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1.
J Hum Hypertens ; 22(11): 761-6, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18509343

RESUMEN

Dependence of the ambulatory arterial stiffness index (AASI) on data scattering interferes with its potential clinical relevance. We assessed the correlates and all-cause mortality associations of a modified AASI (s-AASI). AASI was derived from the 24-h diastolic vs. systolic blood pressure linear regression line, whereas s-AASI was derived by symmetric regression (bisecting the line of diastolic vs systolic and systolic vs. diastolic). Of 2918 patients 55% were women; age was 56 +/- 16 years and body mass index was 27.3 +/- 4.5 kg/m(2). Average 24-h ambulatory blood pressure was 138 +/- 16/78 +/- 10 mm Hg. Applying the modified method for calculating AASI yielded a different measure: the negative correlation between AASI and blood pressure dipping (r = -0.304, P < 0.0001) was abolished (r = +0.223, P < 0.0001), s-AASI was more dependent on age (r = 0.266 vs. r = 0.089 for AASI), and prediction of all-cause mortality was enhanced; hazard ratio (95% confidence intervals) 1.17 (1.00-1.36) per 1 s.d. increase in s-AASI in the fully adjusted model as compared with 1.15 (0.97-1.36) for AASI.


Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial/métodos , Presión Sanguínea/fisiología , Hipertensión/mortalidad , Resistencia Vascular/fisiología , Causas de Muerte/tendencias , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/fisiopatología , Israel/epidemiología , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias
2.
J Hum Hypertens ; 19(7): 565-7, 2005 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15829998

RESUMEN

The European Society of Hypertension (ESH) has issued guidelines for the detection and treatment of hypertension. According to these guidelines, normal 24-h ambulatory blood pressure (ABP) is defined as lower than 125/80 mmHg. Another publication of ESH recommendations for blood pressure (BP) measurement defines normal awake and asleep blood pressure as lower than 135/85 and 120/70 mmHg, respectively. Our aim was to investigate the compatibility of these two recently proposed ABP cutoffs in clinical practice. We analysed 1495 consecutive ABP measurements. In all, 56% of the subjects were female; age 58 +/- 16 years; body mass index 27 +/- 4 kg/m(2); clinic BP 151+/-22/84 +/- 13 mmHg. Two-thirds were treated for hypertension, and 11% for diabetes. Subjects were classified as having normal 24-h BP if the corresponding value was <125/80 mmHg. Normal awake-sleep BP was diagnosed if awake BP was <135/85 mmHg and sleep BP was <120/70 mmHg. Concordance between the cutoffs was found in 93% of the subjects. Among the 7% discordant subjects, 4.5% were hypertensive applying the 24 h, but not awake-sleep, BP values, whereas only 2.5% were hypertensive according to awake-sleep, but not 24 h, BP values (P < 0.005). In Conclusion, in real-life ABP measurement, a good agreement was found between two recently issued ABP normality definitions. However, some subjects are classified as hypertensive only according to one of these methods, more often by the 24-h cutoff of 125/80. This discordance may be significant in large-scale clinical BP monitoring.


Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial/instrumentación , Monitores de Presión Sanguínea/normas , Presión Sanguínea/fisiología , Ritmo Circadiano/fisiología , Guías de Práctica Clínica como Asunto , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados
3.
Hypertension ; 23(6 Pt 2): 1051-3, 1994 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8206592

RESUMEN

We assessed the effect of the vasodilating calcium channel blocker nitrendipine on glucose tolerance in young spontaneously hypertensive rats (SHR) (n = 15). The nitrendipine group received 1 g/kg chow for 3 weeks. Untreated SHR (n = 14) served as controls. At 3 weeks body weight was comparable, whereas systolic blood pressure was 157 +/- 9 mm Hg in nitrendipine-treated rats versus 191 +/- 10 mm Hg in controls (mean +/- SD, P < .00001). Fasting glucose was 6.8 +/- 2.7 mmol/L in nitrendipine-treated versus 8.9 +/- 1.5 mmol/L in control rats (P < .03). An intravenous glucose tolerance test (300 mg/kg) showed plasma glucose levels at 2, 5, 15, and 30 minutes to be significantly lower in the nitrendipine-treated group versus controls (two-way ANOVA, P < .03). Glucose utilization was estimated by the uptake of [3H]deoxyglucose after its intravenous administration (2 microCi/100 g body wt) to instrumented awake animals. Heart and striated muscle uptake was, respectively, 7983 +/- 5812 and 951 +/- 731 cpm.microL/g.min in the nitrendipine-treated group versus 3532 +/- 2316 and 424 +/- 201 cpm.microL/g.min in controls (P < .02 and P < .04, respectively). [3H]Deoxyglucose plasma half-life and fasting and post-glucose load insulin levels were comparable in the two groups. The results show that nitrendipine improves glucose tolerance by increasing muscle glucose uptake. We suggest that glucose tolerance in SHR is influenced by muscle blood flow and can be improved by vasodilation.


Asunto(s)
Desoxiglucosa/farmacocinética , Glucosa/fisiología , Hipertensión/fisiopatología , Nitrendipino/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Prueba de Tolerancia a la Glucosa , Hipertensión/metabolismo , Resistencia a la Insulina , Músculos/irrigación sanguínea , Ratas , Ratas Endogámicas SHR , Flujo Sanguíneo Regional/efectos de los fármacos
4.
Hypertension ; 7(5): 729-33, 1985.
Artículo en Inglés | MEDLINE | ID: mdl-2993163

RESUMEN

Material extracted and partially purified from plasma of the Sabra hypertension prone rats was found to be capable of 1) inhibiting the binding of 3H-ouabain to rat brain synaptosomes, 2) inhibiting the activity of rat brain microsomal Na, K activated adenosine triphosphatase, and 3) increasing the contractile force of rat heart muscle. The results demonstrate the presence of a ouabainlike compound in the plasma of these rats. The plasma concentration of this compound in Sabra hypertension prone rats was 698 +/- 199 nmol/ml in ouabain equivalents (SEM; n = 11) versus 2543 +/- 1140 nmol/ml (n = 9) in the Sabra normotensive strain. The presence of ouabainlike compound in the plasma is consistent with the hypothesis that this compound functions as a hormone that regulates Na, K activated adenosine triphosphatase activity and the physiological processes in which this enzyme is involved.


Asunto(s)
Hipertensión/sangre , Ouabaína/sangre , Animales , Cromatografía Líquida de Alta Presión , Masculino , Contracción Miocárdica/efectos de los fármacos , Ouabaína/farmacología , Ratas , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Tritio
5.
J Hypertens ; 11(6): 605-9, 1993 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8397239

RESUMEN

OBJECTIVE: To investigate whether the reported insulin-like properties of vanadate may have hypertensinogenic actions in Sabra rats. DESIGN: Comparison of [3H]-deoxyglucose muscle uptake as well as blood pressure and its response to acute volume expansion and pressors infusions in 16 vanadate-treated (VT) and 12 control rats. METHODS: Rats drank either tap water or 0.2 g/l vanadate for 4 weeks. A trace amount of [3H]-deoxyglucose was administered intravenously to evaluate its plasma half-life and tissue uptake. Intra-arterial blood pressure was recorded in response to acute intravenous saline (4 ml/100 g body weight) and to incremental bolus injections of noradrenaline and angiotensin II (Ang II). RESULTS: Skeletal muscle uptake of [3H]-deoxyglucose was significantly higher in VT than in control rats. There was no difference between the blood pressure of VT or control rats; however, 2 h after saline loading the mean intra-arterial blood pressure was significantly higher in VT than in control rats. The Ang II-induced blood pressure rise was also significantly higher in VT rats. CONCLUSION: The insulin-like activity of vanadate may be associated with salt-sensitive hypertension.


Asunto(s)
Hipertensión/inducido químicamente , Insulina/farmacología , Cloruro de Sodio/farmacología , Vanadatos/farmacología , Animales , Desoxiglucosa/farmacocinética , Masculino , Músculos/metabolismo , Ratas
6.
J Hypertens ; 11(7): 703-7, 1993 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8228188

RESUMEN

OBJECTIVE: To study the effects of chronic insulin administration without sugar supplementation on blood pressure and response to acute saline loading in normal rats. DESIGN: Comparison of blood pressure, insulin and glucose levels in 24 insulin-treated and 12 control rats on regular rat chow (not supplemented with sugar). METHODS: Sustained-release insulin implants (or sham implantation for the control rats) were administered subcutaneously. The sustained-release insulin implant size was gradually increased. Tail-cuff systolic blood pressure, insulin and glucose were measured twice a week for 8 weeks, after which intra-arterial blood pressure was recorded under resting conditions and 2 h after saline loading in seven insulin-treated and seven control rats. RESULTS: Insulin-treated rats had a 1.2- to twofold increase in insulin without hypoglycaemia, a small but significant increase in glucose levels being found at weeks 6 and 8. When the rats were killed (week 8) triglyceride and fructosamine levels were increased in the insulin-treated rats in comparison with controls. Neither tail-cuff systolic blood pressure nor resting intra-arterial blood pressure differed between the two groups. However, acute saline loading resulted in significantly higher blood pressure in the insulin-treated rats, without altering renal Na+ excretion. CONCLUSIONS: It is possible to produce mild hyperinsulinaemia without hypoglycaemia by gradually increasing subcutaneous sustained-release insulin administration without sugar supplementation. Such hyperinsulinaemia is associated with significantly higher glucose, fructosamine and triglyceride levels, and normal tail-cuff and resting intra-arterial blood pressure. Insulin may induce intolerance to acute volume loading that is not associated with Na+ retention.


Asunto(s)
Presión Sanguínea , Insulina/farmacología , Cloruro de Sodio/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Carbohidratos/farmacología , Implantes de Medicamentos , Hipertensión/fisiopatología , Masculino , Ratas , Ratas Endogámicas , Descanso , Factores de Tiempo
7.
J Hypertens ; 11(10): 1121-5, 1993 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8258677

RESUMEN

OBJECTIVE: To assess the relationship of insulin levels and glucose tolerance to blood pressure in hypertension. DESIGN: An open, prospective trial of exercise training with ambulatory blood pressure monitoring and intravenous glucose tolerance testing before and after a 14-week training programme. PATIENTS: Twenty sedentary, untreated, non-obese, normoglycaemic individuals of both sexes with uncomplicated essential hypertension, of whom 16 completed the study. INTERVENTION: Fourteen weeks of supervised, low-intensity, group exercise of three 1-h sessions per week. MAIN OUTCOME MEASURES: Ambulatory and clinic blood pressure, and glucose and insulin responses to an intravenous glucose tolerance test. RESULTS: Maximal work capacity on a bicycle ergometer increased by 20% (P < 0.001); 24-h ambulatory blood pressure was 143 +/- 12/87 +/- 5 mmHg before and 142 +/- 13/87 +/- 7 mmHg after training. Clinic blood pressure decreased from 166 +/- 14/103 +/- 5 mmHg to 157 +/- 12/99 +/- 6 mmHg (P < 0.03). Two-way analysis of variance indicated significant decreases in both glucose (P < 0.04) and insulin (P < 0.03), fasting and throughout the intravenous glucose tolerance test. CONCLUSIONS: Although mild exercise reduced clinic blood pressure significantly, it did not affect ambulatory blood pressure despite a marked reduction in glucose and insulin levels. This finding argues against a determinant role of insulin in the 24-h maintenance of blood pressure in hypertensive patients under the conditions of the study.


Asunto(s)
Glucemia/metabolismo , Presión Sanguínea , Hipertensión/fisiopatología , Insulina/sangre , Educación y Entrenamiento Físico , Adulto , Atención Ambulatoria , Análisis de Varianza , Determinación de la Presión Sanguínea/métodos , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Hipertensión/sangre , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Estudios Prospectivos
8.
J Hypertens ; 1(1): 53-6, 1983 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-6099380

RESUMEN

The activity of renal Na-K-ATPase was compared in hypertension-prone (SBH) and hypertension-resistant (SBN) Sabra rats on regular sodium intake and 2-3 weeks after a high sodium diet. ATPase activity was determined in single nephron segments by a micromethod. The activity profile was found to be similar in the two substrains on both regimens. Following high sodium intake there was a significant increment of Na-K-ATPase activity which was limited to the medullary thick ascending limb in the two substrains. The results clearly indicate a lack of relationship between renal Na-K-ATPase activity and proneness or resistance to hypertension in this experimental model.


Asunto(s)
Hipertensión/enzimología , Nefronas/enzimología , ATPasa Intercambiadora de Sodio-Potasio/análisis , Animales , Masculino , Ratas , Ratas Endogámicas , Sodio/administración & dosificación
9.
Am J Hypertens ; 7(3): 217-21, 1994 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-8003271

RESUMEN

A prospective analysis of consecutive ambulatory blood pressure monitorings over a 5 month period identified 50 subjects (35%) who took an afternoon nap during the monitoring. The average duration of daytime sleep, as reported by the patients, was 1.8 +/- 0.6 h compared with the reported 7 +/- 2 h for nighttime sleep. Ambulatory blood pressure values during daytime awake periods were significantly higher compared with daytime sleep and nighttime sleep. The blood pressure decline during daytime sleep and nighttime sleep was similar. The pattern of blood pressure changes during daytime sleep was comparable in normotensive (n = 16), untreated (n = 10), and treated hypertensives (n = 24), irrespective of age, gender, and the level of blood pressure. The marked decline in blood pressure during daytime sleep suggests that sleep itself, rather than an endogenous circadian rhythm, is responsible for the blood pressure dip observed during both daytime sleep and nighttime sleep. Ignoring actual sleeping time in people who sleep during the day may greatly distort the day-night ambulatory blood pressure difference, when the latter is calculated on the basis of arbitrarily defined "day" and "night" periods.


Asunto(s)
Presión Sanguínea/fisiología , Sueño/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Monitores de Presión Sanguínea , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Prospectivos
10.
Am J Hypertens ; 10(6): 683-6, 1997 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9194516

RESUMEN

This study was conducted to test the hypothesis that acute, widespread N-nitro-L-arginine methyl ester (L-NAME) induced vasoconstriction and hypertension may affect glucose tolerance and insulin sensitivity in normal rats. Comparisons were made of blood pressure, intravenous glucose tolerance, and insulin response and [3H]-deoxyglucose tissue uptake between L-NAME and control treated rats. Chronically instrumented, awake rats were administered L-NAME (30 mg/kg) (n = 8) or saline (0.3 mL) (n = 8) intravenously. After blood pressure stabilized, a bolus injection containing glucose (300 mg/kg) and trace [3H]-deoxyglucose was administered. Arterial blood was sampled for evaluation of glucose tolerance, insulin response, and [3H]-deoxyglucose muscle uptake. L-NAME treated rats had a persistent 54 +/- 4 mm Hg blood pressure rise while fasting, and postload plasma glucose and insulin responses did not differ, nor did heart and striated muscle [3H]-deoxyglucose uptake differ. In conclusion, acute L-NAME induced hypertension does not result in glucose intolerance, hyperinsulinemia, or decreased [3H]-deoxyglucose muscle uptake.


Asunto(s)
Desoxiglucosa/metabolismo , Glucosa/metabolismo , Hipertensión/metabolismo , Insulina/metabolismo , NG-Nitroarginina Metil Éster , Animales , Prueba de Tolerancia a la Glucosa , Hipertensión/inducido químicamente , Hipertensión/fisiopatología , Músculo Esquelético/metabolismo , Ratas , Ratas Sprague-Dawley
11.
Am J Hypertens ; 3(2): 136-9, 1990 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-2137702

RESUMEN

Systemic and regional hemodynamics were studied in DOCA-treated Sabra hypertensive (SBH) and normotensive (SBN) rats. In SBH rats, mean arterial pressure (MAP) and total peripheral resistance index (TPRI) increased significantly. In SBN rats, MAP remained stable and TPRI decreased. Cardiac output and heart rate were unchanged. Opposed changes in TPRI were mediated mainly by changes in vascular resistance of the skin, skeletal muscles and splanchnic organs. Both strains developed significant biventricular hypertrophy. We conclude that SBH and SBN rats' susceptibility or resistance to DOCA-salt hypertension are associated with opposed changes in TPRI. The development of biventricular hypertrophy is apparently dissociated from systemic hemodynamic changes.


Asunto(s)
Cardiomegalia/fisiopatología , Desoxicorticosterona/efectos adversos , Hemodinámica/efectos de los fármacos , Cloruro de Sodio/efectos adversos , Animales , Presión Sanguínea/efectos de los fármacos , Cardiomegalia/inducido químicamente , Cardiomegalia/etiología , Circulación Coronaria/efectos de los fármacos , Hipertensión/inducido químicamente , Hipertensión/complicaciones , Hipertensión/fisiopatología , Masculino , Ratas , Ratas Endogámicas , Flujo Sanguíneo Regional/efectos de los fármacos , Resistencia Vascular/efectos de los fármacos
12.
Am J Hypertens ; 14(12): 1211-8, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11775129

RESUMEN

To examine the role of insulin-like growth factor-1 (IGF-1) in renal atrophy of rats with two-kidney, one-clip (2K1C), in which the clipped kidney atrophies, and in the one-kidney, one-clip (IK1C) model of renovascular hypertension, in which it hypertrophies, we studied levels of IGF-I, mRNA, and protein in 2K1C, IK1C, and unilateral nephrectomy (NPX) in rats by solution-hybridization RNase protection, and radioimmunoassay, respectively, both cross-reactively and longitudinally at 3, 10, and 30 days after clipping. Three days after clipping, there were no differences in blood pressure or kidney size; however, 10 and 30 days postoperation, the clipped kidney shrank in the 2K1C model. The nonclipped 2K1C and the clipped lK1C and unilateral nephrectomy kidneys increased in weight (P < .05. At day 3 the IGF-I levels were lower (557 +/- 54, 335 +/- 61 ng/g in control and clipped 2K1C, P < .05, v 1,074 +/- 186, 1,109 +/- 54, and 1,154 +/- 200 ng/g kidney, nonclipped 2K1C, 1K1C, and NPX, respectively). At 30 days the IGF-I levels were 300 +/- 24 ng/g in control (P < .05) v clipped 2K1C, 160 +/- 19, 218 +/- 20 ng/g in nonclipped 2K1C and 406 +/- 33 and 470 +/- 34 ng/g in 1K1C and NPX, respectively (P < .05) v control and clipped 2K1C. Kidney mRNA was increased in the clipped 2K1C. In conclusion, the kidney that had higher IGF-I levels early in nonclipped 2K1C, 1K1C, and nephrectomy hypertrophied, and the kidney (clipped 2K1C) that failed to increase IGF-I atrophied. IGF-I levels are dissociated from the local mRNA message.


Asunto(s)
Hipertensión Renal/patología , Factor I del Crecimiento Similar a la Insulina/genética , Isquemia/patología , Riñón/patología , Animales , Atrofia , Enfermedad Crónica , Hipertensión Renal/fisiopatología , Hipertrofia , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/análisis , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/análisis , Isquemia/fisiopatología , Riñón/química , Riñón/cirugía , Masculino , Nefrectomía , ARN Mensajero/análisis , Ratas , Ratas Sprague-Dawley , Receptor IGF Tipo 1/genética , Circulación Renal , Ribonucleasas
13.
J Hum Hypertens ; 10(5): 287-92, 1996 May.
Artículo en Inglés | MEDLINE | ID: mdl-8817401

RESUMEN

We have shown previously that blood pressure (BP) reduction after the siesta is similar to that after night sleep. As cardiovascular events cluster around morning waking hours, when there is a sharp rise of BP and heart rate (HR), the double-product of which is a major determinant of cardiac oxygen consumption, we also investigated changes after the siesta. Twenty-four-hour ambulatory BP monitorings of 156 consecutive patients referred for evaluation of hypertension who reported the siesta (afternoon nap) were analysed. The mean daytime awake BP and HR were 145 +/- 18/80 +/- 10 mm Hg and 71 +/- 11 beats per minute (bpm). During night sleep and the siesta BP decreased significantly (P < 0.00001) to 126 +/- 20/67 +/- 10 and 125 +/- 17/65 +/- 10 mm Hg, respectively. HR decreased during the siesta (69 +/- 11 bpm; P < 0.00001) but even more so (P < 0.00001) during the night (62 +/- 8 bpm; P < 0.00001). When normotensive subjects (n = 38), untreated (n = 33) and treated hypertensives (n = 85) were evaluated separately, they all had similar trends. However, when percentage rise over the sleeping baseline was considered, there were no significant differences in the rise of BP after the siesta and night sleep. The rise in HR for the normotensives and treated hypertensives was 16% and 8%, respectively, higher in the morning than after the siesta (P < 0.0004 and P < 0.001, respectively). The double-product increased significantly more in the morning than after the siesta (both P < 0.0001) in the normotensives (by 20%) and treated hypertensives (by 10%). In untreated hypertensives the rise in HR and double-product was no different between the time periods. In conclusion, there is a higher rise of HR and double-product in the morning. The relatively lower rise after the siesta may indicate a lesser increase in cardiac oxygen consumption and, therefore, lesser potential for acute ischemia.


Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial , Presión Sanguínea , Ritmo Circadiano , Sueño , Adulto , Anciano , Frecuencia Cardíaca , Humanos , Hipertensión/fisiopatología , Persona de Mediana Edad , Estudios Prospectivos , Valores de Referencia
14.
J Hum Hypertens ; 16(6): 435-8, 2002 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12037701

RESUMEN

Non-dipping, ie failure to lower blood pressure during sleep, has been found to be more prevalent in diabetic than in non-diabetic subjects. However, the reasons remain to be clarified. Diabetic patients may wake up more frequently during the night (for instance, due to nocturia). This may result in inclusion of awake blood pressure measurements in the night-time average and thus erroneously raise this average, causing misclassification of patients as non-dippers. However, non-dipping in diabetes may be due to blunted effect of sleep itself on blood pressure secondary to autonomic neuropathy. We undertook this study in order to further clarify this question. We studied 23 diabetic patients, and 23 matched controls who underwent 24-h ambulatory blood pressure monitoring, and reported taking an afternoon nap. Afternoon nap, by virtue of its short duration, is devoid of interruptions, and thus can be used as a model for tiled, non-interrupted sleep. We found that, both in diabetic patients and controls, blood pressure declined during the afternoon nap in a similar magnitude to the night-time decline. However, this decline was significantly blunted in the diabetic patients (13.9 +/- 2.2% decline in diastolic blood pressure during naptime in the diabetic patients, as compared with 24 +/- 2.3% decline in diastolic blood pressure during the siesta in the control group, P < 0.02). The blunted decline of blood pressure during the nap in diabetic patients demonstrates that non-dipping is due to the blunted effect of sleep itself. This can be another facet of autonomic dysfunction seen in diabetes mellitus.


Asunto(s)
Diabetes Mellitus Tipo 1/fisiopatología , Sueño/fisiología , Presión Sanguínea , Monitoreo Ambulatorio de la Presión Arterial , Ritmo Circadiano , Nefropatías Diabéticas/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad
15.
Placenta ; 30(10): 898-906, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19709742

RESUMEN

Nitric oxide synthase (NOS) plays an important role in hypertensive disorders of pregnancy. In the context of the known association between hyperinsulinemia and hypertension, we studied the expression of the 3 isoforms of NOS (neuronal-nNOS, inducible-iNOS, and endothelial-eNOS) in the placenta and implantation site of our insulin-induced intrauterine growth restriction (IUGR) rat model in which the normal gestational blood pressure decline is abrogated. The fetuses of hyperinsulinemic dams were significantly smaller than those of normal pregnant dams (male fetal weight=4.8+/-0.5 g vs. 5.4+/-0.4 g, hyperinsulinemic vs. control, respectively; female fetal weight=4.5+/-0.5 g vs. 5.1+/-0.4 g, hyperinsulinemic vs control, respectively, p<0.0001). Their placentas weighed less than those of normal pregnant dams (0.44+/-0.08 g in hyperinsulinemic dams vs. 0.50+/-0.09 g, p<0.0001) and their implantation site, designated the mesometrial triangle, was also smaller. Endovascular trophoblasts were found more often and in greater depth in normal pregnant dams. Possibly as a compensatory mechanism, the endovascular trophoblasts formed cell groups rather than a monolayer and occupied a larger portion of the arterial perimeter in arteries of hyperinsulinemic dams. iNOS expression increased by 80% (p<0.0001) and 180% (p=0.045) in placenta and mesometrial triangle of hyperinsulinemic dams, respectively. The expression of eNOS was reduced by 17% (p=0.048) in the placenta and did not change significantly in the mesometrial triangle (p>0.05). nNOS expression was decreased by 37% (p=0.03) in the placenta and increased by 53% (p=0.035) in the mesometrial triangle of hyperinsulinemic dams. Immunohistochemistry revealed prominent expression of iNOS in the placental junctional zone and in interstitial and endovascular trophoblasts in the mesometrial triangle. Assuming a role in trophoblastic invasion, the increased expression of iNOS in hyperinsulinemic dams explains the "compensatory" pattern of trophoblastic invasion. Expression of eNOS was prominent in endothelial cells and weak in endovascular trophoblasts. In our model of gestational hyperinsulinemia-induced IUGR, we found not only differing expression of the 3 NOS isoforms in the cellular elements of the placenta and mesometrial triangle, but also divergent modes of altered NOS isoform expression. These findings suggest, in accordance with other publications, that each isoform may have a distinct function in the placenta and placental bed. The differing expression of the 3 NOS isoforms in the placenta and in the mesometrial triangle in rat IUGR seems to result from the hyperinsulinemia and the resulting IUGR phenotype.


Asunto(s)
Implantación del Embrión , Retardo del Crecimiento Fetal/metabolismo , Hiperinsulinismo/complicaciones , Óxido Nítrico Sintasa/metabolismo , Placenta/patología , Complicaciones del Embarazo/metabolismo , Animales , Presión Sanguínea , Ciclo Celular , Proliferación Celular , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Femenino , Retardo del Crecimiento Fetal/etiología , Retardo del Crecimiento Fetal/patología , Peso Fetal , Hiperinsulinismo/inducido químicamente , Hiperinsulinismo/metabolismo , Hiperinsulinismo/patología , Insulina/administración & dosificación , Insulina/farmacología , Miocitos del Músculo Liso/metabolismo , Óxido Nítrico Sintasa de Tipo I/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Tamaño de los Órganos , Placenta/metabolismo , Embarazo , Complicaciones del Embarazo/inducido químicamente , Complicaciones del Embarazo/patología , Ratas , Ratas Wistar , Trofoblastos/metabolismo , Trofoblastos/patología
16.
J Cardiovasc Pharmacol ; 9 Suppl 1: S76-9, 1987.
Artículo en Inglés | MEDLINE | ID: mdl-2441190

RESUMEN

The elimination of an acute oral saline load is markedly blunted in adult Sabra hypertension-prone (SBH) rats compared with hypertension-resistant Sabra normotensive (SBN) rats. Within 2 h, urinary output and the excretion of sodium and potassium are significantly reduced, while urine osmolality is markedly elevated in SBH rats. The long-term administration of nifedipine, 20-30 mg/kg body weight enhanced the diuretic and natriuretic response to saline loading in members of both strains. The effect was significantly more pronounced in SBH, especially in adult animals where the diuretic and natriuretic response averaged 150 and 130% of control, while in SBN the enhanced response was 50 and 20%, respectively. As a result of the disparate effect of nifedipine in the two strains, the blunted response of SBH was abolished. The mechanism of the preferential response to nifedipine of SBH rats remains to be determined.


Asunto(s)
Hipertensión Renal/fisiopatología , Riñón/efectos de los fármacos , Nifedipino/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Diuréticos/farmacología , Femenino , Natriuresis/efectos de los fármacos , Ratas , Ratas Endogámicas , Cloruro de Sodio/administración & dosificación
17.
Clin Exp Pharmacol Physiol Suppl ; 22(1): S28-9, 1995 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9072391

RESUMEN

1. An association between hyperinsulinaemia, insulin resistance and hypertension was previously described in spontaneously hypertensive rats (SHR). We therefore tested whether chronic exogenous hyperinsulinaemia, which did not affect blood pressure of normotensive rats, may aggravate hypertension in young SHR. 2. Insulin was administered for 4 weeks by a graded increase of a sustained release insulin implant, without carbohydrate supplementation. 3. Initial bodyweight of seven SHR and five sham-implanted control SHR, aged 6-8 weeks, was not different between the groups or by week 4. 4. Glucose levels decreased in the treated rats [2-way ANOVA F(1:10) = 18.7. P < 0.005] and were 7.3 +/- 0.1 mmol/L in the controls and 4.4 +/- 0.7 mmol/L in the treated SHR, respectively. Insulin levels were comparable at baseline and increased to 1002 +/- 978 pmol/L in treated rats at week 4 while remaining 270 +/- 78 pmol/L in the controls [F(1:10) = 6.1, P < 0.05]. The systolic blood pressure (tail-cuff) was significantly increased in insulin treated SHR in weeks 1-3[F(1:10) = 5.1, P < 0.05] though it was comparable at baseline and week 4. 5. In the presence of a hypertensive predisposition, chronic exogenous hyperinsulinaemia accelerates the time course of the development of hypertension without affecting its severity.


Asunto(s)
Hiperinsulinismo/fisiopatología , Hipertensión/inducido químicamente , Hipertensión/fisiopatología , Animales , Glucemia/metabolismo , Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Creatinina/sangre , Hipertensión/genética , Insulina/sangre , Sistemas de Infusión de Insulina , Ratas , Ratas Endogámicas SHR , Factores de Tiempo
18.
Clin Exp Pharmacol Physiol Suppl ; 22(1): S32-3, 1995 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9072410

RESUMEN

1. We tested the effects of chronic hyperinsulinaemia on renal function. Hyperinsulinaemia, in the range of 1.5-4 times the control levels, was achieved using a sustained-release insulin implant. Sham-treated rats served as controls. 2. Experiment 1. Acute saline loading: seven sham and seven hyperinsulinaemic rats received an acute saline load (4 mL/100 g). Two h post-load urea and creatinine excretion rats were (mu mol/min) 15 +/- 5 and 9 +/- 4, and 0.17 +/- 0.05 and 0.10 +/- 0.04, respectively; P < 0.05 for both. 3. Experiment 2. Chronic saline loading: 12 sham- and 24 insulin-treated rats drank saline for 8 weeks plus 4% NaCl in the food for 2 more weeks. By week 10 plasma creatinine (mu mol/L) was 62 +/- 12 and 78 +/- 13, and creatinine clearance (mL/min) was 1.9 +/- 0.5 and 1.5 +/- 0.4, respectively; P < 0.05 for both. 4. Experiment 3. Regular diet: 10 sham- and 14 insulin-treated rats had, by week 8, plasma creatinine (mu mol/L) of 75 +/- 34 and 96 +/- 37 and creatinine clearance (mL/min) of 1.260 +/- 0.025 and 0.97 +/- 0.22, respectively; P < 0.02 for both. Bodyweight, resting blood pressure and urinary Na+ and K+ excretion were comparable in sham- and insulin-treated rats. 5. In three experimental settings long-term hyperinsulinaemia was associated with a subtle but significant renal dysfunction. This finding may be related to the aetiology of renal complications of hypertension and diabetes mellitus, both of which are insulin-resistant and hyperinsulinaemic states.


Asunto(s)
Hiperinsulinismo/fisiopatología , Hipoglucemiantes/toxicidad , Insulina/toxicidad , Enfermedades Renales/inducido químicamente , Animales , Glucemia/metabolismo , Presión Sanguínea/efectos de los fármacos , Creatina/sangre , Hiperinsulinismo/complicaciones , Insulina/sangre , Enfermedades Renales/fisiopatología , Pruebas de Función Renal , Ratas
19.
Clin Exp Hypertens A ; 5(4): 493-9, 1983.
Artículo en Inglés | MEDLINE | ID: mdl-6682726

RESUMEN

The erythrocyte Na+, K+ cotransport system was studied in ten pairs of identical twins. Cation fluxes were remarkably similar in each pair of twins, which supports the concept of a genetic determinant for the cotransport system. There was, however, no apparent correlation between cotransport values and the family history of hypertension.


Asunto(s)
Presión Sanguínea , Eritrocitos/metabolismo , Potasio/sangre , Sodio/sangre , Gemelos Monocigóticos , Gemelos , Adolescente , Adulto , Niño , Preescolar , Enfermedades en Gemelos , Femenino , Furosemida/farmacología , Humanos , Hipertensión/sangre , Hipertensión/genética , Masculino , Persona de Mediana Edad , Embarazo
20.
Hypertension ; 36(5): 872-7, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11082159

RESUMEN

We previously found that chronic exogenous hyperinsulinemia without sugar supplementation does not elevate blood pressure. This may be partially explained by the ability of insulin to release nitric oxide and cause vasodilatation. To test this hypothesis, we studied 4 groups of rats: 9 rats (body weight, 213+/-14 g) treated with a gradual increase of a sustained-release subcutaneous insulin pellet; 9 rats (body weight, 213+/-9 g) treated with N:(G)-nitro-L-arginine methyl ester (L-NAME) in drinking water 50 mg/L; 19 rats (body weight, 217+/-11 g) treated with the combination of L-NAME and insulin; and 9 control rats (body weight, 218+/-11 g). Blood pressure was followed weekly for 6 weeks, and then rats were studied in metabolic cages. Weight gain was not different during the 6 weeks. Renal function did not differ between the 4 groups, but 24-hour urinary nitrite/nitrate excretion was lower (P<0.02) in L-NAME-treated and higher in insulin-treated rats. Plasma insulin doubled (P<0.002) in the insulin-treated rats, but there was no hypoglycemia and, by week 6, fructosamine levels were 2.1+/-0.2, 2.1+/-0.2, 2.3+/-0.1, and 2.3+/-0.2 mmol/L in control rats and rats treated with L-NAME, insulin, and L-NAME plus insulin, respectively. Systolic blood pressure, which did not differ at baseline, at week 3 was 122+/-17, 118+/-17, and 118+/-24 mm Hg in the control, L-NAME, and insulin groups and 136+/-14 mm Hg (P<0.03) in the combination group. At week 6, systolic blood pressure was 128+/-14, 127+/-15, and 118+/-13 mm Hg in the control, L-NAME, and insulin groups, respectively, and 150+/-14 mm Hg (P<0.0005) in the combination group. In a subsequent experiment, L-arginine 2 g/L abrogated the effects of L-NAME and insulin combination. In conclusion, chronic exogenous hyperinsulinemia does not affect blood pressure but may cause hypertension when endothelial function is compromised.


Asunto(s)
Presión Sanguínea/efectos de los fármacos , Inhibidores Enzimáticos , Hiperinsulinismo/diagnóstico , Hipertensión/diagnóstico , NG-Nitroarginina Metil Éster , Animales , Enfermedad Crónica , Relación Dosis-Respuesta a Droga , Implantes de Medicamentos , Inhibidores Enzimáticos/farmacología , Hiperinsulinismo/sangre , Hiperinsulinismo/complicaciones , Hipertensión/sangre , Hipertensión/inducido químicamente , Insulina/administración & dosificación , Insulina/sangre , Insulina/farmacología , Masculino , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/metabolismo , Óxido Nítrico/fisiología , Ratas , Ratas Sprague-Dawley , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiología
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