摘要:

Several experimental models involving the development of cardiac hypertrophy in adult rats are characterized by the reexpression of the fetal isoform of myosin heavy chain (V3). To determine whether a similar adult-to-fetal shift in the expression of the thin-filament proteins occurs during cardiac hypertrophy, we have examined the expression of the isofonns of myosin, tropomyosin, and troponin T in the left ventricle of young spontaneously hypertensive rats (SHR) with and without treatment using enalapril, an angiotensin converting enzyme inhibitor. Phosphorylation of tropomyosin, which is predominant in the fetal state, was also analyzed. Twelve-week-old SHR were treated with enalapril for 2,5,8, and 9 weeks followed by withdrawal of treatment for 9 weeks. Control SHR, without drug treatment, were weight- and age-matched. After 9 weeks of enalapril treatment, mean arterial blood pressure was reduced (from 166±11 to 89±5 mm Hg), and left ventricular weight/body weight ratio was regressed (from 2.53±0.14 to 1.96±0.05 g/kg) to normotensive levels. During the 9-week treatment period, the percent V3decreased in SHR substantially from 35±3% to 13±1%. There was a significant correlation between the left ventricular hypertrophy and the percent V3myosin expression in the SHR during regression (r= 0.697,p< 0.001). However, only the adult isofonns of tropomyosin and troponin T were detected in the SHR with or without enalapril treatment, and the level of tropomyosin phosphorylation remained constant irrespective of the degree of left ventricular hypertrophy. These results suggest that the adult-to-fetal switch in the expression program of myosin isofonns that accompanies the development of left ventricle hypertrophy is not adopted by the thin-filament proteins, tropomyosin and troponin T.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Human active renin can be separated into at least five forms by isoelectric focusing. The present study assessed the preferential renal secretion and hepatic degradation of renin forms in humans. The renin form profile of secreted renal renin was determined before transplant in an ex vivo kidney donor perfusion system and compared with the peripheral plasma multiple renin form profile of normal subjects. The effect of hepatic degradation on renin forms was assessed in hepatic vein plasma in comparison with infrarenal vena cava plasma in hypertensive patients during renal vein renin studies. The results revealed a significantly greater proportion of the more basic forms in the perfusate of donor kidneys compared with normal plasma. In hypertensive patients the proportion of the more basic renin forms in the hepatic vein was significantly decreased in comparison with the infrarenal vena cava. Thus, the human kidney may preferentially secrete the more basic renin forms. In contrast, the liver preferentially degrades the more basic forms, giving these forms a shorter plasma half-life. The preferential secretion and clearance of the more basic forms of renin may contribute to short-term control of human renin-angiotensin system activity.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The relation between endothelin and acetylchollne (ACh) was examined and compared in aortas from Wistar-Kyoto (WKY) rats and from stroke-prone spontaneously hypertensive rats (SHRSP). The relaxation produced by ACh in an endothelin-induced contraction was less in aortas from WKY rats than in those from SHRSP. In aortas from WKY rats but not in those from SHRSP, the contraction produced by endothelin was augmented when the intact aortic rings were treated with methylene blue (10−5M). This augmentation was also found in preparations of the WKY rat aortic rings in which the endothelium had been removed. The augmentation was not present in SHRSP aortic rings that had been similarly denuded. Treatment with indomethacin (5 × 10−6M) had no effect on endothelin-induced contraction in either WKY rat or SHRSP aortic rings. Our findings indicate that endothelin and ACh have in common the ability to release endothelium-derived relaxing factor (EDRF) in WKY rat aortic rings. The reduced endothelium-dependent relaxation in response to ACh in the WKY rat probably reflects the fact that endothelin had already released the EDRF in rings from this strain of rats. The release of EDRF by endothelin is less in SHRSP than it is in WKY rats. Because of this failure of endothelin to release EDRF in SHRSP, endothelin may contribute to the increase in total peripheral resistance in this form of hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Forty-seven male patients with mild essential hypertension were randomly allocated to three subgroups. After a run-in period of 4 weeks, the first subgroup (n= 16) received propranolol (80 mg/day) for 36 weeks followed by a placebo period of 4 weeks. The second subgroup (n= 15), after a run-in period of 4 weeks, was given a supplement of encapsulated fish oil (9 g/day) for 36 weeks with a subsequent period of 4 weeks in which fish oil placebo was given. The third subgroup (n= 16), after a run-in period of 4 weeks, was given propranolol (80 mg/day) for 12 weeks, propranolol (80 mg/day) plus fish oil capsules (9 g/day equivalent to 1.8 g/day of eicosapentaenoic acid and 1.1 g/day of docosahexaenoic acid) for 12 weeks, propranolol plus fish oil placebo (same doses for 12 weeks) with a subsequent period of 4 weeks when propranolol placebo was administered. The results indicate a blood pressure-lowering effect of fish oil, which was comparable with that of propranolol. The simultaneous intake of fish oil plus propranolol was more effective than propranolol or fish oil alone. Propranolol treatment resulted in a decrease of plasma norepinephrine, plasma renin activity, and thromboxane B2formation. After fish oil supplementation, plasma norepinephrine and thromboxane B2formation were likewise reduced, whereas plasma renin activity appeared increased. The decrease of serum triglycerides, total and low density lipoprotein cholesterol as well as the rise of high density lipoprotein cholesterol are concomitant beneficial effects, which justify the consideration of fish oil alone or in combination with antihypertensive drugs for the treatment of mild hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Does the average daily blood pressure correlate with hypertensive cerebrovascular disease better than the casual pressure, as has been reported in other target organ involvement? We investigated the associations of two abnormal findings on brain magnetic resonance imaging suggestive of a vascular etiology, low intense foci (lacunae), and periventricular hyperintense lesions on T1- and T2-weighted images, with both office and average daily blood pressure values in a population of 73 healthy normotensive and hypertensive elderly individuals (70±6 years old). Lacunae were detected in 34 subjects (47%); the number per subject ranged from 0 to 19 and was significantly correlated with advancing age. Furthermore, these changes were supposedly related to the average of noninvasive ambulatory (24-hour and during awake and asleep periods) pressure recordings but not to office pressures. The grade of periventricular hyperintensity was also significantly associated with advancing age and the average of ambulatory systolic pressure recordings, particularly during sleep, but not with office blood pressure. In comparisons of normotensive, “office hypertensive,” and hypertensive subgroups, abnormalities on magnetic resonance imaging were appropriate to the level of the 24-hour blood pressure measurements but not to that of clinic pressure. In hypertensive patients, the presence of electrocardiographic evidence of left ventricular hypertrophy was also associated with greater abnormalities on magnetic resonance imaging. We conclude that ambulatory blood pressure monitoring is superior to casual pressure measurements in predicting latent cerebrovascular disease, which is unexpectedly common in apparently healthy elderly subjects.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

To study whether the proportion of excess cardiovascular events attributable to various levels of systolic blood pressure varies with age, we calculated the population-attributable risk of all-cause mortality, fatal and nonfatal cardiovascular events (stroke, coronary heart disease, angina, congestive heart failure, and peripheral vascular disease), and stroke incidence due to systolic blood pressure in men and women 45 years of age or older in the United States during 1980. Our estimates are based on US census counts, blood pressure prevalence distributions from the second National Health and Nutrition Examination Survey, and the annual risk of cardiovascular complications during 18 years of follow-up in the Framingham cohort We then determined the impact of age on the relative efficacy of mass treatment and case-finding strategies in preventing systolic blood pressure-related events. At 45–54 years of age, only 30–40% of systolic blood pressure-related excess events occur in hypertensive individuals (systolic blood pressure ≥160 mm Hg). With increasing age, however, the percentage of systolic blood pressure-related events that occur in hypertensive individuals rose substantially, in the oldest age group (≥75 years), 65–70% of fatal and nonfatal cardiovascular disease events occur in hypertensive persons. The pattern is similar for men and women. The potential impact of a mass treatment strategy designed to shift the distribution of blood pressure downward by a small amount is greater in younger than in older groups, whereas an opposite trend is seen for a high-risk, hypertensive case-finding and treatment approach. In every age, a combined mass and high-risk treatment strategy is superior to either strategy alone. Our analysis suggests that the age of the target population should be considered when designing interventions to prevent blood pressure-related cardiovascular disease

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Insulin resistance, independent of obesity or non-insulin-dependent diabetes mellitus, has been demonstrated to be associated with high blood pressure. To determine if insulin resistance could be an antecedent to hypertension in a high-risk population, we studied normotensive (112±12/70±10 mm Hg) and borderline hypertensive (135±8/85±5 mm Hg) lean young black men (22–26 years old) with the euglycemic hyperinsulinemic clamp technique. All subjects had clinically normal oral glucose tolerance. Body mass index and percent adipose mass were the same in both groups. Fasting plasma insulin concentration was significantly higher in the borderline hypertensive group (p< 0.01). Insulin-directed exogenous glucose metabolism at the same degree of steady-state hyperinsulinemia was significantly lower in the borderline hypertensive group (5.98±2.22 versus 8.22±1.96 mg/kg/min;p< 0.01). For the total population, a significant inverse correlation existed between the glucose infusion rate and systolic blood pressure (p< 0.01). These data indicate that there is a relation between insulin-mediated glucose uptake and blood pressure. Furthermore, in this high-risk population insulin resistance may precede the onset of established essential hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

A prospective study was conducted to compare the frequency of renin gene polymorphisms in normotensive and hypertensive subjects. Hypertensive (n= 102, blood pressure 168±17/103±9 mm Hg) and normotensive (n= 120, blood pressure 122±10/75±9 mm Hg) subjects were white, had similar age and sex distributions (hypertensive group, 45±10 years old and 52% female; normotensive group, 44±9 years old and 55% female) and similar body mass index (hypertensive group, 23.2±2.6; normotensive group, 22.5±2.4 kg/m2p= 0.048). The familial susceptibility to hypertension was defined as at least one parent and one sibling who were hypertensive before age 65; subjects in the normotensive group had no familial history of hypertension. Renin gene polymorphisms located throughout the renin gene were identified by using three restriction enzymes (Taq I, Hinfl, HindIII). For each polymorphic restriction site, allele frequencies were similar in the hypertensive and the normotensive groups. In the absence of parental genotypes, the haplotype frequencies combining the three restriction fragment length polymorphisms were estimated by using maximum likelihood techniques and were similar in both groups (hypertensive group, 0.429, 0.277, and 0.177; normotensive group, 0.453, 0.245, and 0.195 for the three most common haplotypes). A rare haplotype detected byTaq I/HindIII. was apparently more frequent in the hypertensive than in the normotensive group (hypertensive group,tH0.086,th0.022; normotensive group,tH0.038,th0.050), but the difference was not statistically significant In conclusion, no association between renin gene polymorphisms and essential hypertension was demonstrated in the present study.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The spontaneously hypertensive rat is the most widely studied animal model of essential hypertension, yet the genetics of transmission of high blood pressure in this strain have not been clearly defined. It has been proposed that in the spontaneously hypertensive rat, blood pressure follows a simple additive mode of inheritance and that the hypertension is primarily determined by a single major locus. To investigate the genetics of transmission of increased blood pressure in the spontaneously hypertensive rat, we performed a biometric genetic analysis of multiple, direct measurements of arterial pressure in unanesthetized, unrestrained rats derived by crossing spontaneously hypertensive rats with two different inbred normotensive strains, the Charles River Wistar-Kyoto rat and the Lewis rat In both crosses, approximately 60% of the variation in blood pressure could be assigned to genotypic variation. The data fit an additive-dominance model of inheritance in which alleles decreasing blood pressure were partially dominant Thus, in offspring derived from crosses between spontaneously hypertensive rats and Wistar-Kyoto rats or spontaneously hypertensive rats and Lewis rats that are raised under ordinary laboratory conditions, increased blood pressure is not determined by simple additive effects of alleles at a single major locus. The current findings are consistent with the possibility that in the spontaneously hypertensive rat, hypertension may arise from mutations in alleles that ordinarily act in a dominant fashion to suppress blood pressure.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

In this short paper, I have tried to explain the elation that we felt when we first realized that the kidney-fluid mechanism for controlling the arterial pressure has an infinite feedback gain property. Because of this, all the other pressure control mechanisms, none of which has ever been shown to have a similar infinite gain property, must themselves alter the kidney-fluid mechanism if they are to succeed in causing long-term changes in the arterial pressure. We have not been able to refute this principle despite many experiments over the last 2 decades. For this reason, our first understanding of the infinite gain property of the kidney-fluid mechanism was like a light at the end of the tunnel. I hope that I can explain to the reader the excitement of those few seconds when we first recognized the principle in 1966.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID