study was to examine whether the circulating cell adhesion molecules, von Willebrand factor (vWf) and endothelin-1, are elevated in patients with essential hypertension with no other risk factors for atherosclerosis and thus may serve as a markers of endothelial dysfunction in uncomplicated hypertension. Furthermore, the effect of treatment with the ACE inhibitor, quinapril, on levels of endothelial dysfunction markers were studied. The levels of adhesion molecules (intercellular cell adhesion molecule-1 [ICAM-1], E-selectin, P-selectin), von Willebrand factor (vWf) and endothelin-1 were measured in patients with hypertension without any other risk factors of atherosclerosis before and after treatment with quinapril (n = 22) and in normotensive controls (n = 22). Compared with normotensive subjects, the hypertensive patients had significantly higher levels of ICAM-1 (238 vs 208 ng/ml, P = 0.02), vWf (119 vs 105 IU/dl, P < 0.05) and endothelin-1 (5.76 vs 5.14 fmol/ml, P < 0.05). Three-month treatment of hypertensive patients with quinapril led to a significant decrease in the levels of endothelin-1 (5.76 vs 5.28 fmol/ml, P < 0.01). We did not observe significant changes in the levels of adhesion molecules and vWf after ACE inhibitor treatment, although a trend toward a decrease was apparent with all these parameters. Patients with uncomplicated hypertension with no other risk factors of atherosclerosis had significantly elevated levels of ICAM-1, vWf, and endothelin-1. Our data suggest that these factors may serve as markers of endothelial damage even in uncomplicated hypertension. In hypertensive patients, treatment with the ACE inhibitor quinapril resulted in a significant decrease in endothelin-1 levels. These findings indicate a beneficial effect of ACE inhibitors on endothelial dysfunction in hypertensive patients.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Endotelina-1/sangue , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Molécula 1 de Adesão Intercelular/sangue , Isoquinolinas/uso terapêutico , Tetra-Hidroisoquinolinas , Doenças Vasculares/sangue , Doenças Vasculares/tratamento farmacológico , Fator de von Willebrand/análise , Adulto , Idoso , Endotelina-1/efeitos dos fármacos , Humanos , Hipertensão/fisiopatologia , Molécula 1 de Adesão Intercelular/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Quinapril , Doenças Vasculares/fisiopatologia , Fator de von Willebrand/efeitos dos fármacosRESUMO
OBJECTIVES: To study candidates for liver transplant before and 6 weeks after transplant, and to elucidate the role of endothelial dysfunction and plasma endothelin concentrations in the development of hypertension. DESIGN PROSPECTIVE: follow-up study. SETTING: Institutional, outpatient. PATIENTS: and controls Fifteen patients (11 men, four women, mean age 46.7+/-13.2 years) with end-stage liver disease (ESLD) and healthy volunteers of comparable age and sex. METHODS: We performed office blood pressure readings and 24 h ambulatory blood pressure monitoring (ABPM), measurements of endothelial-dependent vasodilatation using high-resolution ultrasound in the brachial artery at rest and during reactive hyperemia, and plasma endothelin-1 assays 3 months before and 6 weeks after the transplant. RESULTS: Office systolic and diastolic blood pressures increased significantly 6 weeks after liver transplantation (from 116.6+/-14.1 to 139.9+/-19.5 mmHg and from 68.6+/-9.5 to 84.1+/-9.8 mmHg, respectively; both P < 0.001). Hypertension based on office blood pressure readings increased from 6.7 to 40% (P < 0.05). Mean 24 h systolic blood pressure increased from 118.7+/-10.3 to 140.0+/-19.0 mmHg (P < 0.001), mean 24 h diastolic blood pressure increased from 86.0+/-7.7 to 104.8+/-13.9 mmHg (P < 0.001) and heart rate increased from 74.8+/-10.2 to 80.2+/-8.2 beats/min (P < 0.05). Brachial artery flow-mediated dilatation did not change throughout the study (before transplant: 4.2+/-4.0%; after transplant: 6.3+/-5.4%; NS) and did not differ from that in controls (5.2+/-3.8%). Plasma endothelin-1 was increased in patients with ESLD (15.3+/-2.6 pg/ml) compared with controls (5.6+/-0.4 pg/ ml; P < 0.001) and remained unchanged 6 weeks after liver transplantation (14.1+/-3.7 pg/ml). CONCLUSION: Our results show increased blood pressure with suppressed circadian blood pressure variability in liver graft recipients 6 weeks after transplant and no change in endothelial function and plasma endothelin concentrations. Therefore, the blood pressure increase documented in our study cannot be explained by endothelial dysfunction. Twenty-four hour ABPM should be performed routinely in patients who have undergone liver transplant.
Assuntos
Pressão Sanguínea , Endotelina-1/sangue , Endotélio Vascular/fisiopatologia , Falência Hepática/fisiopatologia , Falência Hepática/cirurgia , Transplante de Fígado , Adulto , Determinação da Pressão Arterial/métodos , Monitorização Ambulatorial da Pressão Arterial , Artéria Braquial/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Visita a Consultório Médico , Concentração Osmolar , Período Pós-Operatório , Estudos Prospectivos , Valores de Referência , Vasodilatação/fisiologiaRESUMO
Endothelial nitric oxide synthase (eNOS) produces nitric oxide (NO) which, after diffusing into vascular smooth muscle cells, activates guanylate cyclase leading to vasodilatation. A polymorphism (894G to T) in exon 7 of the eNOS gene causes the conversion of Glu to Asp in position 298. The recently described crystal structure of the heme domain of eNOS protein shows that Glu298 is fully solvent accessible and distant from regions integral to enzyme function. Searching for phenotypic expression of eNOS gene variants, we genotyped a group of patients with essential hypertension (H, n = 119) for the Glu298Asp polymorphism and compared them with age- and sex-matched healthy normals (N, n = 85). To specify phenotypic expression further, the hypertensive patients were subdivided into one group that responded well to regular antihypertensive therapy (CH, n = 45) and one group that was resistant to the therapy (RH, n = 74). Patients with BP higher than 140/90 mmHg when on adequate lifestyle modification and triple-combination therapy (including diuretics) were considered resistant. In RH and H groups, a significantly higher frequency of T alleles (P = 0.022 and P = 0.046, respectively) was found compared to normotonics (N). In well-controlled hypertonics, the same tendency was found, but did not reach statistical significance. The Glu298Asp polymorphism may contribute to the complex pathogenesis of essential hypertension and may be a factor in the resistance of these patients to conventional antihypertensive therapy. The presence of this allele may thus be predictive of the patients' therapeutic response.
Assuntos
Substituição de Aminoácidos , Hipertensão/genética , Óxido Nítrico Sintase/genética , Polimorfismo Genético , Antagonistas Adrenérgicos beta/uso terapêutico , Alelos , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/genética , Bloqueadores dos Canais de Cálcio/uso terapêutico , Diuréticos/uso terapêutico , Resistência a Medicamentos/genética , Quimioterapia Combinada , Frequência do Gene , Testes Genéticos , Genótipo , Humanos , Hipertensão/tratamento farmacológico , Estilo de Vida , Pessoa de Meia-Idade , Modelos Moleculares , Óxido Nítrico Sintase Tipo III , Fenótipo , Valor Preditivo dos TestesRESUMO
Left ventricular (LV) hypertrophy is a strong predictive factor for cardiovascular morbidity and mortality. LV structure and function are influenced by many variables, including genetic background. The potential role of gene polymorphisms of different components of the renin angiotensin system remains controversial. The aim of this study was to determine the influence of deletion/insertion (D/I) polymorphism of the angiotensin-converting enzyme (ACE) gene and M235-->T polymorphism of the angiotensinogen (AG) gene on left ventricular morphology and function in young normotensive men. The study included 110 normotensive healthy males (mean age 24 +/- 4 years, age range 18 to 34 years) who were assessed by echocardiography for LV structure and function. In all subjects ACE D/I polymorphism was evaluated using a polymerase chain reaction (PCR) method. M235-->T polymorphism assessment was available in 98 individuals. Significant differences between groups according to ACE I/D or AG M235-->T polymorphisms were not found for parameters of LV morphology or for parameters of systolic and diastolic function. When subjects with DD or ID genotypes were grouped, their LV mass index was higher than that in subjects with II genotypes (86 +/- 14 vs 79 +/- 15, r = 0.033, p = 0.05). There were no significant differences among other variables. In a population of young normotensive men where the influence of confounding variables such as age, gender and associated pathological conditions is minimized, the gene polymorphisms of ACE I/D and AG M235-->T are not important determinants of LV structure and function.
Assuntos
Angiotensinogênio/genética , Ecocardiografia , Peptidil Dipeptidase A/genética , Polimorfismo Genético/fisiologia , Adulto , Elementos de DNA Transponíveis/fisiologia , Deleção de Genes , Genótipo , Ventrículos do Coração , Humanos , Masculino , Polimorfismo Genético/genética , Valores de ReferênciaRESUMO
OBJECTIVE: We have studied possible association between predisposition to essential hypertension, plasma noradrenaline level and two polymorphisms of the gene for tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine biosynthesis. DESIGN AND METHODS: One hundred and one normotensive sons from normotensive parents (SN) and 107 normotensive sons of hypertensive families (SH) were studied. Tetranucleotide TCAT repeat and Va181Met polymorphisms of the TH gene were determined by polymerase chain reaction (PCR) technique. RESULTS: SH had higher systolic BP and plasma noradrenaline concentration than the SN group. No significant difference was found between the allele and genotype frequencies in the SH and SN groups for both polymorphisms. The two polymorphisms were in tight linkage disequilibrium. The CD genotype of the microsatellite marker was associated with increased plasma noradrenaline concentration in both groups. Genotypes AB, AE and BB of the TCAT repeat polymorphism and genotypes VM and MM of the Va181Met polymorphism exhibited the greatest difference in plasma noradrenaline concentration between the SH and SN groups. CONCLUSION: The studied TH polymorphisms do not appear to be associated with family history of essential hypertension. Nevertheless, some genotypes of TH might be related to disturbance of plasma noradrenaline concentration.
Assuntos
Substituição de Aminoácidos , Hipertensão/genética , Repetições de Microssatélites , Mutação de Sentido Incorreto , Polimorfismo Genético , Tirosina 3-Mono-Oxigenase/genética , Adulto , Análise Mutacional de DNA , Dopamina/sangue , Epinefrina/sangue , Predisposição Genética para Doença , Genótipo , Humanos , Hipertensão/sangue , Desequilíbrio de Ligação , Masculino , Norepinefrina/sangueRESUMO
An elevated plasma level of endothelin-1 was reported in several cardiovascular conditions including unstable angina pectoris and myocardial infarction. The present study was designed to evaluate the time course of the endothelin-1 release in unstable angina pectoris and to assess its relationship to the development of myocardial infarction and coronary vessel occlusion. The cohort studied included 32 patients with the clinical diagnosis of unstable angina pectoris who had been admitted to the coronary care unit and subsequently underwent coronary angiography (group A). Fourteen patients with chronic stable angina pectoris referred to routine diagnostic coronary angiography served as the control group (group B). A significant difference in the endothelin-1 plasma level was found between both groups, the values being 10.2 +/- 5.3 and 6.0 +/- 3.1 pg/ml (p < 0.01), respectively. There were, however, no significant differences between the following subdivisions of group A: patients with and without subsequent myocardial infarction; those with angiographically documented occlusion of at least one major branch of the coronary artery and no occlusion; and finally, those with persisting symptoms of angina pectoris and with favorable response to treatment. Neither was there any difference found among the subgroups differing in the time interval between the onset of chest pain and blood sampling. The time course of endothelin plasma concentrations showed elevated values lasting for more than 96 h after the index episode of prolonged chest pain. No correlation with the subsequent clinical course could be inferred. Thus, plasma endothelin level was elevated in patients with unstable angina pectoris and myocardial infarction and the increase persisted for several days after the onset of symptoms.
Assuntos
Angina Instável/sangue , Endotelina-1/sangue , Infarto do Miocárdio/sangue , Adulto , Idoso , Angina Instável/diagnóstico por imagem , Biomarcadores/sangue , Angiografia Coronária , Endotelina-1/biossíntese , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Prognóstico , Valores de Referência , Sensibilidade e Especificidade , Fatores de TempoRESUMO
The main task in hypertension research is to explain genetic causes of a raised blood pressure. It is anticipated that advances in this area will promote not only a better understanding of the pathophysiology of hypertension but will make a more aimed approach to early diagnosis, prevention and therapy of essential hypertension possible. The greatest problems in investigations of the heredity of hypertension are; a) in cardiovascular control mechanisms several genes participate; b) factors of the external environment which act on a long-term basis interfere with the relationship of the genotype and phenotype individually, within the family and regionally; c) the blood pressure is a continuous variable and the definition of the phenotype of hypertension is inaccurate; d) inadequate number of family members where hypertension segregates. New methods in molecular biology and statistical genetics made it possible to assess a number of highly polymorphous genetic signs in several candidate genes and the subsequent investigation of their possible role in the pathogenesis of hypertension. The majority of hitherto accomplished studies was concentrated on genes coding different components of the renin-angiotensin system: renin, ACE, angiotensinogen and angiotensin II receptors. So far the most promising, though not consistent, results were obtained for angiotensinogen and the insulin receptor. Work focused on the relationship of the polymorphism of genes for ANF, growth hormone and kallikrein to essential hypertension is negative. The genetic heterogeneity of the human population, physiological differences in the genesis of high blood pressure in different ethnical groups and inaccurate measurements of specific phenotypes can contribute to different results of different studies.
Assuntos
Hipertensão/genética , Genes , Humanos , Biologia MolecularRESUMO
Endothelin plays an important role in cardiovascular pathology. As one of the most important endothelium-derived vasoconstrictor substances, endothelin together with endothelium-derived vasodilating factor control vascular tone and contribute to the vasoconstrictory response if the production of endothelium-derived vasodilating factor is impaired. The aim of the study was to assess the changes of the local endothelin level in coronary circulation immediately after percutaneous transluminal coronary angioplasty (PTCA). Plasma endothelin levels were measured in blood samples from the peripheral vein and ostium of the coronary artery before the angioplasty, and from the distal coronary artery just beyond the dilated segment and the peripheral vein immediately after the procedure. The plasma endothelin level was significantly higher in the ostium of the coronary artery already prior to PTCA as compared to the peripheral vein (10.9 +/- 3.4 vs. 7.2 +/- 2.1 pg/ml, p < 0.005). There was no change in the endothelin level in the coronary artery distal to the dilated segment immediately after the procedure as compared to the initial level, although this level was higher than the postangioplasty venous level (9.8 +/- 2.9 vs. 7.7 +/- 2.0 pg/ml, p < 0.005). Individual changes in coronary-artery plasma endothelin levels as a response to coronary angioplasty were disparate. An increase and a decrease in coronary artery plasma endothelin levels by more than 2 pg/ml after coronary angioplasty were observed in 3 and 6 subjects, respectively. In conclusion, increased plasma endothelin levels were found in blood samples drawn from the coronary artery as compared to the peripheral vein. There was no further change in the plasma endothelin level in the coronary artery distal to the dilated segment after angioplasty; however, the individual responses were disparate.
Assuntos
Angina Pectoris/sangue , Angina Pectoris/terapia , Angioplastia Coronária com Balão , Circulação Coronária/fisiologia , Vasos Coronários , Endotelinas/sangue , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioimunoensaio , Vasoconstrição/fisiologia , VeiasRESUMO
Our paper is discussing the presence and intensity of metabolic, humoral and haemodynamic abnormalities in mild middle-aged essential hypertensives (EH) and in hereditary predisposed still normotensive offspring from hypertensive families and their possible association with candidate genes changes. Four groups of subjects were compared (middle-aged normotensive controls (n = 21), corresponding patients with EH (n = 21), normotensive offspring from hypertensive (SH) (n = 56) and normotensive families (SN) (n = 56). Our results demonstrate that middle-aged patients with EH in our country have the same indices of hyperinsulinemia, impared glucose tolerance and insulin-sensitivity as previously described for other populations. They are accompanied by higher plasma concentrations of vasopressor substance like catecholamines, endothelin and lower levels of vasodepressor substances as ANP and kallikrein. The finding of similar, but quantitatively less expressed metabolic and humoral changes in SH but not in SN support the evidence for hereditary background of these abnormalities. The humoral and metabolic abnormalities may participate in BP elevation and in morphological and functional changes of left ventricle seen in SH (higher LV mass index, impaired diastolic filling). We did not prove an association between BP and polymorphism of ACE and angiotensinogen genes, however, our findings of association of DD genotype for ACE and M235 for angiotensinogen with higher insulinemia, plasma catecholamines and plasma renin activity evoke the hypothesis, whether the bearers of these genotypes, exposed for long-time to the higher concentrations of vascoactive substances, are not the subset of hereditary threatened subjects in whom clinically evident EH will manifest during their life.
Assuntos
Hipertensão/fisiopatologia , Adulto , Angiotensinogênio/genética , Peptídeo C/sangue , Suscetibilidade a Doenças , Ecocardiografia , Epinefrina/sangue , Epinefrina/genética , Genótipo , Humanos , Hiperinsulinismo/complicações , Hipertensão/diagnóstico por imagem , Calicreínas/urina , Masculino , Norepinefrina/sangue , Norepinefrina/genética , Peptidil Dipeptidase A/genética , Polimorfismo GenéticoRESUMO
Arterial hypertension is not only a haemodynamic abnormality, but it is associated with several metabolic and humoral changes. Heredity appears to be participating in the pathogenesis of essential hypertension (EH). We studied whether some metabolic, humoral and haemodynamic changes could be detected in genetically predisposed normotensive sons of hypertensive families (SH) compared with normotensive sons of normotensive parents (SN). The study groups consisted of 40 young SN and 40 SH matched for age and body mass index (BMI). Blood samples for laboratory determination were taken under basal conditions and 90 min after a 75 g glucose load. SH already had a higher systolic blood pressure (BP) (120.7 +/- 1.7 mm Hg) and a tendency to a higher diastolic BP than the SN group. In spite of the fact that both basal and stimulated glycemia did not differ significantly between the study groups, significantly higher glucose-stimulated immuno-reactive-insulin (IRI) was found in SH (80.1 +/- 7.06 vs 62.9 +/- 5.76 uU/l). Higher plasma concentration of catecholamines in SH indicate their higher sympathetico-adrenal activity. The groups did not differ significantly in basal and stimulated plasma renin activity (PRA), aldosterone and atrial natriuretic peptide (ANP). There was a tendency for higher levels of endothelin (ET) in the plasma of SH. The glucose load increased as expected, glycemia, IRI and C-peptide, but ANP and ET concentrations were unexpectedly reduced. These abnormalities were associated, in SH, with higher left ventricle (LV) mass index and impaired diastolic filling. Persistence of high LV mass index, even after adjustment for respective systolic BP, suggests the participation of more than haemodynamic stress in the increase of LV mass. Our results suggest that in normotensive genetically predisposed subjects from hypertensive families, some metabolic and humoral abnormalities can already be detected. They might be responsible for the higher BP readings with subsequent manifestations of hypertension and LV morphological and functional abnormalities.
Assuntos
Pressão Sanguínea , Hemodinâmica , Hormônios/sangue , Hipertensão/genética , Hipertensão/fisiopatologia , Adulto , Ecocardiografia , Humanos , Hipertensão/sangue , Masculino , Valores de ReferênciaRESUMO
BACKGROUND: The present study was designed to evaluate the role of tachycardia-induced dynamic coronary artery diameter changes in the development of myocardial ischemia. METHODS: Coronary angiography at rest and during atrial pacing-induced myocardial ischemia was performed in 22 patients. The diameter of the proximal and the corresponding distal coronary artery segments at rest and during pacing was measured using quantitative coronary angiography. Plasma levels of noradrenaline, adrenaline, dopamine and endothelin were determined in a subset of 14 patients in blood drawn from aorta and coronary sinus at rest and during pacing. RESULTS: Luminal diameter in normal proximal and distal segments increased, respectively, from 2.93 +/- 0.34 and 1.40 +/- 0.04 mm at rest to 3.03 +/- 0.25 and 1.58 +/- 0.07 mm during atrial pacing. The diameter of the proximal coronary artery segments with significant concentric stenosis decreased from 1.28 +/- 0.4 mm at rest to 0.95 +/- 0.34 mm during pacing, whereas segments with either significant eccentric or non-significant stenosis did not change significantly. A correlation was found between the noradrenaline level in the coronary sinus and the distal coronary artery diameter. CONCLUSIONS: A decrease in diameter of coronary artery segments with concentric stenosis during tachycardia might contribute to the development of myocardial ischemia. Some of the dynamic coronary artery changes may be influenced by the plasma level of noradrenaline. No evidence was found to suggest that dynamic changes in the diameter of proximal segments are related to the changes in diameter of the corresponding distal segments.
Assuntos
Vasos Coronários/patologia , Vasos Coronários/fisiopatologia , Isquemia Miocárdica/patologia , Isquemia Miocárdica/fisiopatologia , Vasoconstrição , Adulto , Estimulação Cardíaca Artificial , Angiografia Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/sangue , Isquemia Miocárdica/diagnóstico por imagem , Estudos ProspectivosRESUMO
BACKGROUND: It can be assumed that endothelin (ET) the hitherto most powerful known vasoconstricting agent participates in the regulation of BP. The objective of this investigation was to compare ET plasma concentrations in different stages and types of arterial hypertension and to assess its possible participation in a rise of the BP. METHODS AND RESULTS: The authors assessed plasma concentration of ET1,2, using the RIA method, in 27 normotensive controls, 30 normotensive subjects with a family-history of hypertension, 21 patients with mild essential hypertension (EH), eight severe cases of EH and 27 patients with chronic renal failure who were in a regular dialyzation programe, incl. 13 treated on account of hypertension; in 14 the BP was within the normal range. The ET examination was supplemented by RIA assessment of the plasma renin activity (PRA). The authors recorded significantly higher ET concentrations as compared with controls (14.0 +/- 0.9 fmol/ml) in normotensive subjects from hypertensive families (18.1 +/- 1.2 fmol/ml), severe EH (26.1 +/- 3.2 fmol/l). Hypertensive patients with chronic renal failure (CHRS) had also higher ET levels (26.5 +/- 2.8 fmol/l). Patients with mild hypertension did not differ as regards ET concentrations (13.8 +/- 2.4 fmol/ml from controls. A significant increase of PRA was recorded in severe EH (3.4 +/- 1.2 ng/ml/hour) and in CHRS with hypertension (5.2 +/- 1.3 ng/ml/hour) as well as without hypertension (5.6 +/- 1.5 ng/ml/hour). CONCLUSIONS: The author's findings of elevated ET1,2 concentrations in subjects with a family disposition to hypertension, in advanced EH in renal hypertension and in CHRS support the assumption that ET can participate in the initial stages in the development and later in the progression of arterial hypertension either directly or by potentiating other pressor agents, e.g. higher activities of the renin-angiotensin system.
Assuntos
Endotelinas/sangue , Hipertensão/sangue , Adulto , Humanos , Hipertensão/fisiopatologia , Pessoa de Meia-Idade , Renina/sangueRESUMO
Arterial hypertension is nowadays no longer considered an isolated disorder of blood pressure regulation but a multifactorial disease with metabolic and cellular deviations. From the therapeutic aspect of thus conceived hypertension today inhibitors of the angiotensin converting enzyme seem most promising. With regard to their assumed comprehensive effect, the authors investigated simultaneously selected pressor and depressor humoral indicators and other indicators in 21 hypertensive patients with stage I and II of essential hypertension before and after three-month treatment with an angiotensin converting enzyme inhibitor lisinopril (Prinivil, Merck, Sharp and Dohme) and compared them with findings in 21 normotensive healthy subjects. Hypertensive subjects before treatment had, as compared with normotensives, significantly lower urinary kallikrein (7.8 +/- 1.2 < 18.0 +/- 4.2 EU/24hr, a significantly higher basal plasma adrenalin (1.27 +/- 0.20 > 0.54 +/- 0.20 pmol/ml) and adrenalin after a glucose load (1.26 +/- 0.22 > 0.51 +/- 0.12) and a higher relative plasma viscosity (1.74 +/- 0.02 > 1.67 +/- 0.01). The two groups did not differ significantly as to the plasma renin activity, plasma aldosterone and fibrinogen concentration and the level of urinary prostaglandins per 24 hr: 6-keto-prostaglandin F1a, thromboxane B2 and prostaglandins E and F2a. The 75 g glucose load produced an increased plasma renin, aldosterone and noradrenaline activity in normotensives as well as hypertensives before and after lisinopril treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Hipertensão/sangue , Lisinopril/uso terapêutico , Adulto , Aldosterona/sangue , Pressão Sanguínea/fisiologia , Catecolaminas/sangue , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Calicreínas/análise , Masculino , Pessoa de Meia-Idade , Renina/sangueRESUMO
Some metabolic and humoral deviations found in normotensive offspring from hypertensive families can be modified in the course of years either as a result of ageing or of the clinical manifestation of essential hypertension (EH). The authors compared therefore some metabolic indicators (blood sugar level, IRI, C-peptide and plasma lipids) and humoral factors (plasma catecholamines, renin activity, atrial natriuretic factor and endothelin) in four groups of subjects: 27 young normotensive sons from normotensive families (SNF) and 30 from hypertensive families (SHF) with the findings of normotonics (NT) (n = 21) and patients with EH (n = 21) by 15 years older. Despite a tendency towards higher blood sugar levels in SHF and EH, the basal as well as oGTT stimulated blood sugar values were within the normal range. They were, however, associated with higher IRI and C-peptide concentrations in SHF with a further increase in NT and a much higher increase in EH. This indicates that normal blood sugar homeostasis in these groups is achieved only by an increased insulin secretion. The reduction of the blood sugar/IRI ratio in older NT accentuated in EH, suggests an increasing insulin resistance. In the lipid spectrum the authors found an increase of total cholesterol with advancing age, this being most marked in EH where also a decline of HDL cholesterol was recorded. As to humoral factors, higher catecholamine concentrations were found in SHF. Their increase with advancing age was more marked in EH. The plasma renin activity declined with age in NT as well as in EH.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Hipertensão/metabolismo , Adulto , Glicemia/análise , Humanos , Hipertensão/genética , Resistência à Insulina , Lipídeos/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
To investigate the possible role of endothelin in coronary vasoconstriction contributing to the development of myocardial ischemia, plasma endothelin concentrations at rest and during atrial pacing-induced myocardial ischemia have been measured in blood samples drawn from the aorta and coronary sinus in 12 patients with significant narrowing of the left anterior descending coronary artery. The plasma endothelin concentrations at rest were similar in the aorta (AO/R) and coronary sinus (CS/R) (4.8 +/- 2.4 and 4.5 +/- 1.7 pg/ml, respectively), the difference between coronary sinus and aorta plasma endothelin concentration (CS/R-AO/R) being -0.3 +/- 1.7 pg/ml. During atrial pacing-induced myocardial ischemia aortic plasma endothelin concentration (AO/P) did not change (4.6 +/- 2.6 pg/ml) and only an insignificant increase in the plasma endothelin concentration in the coronary sinus (CS/P) was observed (5.3 +/- 2.8 pg/ml). The difference between coronary sinus and aortic endothelin plasma concentration (CS/P-AO/P) was 0.6 +/- 2.5 pg/ml. Finally, the difference in endothelin concentrations between coronary sinus and aorta rose only insignificantly during pacing as compared to the resting values ([CS/P-AO/P]-[CS/R-AP/R] being 0.9 +/- 3.2 pg/ml). Thus, atrial pacing-induced myocardial ischemia in patients with significant left anterior descending coronary artery stenosis was not accompanied by significant changes in coronary sinus plasma endothelin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Estimulação Cardíaca Artificial , Vasos Coronários , Endotelinas/sangue , Isquemia Miocárdica/sangue , Adulto , Idoso , Aorta , Endotelinas/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/fisiopatologia , Vasoconstrição/fisiologiaRESUMO
Hyperinsulinaemia and insulin resistance are associated with essential hypertension irrespective of obesity and non-insulin-dependent diabetes mellitus. One of the mechanisms whereby hyperinsulinaemia may play a role in the increase in blood pressure, is an increased activity of the sympathetic nervous system. The authors studied the incidence of hyperinsulinaemia, and the possibility of modulating it by 12-week administration of the ACE inhibitor (ACEI) lisinopril (Prinivil by MSD) at a dose of 20-40 mg/day. Compared with normotensive subjects, hypertensives showed a degree of hyperinsulinaemia and insulin resistance (higher blood glucose at higher immunoreactive insulin and C-peptide concentrations, and a higher IRI/blood glucose ratio) as well as manifestations of enhanced sympathetic activity (higher adrenaline levels). Lisinopril had a favourable effect not only on blood pressure but, also, on hyperinsulinaemia and adrenaline levels. It can be reasonably concluded that therapy with ACEI, in addition to its antihypertensive effect, may also favourably modulate some pathogenic and metabolic factors in essential hypertension.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Dipeptídeos/uso terapêutico , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Insulina/sangue , Adulto , Glicemia/análise , Pressão Sanguínea/efeitos dos fármacos , Peptídeo C/análise , Catecolaminas/sangue , Feminino , Humanos , Hipertensão/fisiopatologia , Lisinopril , Masculino , Pessoa de Meia-IdadeRESUMO
Plasma concentration of two main cardiovascular substances - atrial natriuretic factor (ANF) and endothelin - were studied in control subjects (n = 21) under basal conditions and 90 minutes after oral administration of glucose. In hypertensive patients (n = 21) these determinations were repeated after 12 weeks treatment with an angiotensin I-converting enzyme inhibitor lisinopril (Prinivil, Merck Sharp and Dohme). While basal and post-glucose ANF concentrations did not differ in controls and hypertensive patients, a tendency to the higher endothelin levels was found in our group of essential hypertension when compared to normotensive subjects. Glucose loading did not change significantly ANF concentrations in any studied group but significantly lowered plasma endothelin in both controls (from 13 +/- 0.95 to 9.50 +/- 0.95 fmol/ml) and hypertensive patients (from 15.05 +/- 1.23 to 12.15 +/- 1.03 fmol/min). Treatment of hypertensive patients with lisinopril paradoxically increased concentrations of ANF (from 6.43 +/- 2.53 to 11.47 +/- 4.90 fmol/ml) and lowered that of endothelin (from 15.05 +/- 1.23 to 12.17 +/- 1.58 fmol/ml). From our findings we may suggest that the relative predominance of the vasoconstrictor (endothelin) over the vasodilator (ANF) humoral substances might participate in pathogenesis of EH and that the reversal of this disadvantageous ratio after lisinopril (increase of ANF and decrease of endothelin) might contribute to the blood pressure reducing effect of ACEI. The drop in plasma endothelin after glucose remains so far unexplained consequence of glucose loading in both control and hypertensive subjects.
Assuntos
Fator Natriurético Atrial/sangue , Endotelinas/sangue , Hipertensão/sangue , Lisinopril/uso terapêutico , Adulto , Pressão Sanguínea/efeitos dos fármacos , Feminino , Teste de Tolerância a Glucose , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-IdadeRESUMO
Investigations in genetic forms of experimental hypertensions revealed certain haemodynamic, metabolic and humoral abnormalities in experimental animals already during the prehypertensive period. With regard to the obvious ratio of hereditary factors in the pathogenesis of human essential hypertension (EH), the objective of the present study was to test whether also in healthy normotensive subjects with a positive family history of EH some metabolic and humoral deviations can be detected, as compared with offspring from normotensive families. The authors compared therefore selected biochemical and humoral parameters in 20 sons of hypertensive parents (SH) with the findings in 20 sons from normotensive pa families (SN). SH had, as compared with SN, a significantly higher systolic BP (119 +/- 2.59 > 111.0 +/- +/- 2.04 mmHg). The trend of higher basal blood sugar levels 5.03 +/- 0.15 > 4.70 +/- 0.41 mmol/l) and the higher concentration of immunoreactive insulin (81.4 +/- 9.54 > 70.4 +/- after a glucose load +/- 7.78 microU/l) did not reach statistical significance. In SH plasma concentrations of adrenaline, noradrenaline and dopamine were significantly higher as well as the atrial natriuretic factor (11.7 +/- 0.77 > 8.4 +/- 0.40 fmol/ml) and of endothelin (18.2 +/- 1.70 > 12.7 +/- 0.87 fmol/ml). A load of 75 g glucose raised, as expected, the blood sugar level, IRI and C-peptide, but reduced unexpectedly the endothelin concentration in both groups. As to other biochemical parameters (fibrinogen, sodium, potassium, urea, creatinine, uric acid, cholesterol, HDL- and LDL-fractions, triacylglycerols), no significant differences were found between SH and SN. The finding of a raised mass of the left ventricle and certain differences in the diastolic and systolic left ventricular function are discussed in another paper. The results indicate that in young men with a positive family-history of EH already certain haemodynamic, metabolic and humoral deviations exist before clinical manifestation of hypertension which could contribute to later development of EH and its organ complications.