摘要:

To assess the effect of hypertension on diet-induced coronary artery plaques after a return to a nonatherogenic diet, 10 cynomolgus monkeys were fed an induction regimen containing 2% cholesterol and 25% peanut oil for 6 months and then were subjected to midthoracic aortic coarctation to induce hypertension. The animals were then fed a nonatherogenic "prudent" ration for 6 additional months (hypertension-regression group). Twelve additional monkeys were fed the atherogenic diet for 6 months; six were killed (lesion-induction control group) and six were changed to the prudent diet for 6 additional months without coarctation (nonnotension-regression control group). At the end of the induction period, cholesterol levels averaged 744±178 mg/dl for the 22 animals and were similar for the three groups throughout the induction period. For the animals restored to the nonatherogenic diet (hypertension-regression and nonnotension-regression groups), serum cholesterol levels fell to 486±252 mg/dl at 1 month, to 341 ±162 mg/dl at 2 months, and to 234±78 mg/dl at 6 months. There was no significant difference between the hypertensive and normotensive animals. Six months after coarctation, blood pressure proximal to the coarctations for the hypertension-regression group ranged from 100/60 to 220/145 mm Hg with a mean of 166/103±36/28 mm Hg. Cross-sectional area of coronary plaques was somewhat lower for the nonnotension-regression control group compared with the lesion-induction control group, but the difference was not significant Plaque area was, however, markedly greater in the hypertensionregression group than in either the lesion-induction or the normotension-regression groups (p<0.05 for each) despite progressive reduction in hyperiipidemia. Furthermore, individual mean lesion area for the hypertension-regression group correlated positively, linearly, and significantly with individual levels of mean, systolic, or diastolic pressure (p<0.001 for each). Regardless of blood pressure level or lesion area, lumen area remained normal because artery size increased with the increase in plaque area (r=0.73,p<0.02). Although hypertension sustained lesion progression under these experimental conditions, our findings do not indicate that cholesterol lowering in the presence of hypertension is necessarily without effect on coronary atherosclerosis.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Hypertension is associated with an impairment of endothelium-dependent relaxation. The angiotensin converting enzyme inhibitors captopril and cilazapril can prevent this endothelial dysfunction. We recently observed that long-term treatment with cilazapril could also prevent subendothelial infiltration by mononuclear cells in spontaneously hypertensive rats. This prompted us to examine whether, in spontaneously hypertensive rats, endothelial dysfunction and subendothelial infiltration by mononuclear cells are associated. These cells were characterized as monocyte macrophages. Infiltration by monocyte macrophages was quantified by morphometry. Endothelial function was estimated by calculating serotonin ratio (maximal contraction to serotonin on isolated arterial rings with endothelium over maximal contraction on paired rings without endothelium). The regional distribution of endothelial dysfunction and subendothelial monocyte macrophages was similar. Both were maximal in the carotid artery, less in the aorta, and nonexistent in the renal artery. A 2-week treatment with cilazapril decreased both endothelial dysfunction (serotonin ratio decreased by 32%) and the number of subendothelial monocyte macrophages in the aorta, which decreased by 38%. We conclude that in spontaneously hypertensive rats, endothelial dysfunction and subendothelial monocyte macrophage infiltration are associated and that cilazapril can decrease both. The observation that angiotensin converting enzyme inhibitors affect subendothelial accumulation of monocyte macrophages may lead to a better understanding of the mechanism of action of this class of drugs.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We have previously reported that antioxidant drug intervention protects against magnesium deficiency-induced myocardial lesions. In the present study, Golden Syrian male hamsters were fed either a magnesium-deficient diet or a magnesium-supplemented diet Animals from each group received sulfhydryl-containing angiotensin converting enzyme inhibitors: captopril, epi-captopril (a stereoisomer of captopril), and zofenopril* (arginine blend of zofenopril containing a free SH group); another group of animals received the non-sulfhydryl-containing angiotensin converting enzyme inhibitor enalaprilat The animals were killed after 14 days, and their hearts were isolated for morphological and morphometric analyses. Hematoxylin and eosin-stained sections were examined by a computer image analysis system for a morphometric determination of the severity of myocardial injury. Captopril reduced both the density of lesions, from 0.32 to 0.08 lesions/(mm2) (p<0.01), and the area fraction of lesions, from 7.42xlO"4 to 2.03 xlO"4 lesion area/(mm2) (p<0.01), as well as the degree of inflammatory infiltration around the blood vessels. Epi-captopril and zofenopril* were virtually equipotent to captopril, but enalaprilat afforded only slight (nonsignificant) protection. These results indicate that a significant component of the protective effect of captopril in this model was attributable to its sulfhydryl moiety, rather than solely due to the inhibition of the angiotensin converting enzyme. These data further support our previous findings of possible free radical participation in cardiomyopathy due to magnesium deficiency.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

To evaluate the effects of hypertension on cardiac hypertrophy, on myocardial structure, and on ventricular arrhythmias, 27 3-month-old spontaneously hypertensive rats were treated with enalapril (10 ing/kg) daily for 11 months and compared with 26 untreated control rats. Systolic arterial pressure was significantly decreased in treated rats, and at the end of the experiment, it was 199±3 mm Hg (treated) versus 237±3 mm Hg (controls) (p<0.001). At this time, spontaneous arrhythmias and induced arrhythmias either by programmed electrical stimulation (train of stimuli +1 or 2 extrastimuli) or by trains of eight stimuli at decreasing coupling intervals were observed in isolated heart preparations. Comparing enalapril-treated and control rats, spontaneous arrhythmias (9 of 27 versus 20 of 26, respectively, p<0.01), programmed stimulation-induced arrhythmias (3 of 26 versus 12 of 23, respectively; p<0.01), and trains of stimuli-induced arrhythmias (4 of 26 versus 14 of 19, respectively, p< 0.001) were less frequent in the enalapril group. Left ventricular weight was decreased in treated rats by 18% (p<0.001). Enalapril administration diminished the fraction of myocardium occupied by foci of replacement fibrosis normally occurring in control rats by 59% (/?< 0.001). Finally, a significant correlation was found between left ventricular weight, the extent of myocardial fibrosis, and the occurrence of ventricular fibrillation. It was concluded that chronic treatment with enalapril, which resulted in attenuation of systemic arterial pressure by limiting cardiac hypertrophy and myocardial fibrosis, decreases the propensity of the heart of hypertensive rats to arrhythmogenesis.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

To test the hypothesis that prostanoids contribute to angiotensin H-induced vascular contraction, we compared the effect of angiotensin II on isometric tension development by rings of descending thoracic aorta bathed in Krebs' bicarbonate buffer with and without indomethacin (10 fiM) to inhibit cyclooxygenase, CGS13080 (10 fiM) to inhibit thromboxane A2 synthesis, or SQ29548 (1 fiM) to block thromboxane A2/prostaglandin endoperoxide receptors. The comparisons were made in rings of aorta taken from nonnotensive rats and from rats with aortic coarctation-induced hypertension at 12 days and 90-113 days after coarctation. These rings released thromboxane B2, which was found to be endothelium dependent, increased in hypertensive rats, and stimulated by angiotensin II (10~6 M) in normotensive rats and in hypertensive rats at 12 days after coarctation. The angiotensin II (10~6 to 10~5M)-induced contraction of aortic rings was increased by about 30% at 12 days after coarctation and decreased at 90-113 days after coarctation. Removal of the endothelium increased the contractile effect of angiotensin II (10"' M) in aortic rings of normotensive rats and hypertensive rats at 90-113 days after coarctation but decreased the effect in aortic rings of hypertensive rats at 12 days after coarctation. In rats at 12 days after coarctation, the angiotensin II (10~6 M)-induced contraction of aortic rings with endothelium was attenuated by indomethacin and SQ29548 but not by CGS13080. These data suggest that a prostanoidmediated and endothelium-dependent mechanism of vasoconstriction contributes to the constrictor effect of angiotensin II in aortic rings of rats in the early phase of aortic coarctation-induced hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Release of endothelin-1, a novel potent vasoconstrictor peptide originally isolated from endothelial cells, from cultured bovine endothelial cells has been shown to be stimulated by arginine vasopressin and angiotensin II. To elucidate the cellular mechanism by which endothelin-1 is released by these vasoconstrictors, we tested the effects of several compounds on the agonist-induced endothelin-1 release and studied the changes of cytosolic free Ca2+ concentrations and phosphoinositide breakdown by these agonists in cultured bovine endothelial cells. Protein kinase C inhibitors (H-7, staurosporine), an intracellular Ca2+ chelator, and an inhibitor of phospholipase C (neomycin), all abolished the agonist-induced endothelin-1 release, whereas the Ca2+ channel blocker nicardipine was ineffective. Although synthetic 1,2-diglyceride (diolein) dose dependency stimulated endothelin-1 release, downregulation of protein kinase C after pretreatment with phorbol ester resulted in decreased effects to increase endothelin-1 release by the agonists. Both arginine vasopressin and angiotensin II induced immediate and transient increases in intracellular Ca2+ levels of fura-2-loaded endothelial cells as well as formation of inositol trisphosphate; the agonist-induced intracellular Ca2+ increases were not affected either by nicardipine or by chelating extracellular Ca2+. The arginine vasopressin- and angiotensin U-induced intracellular Ca2+ increases, inositol trisphosphate formation, and endothelin-1 release were completely abolished by V,-receptor antagonist and saralasin, respectively. It is concluded that arginine vasopressin and angiotensin II stimulate the release of endothelin-1 by a common mechanism, involving receptormediated mobilization of intracellular Ca2+ and activation of protein kinase C in endothelial cells.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

There are conflicting reports with regard to the antihypertensive effectiveness of interleukin-2 in the spontaneously hypertensive rat Recently, the original claim of a normalization of arterial pressure in the spontaneously hypertensive rat after a single administration of interleukin-2 has been disputed. Therefore, the present study was performed to determine whether the administration of interleukin-2 was effective in attenuating both the development and maintenance of hypertension in the spontaneously hypertensive rat Both young prehypertensive spontaneously hypertensive rats and adult spontaneously hypertensive rats with established hypertension received a single subcutaneous dose of 5,000 units/kg human recombinant interleukin-2. Arterial pressure was monitored at weekly intervals in both control and treated animals by the tail-cuff technique. Interleukin-2 administered as a one time single injection had no effect on the development of hypertension in the young animals or on the maintenance of hypertension in the adult animals. Interleukin-2 also was administered as a continuous infusion via osmotic minipumps at dose levels of 5,000 and 50,000 units/kg/wk to both young and adult spontaneously hypertensive rats. Continuous administration of interleukin-2 also had no effect on the development or maintenance of spontaneous hypertension. Therefore, this study firmly demonstrates that interleukin-2 has no effect on the onset or maintenance of hypertension in the spontaneously hypertensive rat

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Relations between platelet cytosolic calcium, parathyroid hormone, and blood pressure were investigated in 91 normotensive subjects: 47 men and 44 women ranging in age from 24 to 70 years. The men had higher mean arterial blood pressure, serum creatinine, and body mass index than the women. Serum total calcium, plasma ionized calcium, and parathyroid hormone (measured as both intact hormone and mid-molecule fragment) were not different between men and women; however, serum phosphate was higher in women than in men. Basal platelet cytosolic calcium was higher in men than in women (113.7±1.9 versus 105.9±1.7, respectively; p<0.0l), but there was no difference in the peak platelet cytosolic calcium responses to thrombin between the two groups. In the combined group of male and female subjects, platelet cytosolic calcium correlated with diastolic blood pressure and mean arterial pressure (r=0J7, p<0.001 and r=032,p<0.01, respectively). Intact parathyroid hormone correlated with systolic and mean arterial blood pressure (r=0.41,p<0.001 for both). Age correlated with both systolic blood pressure (r=0.40, p<0.001) and intact parathyroid hormone (r=0.51, p<0.001). When multiple regression analysis was performed using mean arterial pressure as the dependent variable, platelet cytosolic calcium and intact parathyroid hormone maintained significant correlations with mean arterial pressure. Platelet cytosolic calcium did not correlate with intact parathyroid hormone. These results suggest that both platelet cytosolic calcium and intact parathyroid hormone are associated with blood pressure regulation in normotensive subjects. However, the influences of these two factors on blood pressure are not interrelated.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The objectives of the present study were to determine whether increased sodium-lithium countertransport is associated with essential hypertension in the general Caucasian population and to determine whether this association is independent of the effects of gender, age, body size, and plasma lipids. We studied 543 men and 589 women from the population of Rochester, Minnesota. Mean sodium-lithium countertransport was higher in hypertensive than in normotensive subjects in men (370±147 [mean±SD] versus 315±110 jtmol/1 red blood cells [RBC]/hr, p<0.001) and in women (339±114 versus 269±92 fimol/l RBC/hr,p<0.001). Interindividual differences in plasma triglycerides, body mass index (wt/[ht]2), and plasma total cholesterol explained 13.0% of sodium-lithium countertransport variation in men (p<0.001) and 20.2% in women (p<0.001). Age did not predict additional sodium-lithium countertransport variation in either gender. Slopes of the regressions of sodium-lithium countertransport on plasma triglycerides, body mass index, and plasma total cholesterol did not differ between diagnostic groups in men (p=03l) or in women (p=0J29). After adjustment to remove sodium-lithium countertransport variation attributable to these covariates, mean sodium-lithium countertransport remained significantly higher in hypertensive than in normotensive subjects in men (354±139 versus 319±104 /i.mol/1 RBC/hr, p<0.01) and in women (311 ±103 versus 278±83 /imol/1 RBC/hr, p<0.01). These findings in a large sample from Rochester, Minnesota, support the conclusions that increased sodium-lithium countertransport is associated with essential hypertension in the general Caucasian population and that this association is independent of the effects of gender, age, body size, and plasma lipids. Additional studies are necessary to establish whether sodium-lithium countertransport is an independent predictor of risk of developing essential hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1991

数据来源: OVID