Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In Caucasian subjects, elevated erythrocyte sodium-lithium countertransport (SLC) activity, displaying an increased affinity for external Na+ (decreased KNa), has a strong association with hypertension and has also been proposed as a potential marker for vascular disease. We have compared SLC activity and the kinetic components, KNa and maximal rate of turnover (Vmax), of the countertransporter in groups of Caucasian, Asian and Black hypertensive subjects matched for ethnicity, age and sex with healthy normotensive controls. SLC activity was the same in all ethnic groups irrespective of the presence of hypertension. Similarly, hypertension had no impact on Vmax values within each ethnic group (normotensive vs. hypertensives: Caucasian, 0.360 +/- 0.186 vs. 0.335 +/- 0.137; Asian, 0.324 +/- 0.078 vs. 0.273 +/- 0.105; black people, 0.192 +/- 0.123 vs. 0.178 +/- 0.082 mmol Li/l erythrocytes h). However, in black people compared with the other two ethnic groups, Vmax was lower for both controls and hypertensives (P < 0.05; ANOVA). Median KNa values in hypertensive subjects were consistently lower than their normotensive counterparts in all ethnic groups (P < 0.01; Kruskal-Wallis); Caucasians, (89.1 vs. 41.2 mmol Na; P = 0.01), Asians (121.1 vs. 33.1; P = 0.04) and black people (74.4 vs. 27.2 mmol Na; P = 0.02; Wilcoxon). The results show that Vmax is altered in black people independently of the presence of hypertension. This contrasts with KNa which, for each ethnic group studied, is reduced in the hypertensive compared with the normotensive state.
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PMID:Ethnic origin and hypertension-associated alterations in sodium-lithium countertransport kinetics. 852 92

We examined whether blood pressure reduction or good glycemic control equally lower albuminuria by preventing glomerular loss of heparan sulfate and progression of glomerulosclerosis in streptozotocin-induced diabetic rats. We used doxazosin, and alpha 1-adrenergic blocker, to lower systemic blood pressure, and good glycemic control was achieved by insulin treatment. Rats were killed after 20 weeks of treatment. Doxazosin significantly lowered systolic pressure in diabetic rats; however, it had no effect in normal rats. Good glycemic control also lowered systolic pressure. In diabetic rats with good glycemic control, doxazosin had an additive effect on blood pressure. Glomerular heparan sulfate synthesis was significantly lower and urinary albumin excretion higher in diabetic than in normal rats. Both doxazosin treatment and good glycemic control normalized these abnormalities in diabetic rats. Insulin normalized plasma glucose and glycosylated HbA1 concentrations in diabetic rats, as did doxazosin. Significant increases in mesangial area and glomeruloscelerosis were observed in diabetic rats. Only good glycemic control normalized these pathological changes in all diabetic rats. Two-way factorial ANOVA showed an interaction between the effects of doxazosin and insulin on systolic pressure and plasma glucose. The data show that after 20 weeks of doxazosin treatment, albuminuria was reduced by 80%; however, this treatment had no significant effect on mesangial expansion or progression to glomerulosclerosis. Conversely, good glycemic control prevented all three of the preceding sequelae.
Hypertension 1996 May
PMID:Doxazosin prevents proteinuria and glomerular loss of heparan sulfate in diabetic rats. 862 Dec 4

To investigate the effect of vascular smooth muscle contraction on mechanical vessel wall properties of proximal "elastic" arteries, we investigated the effect of the vasoconstrictor ergotamine on the distensibility of the common carotid artery in 10 migraine patients with ergotamine intake, in 10 control patients with migraine headache but no prior ergotamine intake, and in 10 healthy control subjects. The patients and control subjects were matched for age, blood pressure, and sex. In the ergotamine group, 2.2 +/- 1.4 mg ergotamine tartrate (0.25 to 6 mg) was taken within 12 hours before investigation. Differences in mean 24-hour blood pressure between the study groups were excluded by 24-hour blood pressure recording and differences in arterial wall thickness by high-resolution and differences in arterial wall thickness by high-resolution B-mode ultrasound. A multigate Doppler system was used for measurement of vessel wall movements by M-mode Doppler analysis. Blood pressure was determined by sphygmomanometry. The end-diastolic diameter of the common carotid artery was insignificantly reduced in the ergotamine group compared with the healthy control subjects and control patients (healthy control subjects, 6.6 +/- 0.4 mm; control patients, 6.7 +/- 0.5 mm; patients with ergotamine intake, 6.3 +/- 0.4 mm; P = NS). Arterial distensibility was significantly lower in the patients with ergotamine intake (17.4 +/- 4.0 10(-3)/kPa) than in the healthy control subjects (22.3 +/- 5.1 10(-3)/kPa) and control patients (22.8 +/- 3.6 10(-3)/kPa) (one-way ANOVA, P = .014). The results show that ergotamine reduces the distensibility of the common carotid artery. The data suggest that vascular smooth muscle contraction can modulate the buffering function of the arterial system independently of blood pressure changes.
Hypertension 1996 Jul
PMID:Reduced distensibility of the common carotid artery in patients treated with ergotamine. 867 50

Plasma levels of fasting and post-prandial blood sugar, serum levels of total cholesterol (TC), triglycerides (TG), HDL cholesterol (HDLc), LDL cholesterol (LDLc) and free fatty acids (FFA) were estimated in 213 diabetic patients (NIDDM) with coronary heart disease (CHD-group 4), 252 CHD patients (non-diabetic CHD-group 3), 164 non-insulin dependent diabetics (NIDDM-group 2) and 173 healthy subjects (controls-group 1) who did not have any clinical evidence of CHD, diabetes mellitus or any family history of the above diseases. Data was analysed by ANOVA along with the Duncan procedure and multiple logistic regression. Lipid profile of diabetic CHD patients was characterised by significantly higher concentration of TC, TG, LDLc, FFA, LDLc/HDLc ratio and lower concentration of HDLc. However, in a multivariate logistic regression analysis using 14 known risk factors, diastolic blood pressure (BP), body mass index (BMI), alcohol consumption and higher FFA levels seemed to be predictors of CHD in diabetics, overriding the influence of lipoprotein abnormalities. The same was true for nondiabetic patients also in whom BMI, FFA and alcohol consumption were found to be significant predictors of CHD. Thus, even though lipid abnormalities are more prominent in diabetics, the coexistence of obesity and hypertension seem to be important factors in diabetics for the development of CHD.
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PMID:Risk factors for coronary heart disease in noninsulin dependent diabetes mellitus (NIDDM). 871

We determined the dynamic and steady state responses of heart rate (HR) to orthostatic stress (standing up) in normotensive and hypertensive pregnant women. Using a continuous recording with servo-photosphygmography, HR response to change in posture from left lateral recumbent position to standing was analysed. The subjects were divided into five groups comprising: Groups I, II and III: normotensive pregnant women in each of the three trimesters of pregnancy (total n = 77); Group IV: women with gestational proteinuric hypertension (GPH) in the third trimester (n = 16); Group V: age-matched non-pregnant normotensive controls (n = 15). The HR reacted with a typical overshoot response to this orthostatic change with HR rising to a peak and then settling to a new but higher steady state. Change in steady state HR from lying to standing (delta HR), rate of rise of HR in response to standing (i.e. the acceleration slope (HRon)), and rate of fall of HR after reaching the peak (i.e. deceleration slope (HRoff)) were evaluated from standing heart rate time curves. HRon in response to standing showed a downward trend with gestation (ANOVA, P < 0.05) in normotensive gravida. The deceleration slope (HRoff) showed a distinct gestational age-related decrease from first to third trimester in normotensive women (ANOVA, P < 0.01). The most striking observation was that the slope of HRoff for the GPH group was significantly steeper than that of normotensive women of comparable gestational age (unpaired t-test P < 0.01) and approximated to that of the non-pregnant group. The difference in HR response between normotensive women and those with GPH in the third trimester suggests it may have potential as a new marker for pre-eclampsia.
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PMID:Dynamic and steady state response of heart rate to orthostatic stress in normotensive and hypertensive pregnant women. 873 55

Aortic clamp-induced hypertension has long been implicated in the cardiovascular mortality and morbidity following infrarenal aortic operations. We studied the physiologic mechanisms leading to clamp-induced hypertension. Mean arterial pressure (MAP), cardiac output, heart rate, and left ventricular pressure were measured in alpha-chloralose-anesthetized dogs. Animals received alpha, beta, both alpha and beta, or no adrenergic blockade (n = 3, 4, 12 and 7, respectively). The infrarenal aorta was clamped following ligation of the infrarenal collateral vessels (lumbar, circumflex iliac, and tail arteries). Statistical analysis used paired t tests within groups, and ANOVA and unpaired t tests between groups, with Bonferroni's correction as indicated. Following placement of the clamp, MAP increased immediately in all groups, with magnitude of the increase related to the extent of adrenergic blockade. MAP increased 5.6 +/- 0.8 mm Hg with no blockade (P = 0.0005), 6.7 +/- 0.8 mm Hg with alpha blockade (P = 0.0153), 15 +/- 3.1 mm Hg with beta blockade (P = 0.0163), and 16.7 +/- 1.3 mm Hg with combined alpha and beta blockade (P < 0.0001). The increase in MAP immediately following infrarenal aortic clamping was most pronounced with combined alpha and beta blockade. We suggest that acute intraoperative hypertension associated with infrarenal aortic clamping is caused by the attenuation of compensatory baroreceptor reflex mechanisms.
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PMID:Infrarenal aortic clamp hypertension is exacerbated by baroreceptor blockade. 881 20

This study was designed to explore the effect of race and gender on the forehead muscle tension and finger temperature response to biofeedback-assisted relaxation training in individuals with normal blood pressure. Forty-five subjects-18 Black and 27 White, 25 males and 20 females-participated in eight sessions of autogenic relaxation training and thermal biofeedback. Multivariate analysis of variance of the variables measured at baseline (systolic BP diastolic BP sodium excretion, anxiety) was significant for gender Univariate analysis showed males different from females in DBP Na(+) excretion, and trait anxiety. Pretest values of muscle tension were similar by gender, but pretest temperatures were lower in males than females. Repeated measures ANOVA for muscle tension showed a significant effect of period. For temperature a significant effect of period, gender and gender x period was observed. Males increased temperature more than females. There was no effect of history of hypertension on the relaxation response. Multiple regression performed on change in muscle tension and change in temperature showed that pretest muscle tension predicted change in muscle tension. Four variables contributed to the variance in change in temperature: pretest temperature, sodium excretion, and state and trait anxiety.
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PMID:Racial and gender effects on the relaxation response: implications for the development of hypertension. 883 16

Abnormalities of the arterial pulse waveform reflect changes in cardiovascular structure and function. These abnormalities may occur early in the course of essential hypertension, even before the onset of blood pressure elevation. Previous studies of cardiovascular structure and function have relied on invasive intra-arterial cannulation to obtain the arterial pulse wave. We evaluated arterial structure and function using a noninvasive cuff sphygmomanometer in hypertensive (n = 15) and normotensive (n = 36) subjects stratified by genetic risk (family history) for hypertension. Using a simple physical model in which the aorta was assumed to be a T tube and the brachial artery a straight tube, we determined vascular compliance and peripheral resistance by analyzing the brachial artery pulsation signal from a cuff sphygmomanometer. Essential hypertensive subjects tended to have higher peripheral resistance (P = .06) and significantly lower vascular compliance (P = .001) than normotensive subjects. Vascular compliance correlated with simultaneously determined pulse pressure in both groups (n = 51, r = .74, P < .0001). Higher peripheral resistance (P = .07) and lower vascular compliance (P = .04) were already found in still-normotensive offspring of hypertensive parents (ie, normotensive subjects with a positive family history of hypertension) than in normotensive subjects with a negative family history of hypertension. Multivariate analysis demonstrated that both genetic risk for hypertension (P = .030) and blood pressure status (P = .041), although not age (P = .207), were significant predictors of vascular compliance (multiple R = .47, P = .011). However, by two-way ANOVA, genetic risk for hypertension was an even more significant determinant (F = 7.84, P = .007) of compliance than blood pressure status (F = 2.69, P = .089). Antihypertensive therapy with angiotensin-converting enzyme inhibitors (10 days, n = 10) improved vascular compliance (P = .02) and reduced resistance (P = .003) significantly; treatment with calcium channel antagonists (4 weeks, n = 8) tended to improve vascular compliance (P = .07) and significantly reduced peripheral resistance (P = .006). We conclude that arterial vascular compliance abnormalities detected by a noninvasive cuff sphygmomanometer reflect treatment-reversible changes in vascular structure and function. Early changes in vascular compliance in still-normotensive individuals at genetic risk for hypertension may be a heritable pathogenetic feature of this disorder.
Hypertension 1996 Oct
PMID:Arterial compliance by cuff sphygmomanometer. Application to hypertension and early changes in subjects at genetic risk. 884 84

While essential hypertension may be characterized by insulin resistance, it is unclear which defect is primary. We therefore compared normotensive Sprague-Dawley male rats who drank N-nitro-L-arginine methyl ester (L-NAME, 1 mg/mL in distilled water), with control rats who drank distilled water. Blood pressure was measured noninvasively, weight was controlled by dietary restriction, and glucose tolerance was assessed via oral glucose tolerance tests (OGTT). Blood pressure rose by the second day of L-NAME treatment, and remained elevated throughout the study, in contrast to the rats drinking water (P < .001). Weight rose similarly in both groups. OGTT were performed after 2 weeks of L-NAME. Serum glucose and insulin responses, assessed by two-way ANOVA, were similar in the two groups (P = NS). In summary, L-NAME administration resulted in hypertension, but not a deterioration in glucose tolerance in diet-controlled Sprague-Dawley rats. We conclude that the insulin resistance of some hypertensive states is not the result of hypertension per se, or increased vasoconstriction, such as might result from inhibition of endogenous nitric oxide synthesis, but rather indicates a fundamental metabolic disorder.
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PMID:Oral administration of the nitric oxide biosynthesis inhibitor, N-nitro-L-arginine methyl ester (L-NAME), causes hypertension, but not glucose intolerance or insulin resistance, in rats. 884 69

Several complex clinical and statistical issues are involved in the development of a combination drug product. The medical rationale for the combination, the intended clinical use, drug-drug interactions, and dose response are just a few of the considerations. The factorial design is a useful experimental model for evaluating combination therapies. This paper outlines some of the considerations involved in the use of this design in the study of combination drugs. Questions related to design and methods of analysis are discussed in general and through use of an example. Such a design was applied to study the combination of a vasodilator with a diuretic in the treatment of hypertension. The sample size derivation, the evaluation of "interaction," the use of ANOVA versus regression techniques, and methods of data display are reviewed. It is recognized that although these are complex issues, substantially more information per patient can be obtained than with standard parallel-design approaches. The design could be an especially powerful tool early in the development of a drug.
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PMID:An approach to the assessment of therapeutic drug interactions with fixed combination drug products. 885 28


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