Eficácia e segurança da denervação renal por radiofrequência em pacientes com hipertensão resistente: uma meta-análise / Efficacy and safety of radiofrequency renal denervation in patients with resistant hypertension: a meta-analysis

INTRODUÇÃO: Diversos estudos foram publicados avaliando o uso da denervação renal por radiofrequência (DRR) no tratamento de pacientes com hipertensão arterial resistente (HAR). Essa técnica consiste em um procedimento minimamente invasivo que visa interromper a atividade dos nervosrenais via ablação. Entretanto,sua eficácia e segurança com cateter via radiofrequência ainda não foi elucidada. Essa meta-análise tem por objetivo investigar a eficácia da denervação renal por radiofrequência (DRR) comparado com sham ou anti hipertensivos. METODOLOGIA: Foi realizada uma busca nas bases de dados da PubMed, Embase e Cochrane, por ensaios clínicos randomizados que compararam a redução da pressão arterial entre a denervação renal por radiofrequência (DRR) e o sham ou tratamento padrão em pacientes com HAR. Os dados foram reunidos usando um modelo de efeito fixo, e os resultados foram dados em diferença de média (DM) e risco relativo (RR), com 95% de intervalo de confiança (IC). A heterogeneidade entre os estudos foi calculada pelo I2. Todas as estatísticas foram realizadas usando o R software(version 4.0.3). RESULTADOS: Ao todo foram incluídos 8 ensaios clínicos randomizados, composto por 934 pacientes (557 do grupo RDN e 377 do grupo controle). O seguimento dos estudos variou de 6 meses até 84 meses, a média de idade variou entre 53 a 64.5 anos e com 349 pacientes portadores de diabetes tipo 2. A DRR foi associada com redução significativa da pressão sistólica ambulatorial (DM: -6.25 mmHg, 95% IC: -8.83; -3.67, P< 0.001, I2= 52%), assim como na diastólica ambulatorial (DM: -2.67 mmHg, 95% IC: -4.38; -0.95, P=0.002, I2=50%) comparado com grupo controle. De maneira semelhante, houve redução significativa da pressão diastólica de consultório (DM: -5.11 mmHg, 95% IC: -9.19; -1.02, P=0.014, I2=72%). Não houve diferença estatística em relação à pressão sistólica de consultório (DM: -9.50 mmHg, 95% IC:-20.54; 1.54, P=0.092, I2=87%), aos efeitos adversos secundários (RR: 1.86, 95% IC: 0.66; 5.26, P=0.240, I2= 50%) e à crise hipertensiva (RR:1.10, 95% IC: 0.55; 2.22, P=0.780, I2=0%). CONCLUSÕES: Esta meta-análise demonstrou a eficácia do uso da DRR na redução da pressão arterial global ambulatorial e pressão diastólica de consultório, e não apresentou aumentos de efeitos adversos secundários e crise hipertensiva. Esses achados demonstram o potencial uso da DRR no tratamento de pacientes que possuem hipertensão arterial resistente.

Questionário H-5: um instrumento para o rastreio de crenças limitantes no paciente com hipertensão arterial / H-5 Questionnaire: an instrument for screening limiting beliefs in patients with arterial hypertension

INTRODUÇÃO E/OU FUNDAMENTO: Menos da metade dos pacientes com hipertensão arterial (HA) atinge sua meta terapêutica. A falta de adesão é apontada como a principal causa de resistência ao tratamento. Entre os motivos pelos quais os pacientes não aderem ao plano terapêutico, a falta de letramento em saúde, os mitos e as crenças limitantes (CLs) desempenham papel determinante. Reconhecer e reverter prontamente tais crenças pode ser decisivo para promover a adesão do paciente e o controle pressórico, mas faltam instrumentos que permitam esse rastreio de forma sistemática na prática clínica. MÉTODOS: Elaboramos um Questionário de cinco perguntas (H-5) a partir de análise exploratória das CLs mais frequentemente observadas em ambulatório de referência no tratamento da HA. Cada pergunta do H-5 explora um conjunto de CLs relativas a uma dimensão específica do tratamento anti-hipertensivo. O questionário foi aplicado a 30 pacientes com diagnóstico de HA resistente consecutivamente atendidos em ambulatório público de referência. As perguntas do H-5 são: 1. O que sentimos quando nossa pressão está alta?; 2. Qual o melhor momento para medir a pressão?; 3. Quando podemos parar de tomar o remédio da pressão?; 4. Porque a pressão alta é um problema?; 5. Qual dessas afirmações é verdadeira sobre o estilo de vida? O formato de avaliação foi por respostas fechadas de múltipla escolha, sendo oferecidas 4 opções por pergunta. RESULTADOS: O H-5 foi aplicado na sala de espera antes da consulta, com tempo médio de execução de 6 minutos. A idade média dos pacientes foi 63,9 ± 9,2 anos (sexo feminino: 83%: IMC: 33,1 ± 6,1). N de anti-hipertensivos: 3,9 ± 1,6; PAS media de consultório: 137 ± 17,4 mmHg); escolaridade: 80% apenas ensino fundamental. A Nota Média foi de 3 acertos em 5 (0= 5%; 2= 20%; 3= 50%; 4= 15%; 5=20%) A taxa de acertos por pergunta (P) foi respectivamente: P1= 20%; P2= 20%; P3= 95%; P4= 80%; P5=85%. Apenas 1 a cada 5 pacientes com HA resistente demonstrou saber que a HA é uma condição assintomática ou que a pressão arterial deve ser medida em condições controladas. CONCLUSÕES: A aplicação do Questionário H-5 foi simples e de rápida execução. 80% dos pacientes apresentou algum grau de crenças limitantes em relação ao tratamento da HA.

Androgenicity and venous endothelial function in post-menopausal women.

BACKGROUND: Endothelial dysfunction is one of the early signs of cardiovascular damage. High androgen levels have been related to inflammatory endothelial markers in pre- and post-menopausal women. AIM: This cross-sectional study aimed at investigating whether free androgen index (FAI) [estimated by dividing total testosterone (nmol/l) by SHBG (nmol/l) x 100] is related to endothelial function during post-menopause. SUBJECTS AND METHODS: Twenty-six post-menopausal women were assessed with the dorsal hand vein compliance technique. Acetylcholine (Ach) and sodium nitroprusside (SNP) dose-response curves were constructed to test endothelium-dependent and independent relaxation, respectively. RESULTS: Mean age was 54 yr (+/-4) and median time since menopause was 6 yr (interquartile range: 3-9). Patients were stratified according to FAI levels into two groups: FAI greater than or less than the group median of 2.5. Waist-to-hip ratio (WHR) was significantly higher in the group with FAI>2.5, as well as median dose of Ach for maximal vasodilation [720 (360-3600) ng/min with FAI>2.5 vs 36 (0.36-360) ng/min with FAI

Critical analysis of autoregressive and fast Fourier transform markers of cardiovascular variability in rats and humans

The autonomic nervous system plays an important role in physiological and pathological conditions, and has been extensively evaluated by parametric and non-parametric spectral analysis. To compare the results obtained with fast Fourier transform (FFT) and the autoregressive (AR) method, we performed a comprehensive comparative study using data from humans and rats during pharmacological blockade (in rats), a postural test (in humans), and in the hypertensive state (in both humans and rats). Although postural hypotension in humans induced an increase in normalized low-frequency (LFnu) of systolic blood pressure, the increase in the ratio was detected only by AR. In rats, AR and FFT analysis did not agree for LFnu and high frequency (HFnu) under basal conditions and after vagal blockade. The increase in the LF/HF ratio of the pulse interval, induced by methylatropine, was detected only by FFT. In hypertensive patients, changes in LF and HF for systolic blood pressure were observed only by AR; FFT was able to detect the reduction in both blood pressure variance and total power. In hypertensive rats, AR presented different values of variance and total power for systolic blood pressure. Moreover, AR and FFT presented discordant results for LF, LFnu, HF, LF/HF ratio, and total power for pulse interval. We provide evidence for disagreement in 23 percent of the indices of blood pressure and heart rate variability in humans and 67 percent discordance in rats when these variables are evaluated by AR and FFT under physiological and pathological conditions. The overall disagreement between AR and FFT in this study was 43 percent.

Critical analysis of autoregressive and fast Fourier transform markers of cardiovascular variability in rats and humans.

The autonomic nervous system plays an important role in physiological and pathological conditions, and has been extensively evaluated by parametric and non-parametric spectral analysis. To compare the results obtained with fast Fourier transform (FFT) and the autoregressive (AR) method, we performed a comprehensive comparative study using data from humans and rats during pharmacological blockade (in rats), a postural test (in humans), and in the hypertensive state (in both humans and rats). Although postural hypotension in humans induced an increase in normalized low-frequency (LFnu) of systolic blood pressure, the increase in the ratio was detected only by AR. In rats, AR and FFT analysis did not agree for LFnu and high frequency (HFnu) under basal conditions and after vagal blockade. The increase in the LF/HF ratio of the pulse interval, induced by methylatropine, was detected only by FFT. In hypertensive patients, changes in LF and HF for systolic blood pressure were observed only by AR; FFT was able to detect the reduction in both blood pressure variance and total power. In hypertensive rats, AR presented different values of variance and total power for systolic blood pressure. Moreover, AR and FFT presented discordant results for LF, LFnu, HF, LF/HF ratio, and total power for pulse interval. We provide evidence for disagreement in 23% of the indices of blood pressure and heart rate variability in humans and 67% discordance in rats when these variables are evaluated by AR and FFT under physiological and pathological conditions. The overall disagreement between AR and FFT in this study was 43%.

Increased sympathetic activity in normotensive offspring of malignant hypertensive parents compared to offspring of normotensive parents.

Malignant hypertension seems to be the consequence of very high blood pressure. Furthermore, an increase in sympathetic and renin-angiotensin system activity is considered to be the main mechanisms producing malignant hypertension. In the present study, 10 offspring of malignant hypertensive (OMH) parents (age 28 +/- 5 years, 7 males, 3 females, 2 white and 8 non-white) and 10 offspring of normotensive (ONT) parents (age 28 +/- 6 years, 2 males, 8 females, 3 white and 7 non-white) were evaluated. The OMH group had significantly higher (P < 0.05) casual blood pressure (125 +/- 10/81 +/- 5 mmHg) compared with ONT (99 +/- 13/67 +/- 5 mmHg). The increase in blood pressure was greater in OMH (Delta SBP = 17 +/- 2 vs Delta SBP = 9 +/- 1 mmHg in ONT) during cold pressor testing, but they had a lower increase in heart rate (Delta HR = 13 +/- 2 vs Delta HR = 20 +/- 3 bpm in ONT) during isometric exercise(handgrip test). Sympathetic activity, measured by microneurography, was significantly higher (P < 0.05) before exercise in OMH (17 +/- 6 vs 11 +/- 4 burst/min in ONT) and exhibited a greater increase (Delta = 18 +/- 10 vs Delta = 8 +/- 3 burst/min in ONT) during isometric exercise. This study showed increased sympathetic activity in OMH before exercise and a greater response during isometric exercise, suggesting an autonomic abnormality before exercise and a greater sympathetic response to physical stress in OMH compared to ONT.

Increased sympathetic activity in normotensive offspring of malignant hypertensive parents compared to offspring of normotensive parents

Malignant hypertension seems to be the consequence of very high blood pressure. Furthermore, an increase in sympathetic and renin-angiotensin system activity is considered to be the main mechanisms producing malignant hypertension. In the present study, 10 offspring of malignant hypertensive (OMH) parents (age 28 ± 5 years, 7 males, 3 females, 2 white and 8 non-white) and 10 offspring of normotensive (ONT) parents (age 28 ± 6 years, 2 males, 8 females, 3 white and 7 non-white) were evaluated. The OMH group had significantly higher (P < 0.05) casual blood pressure (125 ± 10/81 ± 5 mmHg) compared with ONT (99 ± 13/67 ± 5 mmHg). The increase in blood pressure was greater in OMH (Ä SBP = 17 ± 2 vs Ä SBP = 9 ± 1 mmHg in ONT) during cold pressor testing, but they had a lower increase in heart rate (Ä HR = 13 ± 2 vs Ä HR = 20 ± 3 bpm in ONT) during isometric exercise (handgrip test). Sympathetic activity, measured by microneurography, was significantly higher (P < 0.05) before exercise in OMH (17 ± 6 vs 11 ± 4 burst/min in ONT) and exhibited a greater increase (Ä = 18 ± 10 vs Ä = 8 ± 3 burst/min in ONT) during isometric exercise. This study showed increased sympathetic activity in OMH before exercise and a greater response during isometric exercise, suggesting an autonomic abnormality before exercise and a greater sympathetic response to physical stress in OMH compared to ONT.

Influence of cardiopulmonary reflex on the sympathetic activity during myocardial infarction.

The time-course of changes in renal sympathetic nerve activity (RSNA), arterial and cardiopulmonary baroreflexes sensitivities was evaluated in conscious rats eight hours (8 h) and ten days (10 day) after myocardial infarction (MI), induced by coronary artery ligation. RSNA was recorded by a platinum electrode implanted in left renal nerve. Arterial and cardiopulmonary baroreflexes sensitivities were evaluated by changes in blood pressure and serotonin administration, respectively. Both 8 h and 10 day groups presented hypotension (103+/-4 vs. 102+/-2 vs. 115+/-4 mm Hg), but only 8 h showed tachycardia (422+/-22 vs. 378+/-11 vs. 384+/-9 bpm) when compared to Control rats. RSNA was depressed 8 h after MI and increased in 10 day group (12+/-2 vs. 39+/-8 vs. 22+/-2 mV/cycle). Although arterial baroreflex control of heart rate was similar in all groups, the arterial baroreflex control of RSNA in 8 h group was impaired during reductions (-0.35+/-0.10 vs. -1.66+/-0.23 vs. -0.09+/-0.14 mV/cycle/mm Hg) or increases (-0.77+/-0.17 vs. -1.63+/-0.58 vs. -1.66+/-0.17 mV/cycle/mm Hg) in blood pressure when compared to Control animals. Moreover, cardiopulmonary baroreflex bradycardic response was increased in 8 h rats and normalized in 10 day group. The results suggest that the increased cardiopulmonary baroreflex sensitivity in 8 h may contribute to the reduction in the tonic level of RSNA as well as in the impairment of the baroreflex control of RSNA in the presence of hypotension.

Pressure and time dependence of the cardiopulmonary reflex response in patients with hypertensive cardiomyopathy.

The first minutes of the time course of cardiopulmonary reflex control evoked by lower body negative pressure (LBNP) in patients with hypertensive cardiomyopathy have not been investigated in detail. We studied 15 hypertensive patients with left ventricular dysfunction (LVD) and 15 matched normal controls to observe the time course response of the forearm vascular resistance (FVR) during 3 min of LBNP at -10, -15, and -40 mmHg in unloading the cardiopulmonary receptors. Analysis of the average of 3-min intervals of FVR showed a blunted response of the LVD patients at -10 mmHg (P = 0.03), but a similar response in both groups at -15 and -40 mmHg. However, using a minute-to-minute analysis of the FVR at -15 and -40 mmHg, we observed a similar response in both groups at the 1st min, but a marked decrease of FVR in the LVD group at the 3rd min of LBNP at -15 mmHg (P = 0.017), and -40 mmHg (P = 0.004). Plasma norepinephrine levels were analyzed as another neurohumoral measurement of cardiopulmonary receptor response to LBNP, and showed a blunted response in the LVD group at -10 (P = 0.013), -15 (P = 0.032) and -40 mmHg (P = 0.004). We concluded that the cardiopulmonary reflex response in patients with hypertensive cardiomyopathy is blunted at lower levels of LBNP. However, at higher levels, the cardiopulmonary reflex has a normal initial response that decreases progressively with time. As a consequence of the time-dependent response, the cardiopulmonary reflex response should be measured over small intervals of time in clinical studies.

Pressure and time dependence of the cardiopulmonary reflex response in patients with hypertensive cardiomyopathy

The first minutes of the time course of cardiopulmonary reflex control evoked by lower body negative pressure (LBNP) in patients with hypertensive cardiomyopathy have not been investigated in detail. We studied 15 hypertensive patients with left ventricular dysfunction (LVD) and 15 matched normal controls to observe the time course response of the forearm vascular resistance (FVR) during 3 min of LBNP at -10, -15, and -40 mmHg in unloading the cardiopulmonary receptors. Analysis of the average of 3-min intervals of FVR showed a blunted response of the LVD patients at -10 mmHg (P = 0.03), but a similar response in both groups at -15 and -40 mmHg. However, using a minute-to-minute analysis of the FVR at -15 and -40 mmHg, we observed a similar response in both groups at the 1st min, but a marked decrease of FVR in the LVD group at the 3rd min of LBNP at -15 mmHg (P = 0.017), and -40 mmHg (P = 0.004). Plasma norepinephrine levels were analyzed as another neurohumoral measurement of cardiopulmonary receptor response to LBNP, and showed a blunted response in the LVD group at -10 (P = 0.013), -15 (P = 0.032) and -40 mmHg (P = 0.004). We concluded that the cardiopulmonary reflex response in patients with hypertensive cardiomyopathy is blunted at lower levels of LBNP. However, at higher levels, the cardiopulmonary reflex has a normal initial response that decreases progressively with time. As a consequence of the time-dependent response, the cardiopulmonary reflex response should be measured over small intervals of time in clinical studies.

Dysregulation of peripheral and central chemoreflex responses in Chagas' heart disease patients without heart failure.

BACKGROUND: The peripheral and central chemoreflexes are important autonomic mechanisms for regulating breathing and cardiovascular function. Although pathological inflammatory infiltration of the peripheral chemoreceptors and central nervous system has been reported in Chagas' disease, functional evaluation of chemoreflexes has not yet been performed. METHODS AND RESULTS: The hypothesis that chemoreflex function is altered in patients with Chagas' heart disease (CH) but normal left ventricle function was tested in 12 CH patients and 13 matched control subjects. The ventilatory rate, minute ventilation, heart rate, mean arterial pressure, forearm blood flow, forearm vascular resistance, and venous norepi-nephrine responses to hypoxia and hypercapnia were determined. During hypoxia, the decrease in oxygen saturation was smaller in CH patients, despite a similar ventilatory response between groups. Both groups showed an increase in heart rate during hypoxia, but this response was blunted in CH patients. Although the mean arterial pressure response to hypoxia was similar in both groups, forearm vascular resistance significantly decreased in control subjects while remaining unchanged in CH patients. Moreover, a significant increase in plasma norepinephrine levels elicited by stimulation of peripheral chemoreceptors was observed only in the CH group. During hypercapnia, the increase in minute ventilation was smaller in CH patients, who did not exhibit the increase in norepinephrine observed in control subjects. CONCLUSIONS: These data suggest that CH potentiates respiratory, cardiovascular, and autonomic responses to peripheral chemoreceptor activation by hypoxia in patients with normal left ventricular function. The ventilatory and sympathetic responses to central chemoreceptor activation by hypercapnia, however, are significantly blunted.

Hormonal and cardiovascular reflex assessment in a female patient with pure autonomic failure.

We report the case of a 72-year-old female with pure autonomic failure, a rare entity, whose diagnosis of autonomic dysfunction was determined with a series of complementary tests. For approximately 2 years, the patient has been experiencing dizziness and a tendency to fall, a significant weight loss, generalized weakness, dysphagia, intestinal constipation, blurred vision, dry mouth, and changes in her voice. She underwent clinical assessment and laboratory tests (biochemical tests, chest X-ray, digestive endoscopy, colonoscopy, chest computed tomography, abdomen and pelvis computed tomography, abdominal ultrasound, and ambulatory blood pressure monitoring). Measurements of catecholamine and plasmatic renin activity were performed at rest and after physical exercise. Finally the patient underwent physiological and pharmacological autonomic tests that better diagnosed dysautonomia.

Autonomic abnormalities demonstrable in young normotensive subjects who are children of hypertensive parents.

Although a slightly elevated office blood pressure (BP) has been reported in several studies, little is known about the prolonged resting blood pressure, heart rate (HR) and baroreflex sensitivity (BRS) of prehypertensive subjects with a family history of hypertension. Office blood pressure, prolonged resting (1 h) BP and HR were measured in 25 young normotensives with a positive family history of hypertension (FH+) and 25 young normotensives with a negative family history of hypertension (FH-), matched for age, sex, and body mass index. After BP and HR measurements, blood samples were collected for the determination of norepinephrine, plasma renin activity and aldosterone levels, and baroreflex sensitivity was then tested. Casual BP, prolonged resting BP and heart rate were significantly higher in the FH+ group (119.9 +/- 11.7/78.5 +/- 8.6 mmHg, 137.3 +/- 12.3/74.4 +/- 7.9 mmHg, 68.5 +/- 8.4 bpm) compared to the FH- group (112.9 +/- 11.4/71.2 +/- 8.3 mmHg, 128.0 +/- 11. 8/66.5 +/- 7.4 mmHg, 62.1 +/- 6.0 bpm). Plasma norepinephrine level was significantly higher in the FH+ group (220.1 +/- 104.5 pg/ml) than in the FH- group (169.1 +/- 63.3 pg/ml). Baroreflex sensitivity to tachycardia (0.7 +/- 0.3 vs 1.0 +/- 0.5 bpm/mmHg) was depressed in the FH+ group (P<0.05). The FH+ group exhibited higher casual blood pressure, prolonged resting blood pressure, heart rate and plasma norepinephrine levels than the FH- group (P<0.05), suggesting an increased sympathetic tone in these subjects. The reflex tachycardia was depressed in the FH+ group.

Decreased cardiopulmonary baroreflex sensitivity in Chagas' heart disease.

No study has been performed on reflexes originating from receptors in the heart that might be involved in the pathological lesions of Chagas' heart disease. Our study was undertaken to analyze the role of cardiopulmonary reflex on cardiovascular control in Chagas' disease. We studied 14 patients with Chagas' disease without heart failure and 12 healthy matched volunteers. Central venous pressure, arterial blood pressure, heart rate, forearm blood flow, and forearm vascular resistance were recorded during deactivation of cardiopulmonary receptors. By reducing central venous pressure by applying -10 and -15 mm Hg of negative pressure to the lower body, we observed (a) a similar decrease of central venous pressure in both groups; (b) a marked increase in forearm vascular resistance in the control group but a blunted increase in the Chagas' group; and (c) no significant changes in blood pressure and heart rate. To analyze cardiopulmonary and arterial receptors, we applied -40 mm Hg of lower-body negative pressure. As a consequence, (a) central venous pressure decreased similarly in both groups; (b) blood pressure was maintained in the control group, whereas in patients with Chagas' disease, a decrease in systolic and mean arterial pressure occurred; (c) heart rate increased in both groups; and (d) forearm vascular resistance increased significantly and similarly in both groups. Unloading of receptors with low levels of lower-body negative pressure did not increase forearm vascular resistance in patients with Chagas' disease, which suggests that the reflex mediated by cardiopulmonary receptors is impaired in patients with Chagas' disease without heart failure. Overall control of circulation appears to be compromised because patients did not maintain blood pressure under high levels of lower-body negative pressure.

Autonomic abnormalities demonstrable in young normotensive subjects who are children of hypertensive parents

Although a slightly elevated office blood pressure (BP) has been reported in several studies, little is known about the prolonged resting blood pressure, heart rate (HR) and baroreflex sensitivity (BRS) of prehypertensive subjects with a family history of hypertension. Office blood pressure, prolonged resting (1 h) BP and HR were measured in 25 young normotensives with a positive family history of hypertension (FH+) and 25 young normotensives with a negative family history of hypertension (FH-), matched for age, sex, and body mass index. After BP and HR measurements, blood samples were collected for the determination of norepinephrine, plasma renin activity and aldosterone levels, and baroreflex sensitivity was then tested. Casual BP, prolonged resting BP and heart rate were significantly higher in the FH+ group (119.9 + or - 11.7/78.5 + or - 8.6 mmHg, 137.3 + or - 12.3/74.4 + or - 7.9 mmHg, 68.5 + or - 8.4 bpm) compared to the FH- group (112.9 + or - 11.4/71.2 + or - 8.3 mmHg, 128.0 + or - 11.8/66.5 + or - 7.4 mmHg, 62.1 + or - 6.0 bpm). Plasma norepinephrine level was significantly higher in the FH+ group (220.1 + or - 104.5 pg/ml) than in the FH- group (169.1 + or - 63.3 pg/ml). Baroreflex sensitivity to tachycardia (0.7 + or - 0.3 vs 1.0 + or - 0.5 bpm/mmHg) was depressed in the FH+ group (P<0.05). The FH+ group exhibited higher casual blood pressure, prolonged resting blood pressure, heart rate and plasma norepinephrine levels than the FH- group (P<0.05), suggesting an increased sympathetic tone in these subjects. The reflex tachycardia was depressed in the FH+ group

Cardiopulmonary reflex impairment in experimental diabetes in rats.

The aim of the present study was to evaluate the sensitivity of the cardiopulmonary receptors in experimental diabetes induced by streptozotocin by the use of 2 different methods: (1) administration of increasing doses of serotonin to analyze peak changes of arterial pressure and heart rate for each given dose in conscious intact normal and diabetic rats; (2) expanding blood volume with the use of dextran (6%) to produce similar increases in left ventricular end-diastolic pressure to quantify the arterial pressure, heart rate, and renal sympathetic nerve activity in sinoaortic, denervated, anesthetized normal and diabetic rats. Blood samples were collected to measure blood glucose. Diabetic rats showed hyperglycemia (22+/-0. 7 versus 7+/-0.2 mmol/L), reduced body weight (226+/-12 versus 260+/-4 g) and heart rate (294+/-14 versus 350+/-10 bpm), and similar arterial pressure (104+/-4 versus 113+/-4 mm Hg) when compared with control rats. Serotonin induced significant bradycardia and hypotension, which were similar and proportional to the dose injected in both groups. Mean arterial pressure and heart rate decreases in response to volume overload were significantly lower in diabetic than in control rats. The reflex reduction of the renal sympathetic nerve activity as expressed by percentage changes in nerve activity in response to increasing left end-diastolic pressure was abolished in diabetic animals (1.9+/-0.8% versus -14+/-4%/mm Hg in controls). These results showed an impairment of cardiopulmonary reflex control of circulation in diabetes during acute volume expansion. The normal responses to serotonin administration indicated that the cardiopulmonary reflex is still preserved in diabetic rats.

Lipid metabolism alterations in normotensive subjects with positive family history of hypertension.

Metabolic abnormalities are usually reported in hypertensive patients. These metabolic alterations seem to begin in childhood. The young offspring of hypertensive parents have not been studied thoroughly for metabolic alterations. The aim of this study was to examine the level of total cholesterol, LDL cholesterol, VLDL cholesterol, HDL cholesterol, uric acid, glycemia, aldosterone, and plasma renin activity in a population of 42 young, slender normotensive subjects with positive family history of hypertension (FH+) or negative family history of hypertension (FH-). Measurements were made in 20 young normotensive subjects (age 21.1+/-2.2 years, 11 males, 15 white, 5 oriental, body mass index of 22.1+/-2.3 kg/m2) with FH+ and 22 young normotensive subjects (age 19.9+/-1.4 years, 17 males, 17 white, 5 oriental, body mass index of 22.1+/-2.3 kg/m2) with FH-. The total cholesterol (4.47+/-0.8 versus 3.95+/-0.6 mmol/L), LDL cholesterol (2.74+/-0.63 versus 2.36+/-0.61 mmol/L), VLDL cholesterol (0.5+/-0.25 versus 0.35+/-0.09 mmol/L), and triglycerides (2.52+/-1.26 versus 1.76+/-0.5 mmol/L) were significantly elevated (P<.05) in the FH+ group compared with the FH- group. The total cholesterol/HDL cholesterol ratio was significantly higher in the group with a positive family history of hypertension (3.75+/-0.02 versus 3.11+/-0.02, P<.05). Glycemia was slightly elevated in the FH+ group (2.16+/-0.29 mmol/L) but was not significantly different from that of the FH- group (2+/-0.2 mmol/L). Uric acid, plasma renin activity, and aldosterone were similar in both groups. We conclude that young, slender normotensive subjects with a positive history of hypertension show alterations in lipid metabolism, suggesting a positive correlation between lipid metabolism and hypertension heredity.