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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To assess the role of the vascular angiotensin II-generating system in one-kidney, one clip hypertension, we determined the angiotensin converting enzyme activity in plasma and vascular tissues and examined the pressor response to angiotensin II, angiotensin I, and tetradecapeptide renin substrate in isolated mesenteric arteries from one-kidney, one clip hypertensive rats 7 and 30 days after clipping the renal artery and in mesenteric arteries from age-matched normotensive rats. Angiotensin converting enzyme activity, determined in aortic and mesenteric tissues, was significantly augmented in the hypertensive (30 days after clipping) group, whereas plasma activity was normal. The vasoconstrictor responses elicited by angiotensin I and tetradecapeptide in arteries from hypertensive rats were found to be significantly potentiated 30 days after clipping, whereas the angiotensin II responses were basically unchanged. Saralasin completely blocked the vasoconstrictor responses, whereas captopril blocked only the responses to angiotensin I without affecting the responses elicited by angiotensin II and tetradecapeptide. Enalapril, an angiotensin converting enzyme inhibitor given intravenously to unanesthetized rats, significantly lowered the blood pressure of hypertensive rats. The pressor responses elicited by angiotensin II, angiotensin I, and tetradecapeptide were completely inhibited by saralasin, whereas enalapril blocked only the responses of angiotensin I but not those elicited by angiotensin II and tetradecapeptide. These results indicate that local formation of angiotensin II is increased in arteries of one-kidney, one clip hypertensive rats. The data obtained with tetradecapeptide renin substrate suggest an important role for nonrenin proteases in vascular angiotensin II formation.
Hypertension 1992 Jun
PMID:Increased vascular formation of angiotensin II in one-kidney, one clip hypertension. 131 51

We investigated the processing enzymes involved in the formation of circulating angiotensin-(1-7) after intravenous administration of angiotensin I to conscious spontaneously hypertensive and Wistar-Kyoto rats. Immunoreactive products, including angiotensin I, angiotensin II, and angiotensin-(1-7), were measured in arterial blood by three specific radioimmunoassays. Angiotensin I infusion (2 nmol) induced a rapid increase in immunoreactive angiotensin II and angiotensin-(1-7). Pretreatment with the angiotensin converting enzyme inhibitor enalaprilat (2 mg/kg) eliminated angiotensin II formation and augmented circulating levels of angiotensin I and angiotensin-(1-7) in spontaneously hypertensive and Wistar-Kyoto rats. The elevated levels of angiotensin-(1-7) in enalaprilat-treated rats were blocked by concurrent treatment with the neutral endopeptidase (EC 3.4.24.11) inhibitor SCH 39,370 (15 mg/kg) in both strains. Administration of SCH 39,370 alone decreased angiotensin-(1-7) levels in spontaneously hypertensive rats, whereas angiotensin II levels increased in both strains (p less than 0.01). Comparisons of the metabolism of angiotensin I in the two rat strains showed increased formation of angiotensin-(1-7) in spontaneously hypertensive rats not given any of the enzyme inhibitors. In addition, levels of angiotensin I were higher after administration of SCH 39,370 in hypertensive rats. These novel findings reveal that neutral endopeptidase EC 3.4.24.11 participates in the conversion of angiotensin I to angiotensin-(1-7) and in the metabolism of angiotensin II in the circulation of both spontaneously hypertensive and Wistar-Kyoto rats. Our results suggest that neutral endopeptidase EC 3.4.24.11 is a major enzymatic constituent of the circulating renin-angiotensin system.
Hypertension 1992 Jun
PMID:In vivo metabolism of angiotensin I by neutral endopeptidase (EC 3.4.24.11) in spontaneously hypertensive rats. 131 52

Vascular smooth muscle cell hypertrophy is a normal compensatory state that may play a pathogenic role in hypertension. Angiotensin II stimulates a hypertrophic response in cultured vascular smooth muscle cells. As part of the growth response, angiotensin II rapidly activates the Na(+)-H+ exchanger, increasing Na+ influx. Because Na+, K(+)-ATPase is the major cellular mechanism for regulating intracellular Na+, we studied the effects of angiotensin II-induced hypertrophy on Na+, K(+)-ATPase expression and activity. Angiotensin II caused rapid increases in both steady-state Na+, K(+)-ATPase activity (ouabain-sensitive 86Rb uptake) and intracellular [Na+]. Angiotensin II also caused a sustained increase in Na+, K(+)-ATPase at 24 hours with a 73% increase in maximal 86Rb uptake per milligram protein and a fourfold increase in Na+, K(+)-ATPase alpha-1 messenger RNA levels. Thus, angiotensin II hypertrophy was associated with rapid increases in Na+, K(+)-ATPase activity due to increased Na+ entry and sustained increases due to a specific increase in Na+, K(+)-ATPase expression. These data demonstrate dynamic regulation of Na+, K(+)-ATPase at the functional and molecular level and suggest that similar compensatory mechanisms should be present in vivo. Alterations in such compensatory pathways may be fundamental to the pathogenesis of hypertension.
Hypertension 1992 Aug
PMID:Na+, K(+)-adenosine triphosphatase regulation in hypertrophied vascular smooth muscle cells. 132 64

Left ventricular hypertrophy (LVH) is a common condition and a powerful independent risk factor for coronary heart disease, congestive heart failure, and other cardiac morbidity. It is associated with the male sex and advancing age. Its most common cause is hypertension, and many antihypertensive agents induce regression of LVH. Angiotensin-converting enzyme (ACE) inhibitors have been shown to reverse LVH by a mechanism as yet unknown. Reduction in afterload and other hemodynamic abnormalities by reduction of blood pressure is clearly a factor, but ACE inhibitors also block adrenergic action and other sympathetic nervous system influences, and the reduction in angiotensin II produces many effects. By inhibiting this potent vasoconstrictor and suppressing its degradation of the powerful vasodilator bradykinin, and by promoting sodium and water excretion, ACE inhibitors contribute to the restoration of normal ventricular function. Angiotensin II promotes protein synthesis in myocardial myocytes, and blocking this action may arrest the hypertrophic process. To determine the effect of angiotensin II on LVH and normalization of LV function, a study is now underway evaluating the effects of lisinopril, a new lysine analog of enalapril, and a diuretic agent in the treatment of hypertension LVH.
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PMID:ACE inhibitors and regression of left ventricular hypertrophy. 132 1

Renal tissue angiotensin I (Ang I) and II (Ang II) content and angiotensin converting enzyme activity were assessed in both kidneys during initial (7 days) and maintenance (25 days) phases of two-kidney, one clip hypertension in rats. At 7 and 25 days, systolic arterial pressure was 146 +/- 2 and 170 +/- 7 mm Hg, respectively. After 7 days, Ang I content of clipped kidneys was 64% and 70% higher (p < 0.001) than in nonclipped and sham-operated kidneys, respectively, when compared with levels in kidneys from sham-operated rats. In kidneys harvested 25 days after clipping one renal artery, Ang I and Ang II contents in clipped kidneys were increased 102% and 24% (p < 0.01), respectively. Ang II content was also 32% higher in nonclipped kidneys. Angiotensin converting enzyme activity in nonclipped kidneys was greater (p < 0.05) than that in either clipped (46% higher) or sham-operated kidneys (57% higher). Plasma Ang I and Ang II levels were elevated at 7 days but were not different at 25 days in clipped rats. These results demonstrate a dissociation between intrarenal and circulating levels of Ang I and Ang II and suggest that qualitatively different mechanisms may be responsible for the elevated intrarenal Ang II levels during the initial and maintenance phases of renal hypertension.
Hypertension 1992 Dec
PMID:Angiotensin and angiotensin converting enzyme tissue levels in two-kidney, one clip hypertensive rats. 133 45

1. Angiotensin converting enzyme (ACE)-inhibitors have been demonstrated to be effective in the treatment of cardiac hypertrophy when used in antihypertensive doses. The aim of our one year study with an ACE-inhibitor in rats was to separate local cardiac effects produced by a non-antihypertensive dose from those on systemic blood pressure when an antihypertensive dose was used. 2. Rats made hypertensive by aortic banding were subjected to chronic oral treatment for one year with an antihypertensive dose of the ACE inhibitor, ramipril 1 mg kg-1 daily, (RA 1 mg) or received a low dose of 10 micrograms kg-1 daily (RA 10 micrograms) which did not affect high blood pressure. 3. Chronic treatment with the ACE-inhibitor prevented left ventricular hypertrophy in the antihypertensive rats as did the low dose which had no effects on blood pressure. Similar effects were observed on myocardial fibrosis. Plasma ACE activity was inhibited in the RA 1 mg but not in the RA 10 micrograms group although conversion of angiotensin (Ang) I to Ang II in isolated aortic strips was suppressed in both treated groups. Plasma catecholamines were increased in the untreated control group, but treatment with either dose of ramipril normalized the values. The myocardial phosphocreatine to ATP ratio (an indicator of the energy state in the heart) was reduced in the vehicle control group whereas the hearts from treated animals showed a normal ratio comparable to hearts from sham-operated animals. 4. After one year, five animals were separated from each group, treatment withdrawn, and housed for additional six months. In the RA 1 mg group, blood pressure did not reach the value of the control vehicle group and surprisingly, left ventricular hypertrophy and myocardial fibrosis did not recur in animals during withdrawal of treatment.5. These data show that long term ACE inhibitor treatment with ramipril in antihypertensive and non-antihypertensive doses prevented cardiac hypertrophy and myocardial fibrosis. This protective effect was still present after 6 months treatment withdrawal.
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PMID:Ramipril prevents left ventricular hypertrophy with myocardial fibrosis without blood pressure reduction: a one year study in rats. 133 56

1. The angiotensin converting enzyme (ACE) activity of spontaneously hypertensive (SHR) and spontaneously hypertensive stroke-prone (SHRSP) rats was compared to the ACE activity of normotensive Wistar-Kyoto rats (WKY). 2. ACE activity was assessed indirectly in conscious unrestrained rats using the equipressor response end point to simultaneously calculate the extent of conversion of angiotensin I (AI) to angiotensin II (AII) and the pulmonary degradation of bradykinin (BK). 3. The pulmonary degradation of BK was significantly elevated (99.4%) in SHR rats whereas the elevation was not significant in SHRSP rats (99.2%) compared to WKY rats, even though the pulmonary inactivation of BK in WKY rats was higher (98.6%) than in normotensive Wistar rats (95.6% and 97.5%) previously studied. 4. Blood pressure responsiveness to intra-aortically injected BK (bolus injection and infusion) was markedly increased in SHR and SHRSP rats with no change in reactivity to sodium nitroprusside. 5. Conversion of AI to AII assessed by the equipressor doses of the hormones which produced a 20-mmHg rise in blood pressure was markedly elevated in SHR (86 +/- 4%) and SHRSP (80 +/- 7%) rats when compared to WKY rats (38 +/- 4%). 6. The marked increase in conversion of AI to AII in hypertensive animals, accompanied by an increased pulmonary degradation of BK in SHR rats, suggests that ACE activity is increased in conscious SHR and SHRSP rats and may participate in the genesis of hypertension in this model of genetic hypertension.
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PMID:Angiotensin converting activity assessed in vivo is increased in hereditary hypertensive rats. 134 16

One of the major consequences of hypertension is an increase in the thickness of the arterial medial smooth muscle cell layer. This has been shown in both large and medium size resistance vessels caused by smooth muscle cell hypertrophy. Both in vivo and in vitro data suggest that the vasoconstrictor peptide angiotensin II (Ang II) may play an important role in the development of the smooth muscle hypertrophy. We have demonstrated that Ang II, when added to quiescence cultures of vascular smooth muscle cells, results in the rapid induction of the early growth response genes c-fos, c-myc, and c-jun. This is due to new transcription as demonstrated by nuclear runoff transcription assay, but is not dependent on new protein synthesis, as it is not blocked by the addition of cycloheximide. The effect is due, however, to an increase in intracellular calcium, suggesting that any vasoconstrictor which results in an increase in intracellular calcium may act in this manner. Following the induction of the early growth response genes there is delayed induction of the platelet derived growth factor A-chain gene. Data from our laboratory and from that of others has shown in preliminary studies that blockade of either the Ang II-induced increases in c-fos or in the platelet-derived growth factor A-chain increases smooth muscle cell protein synthesis. This suggests that Ang II and other vasoconstrictors may play an important role in vascular smooth muscle growth, in hypertension and also in atherosclerosis and following balloon injury of the arterial wall.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of angiotensin II in vascular smooth muscle cell growth. 138 Jun 17

Angiotensin-converting enzyme inhibitors have been shown to be effective therapy for hypertension, and also for severe congestive heart failure, whether due to hypertension or to other causes. The reduction in cardiac hypertrophy that follows the use of these drugs is undoubtedly due in part to their favorable hemodynamic effects of reducing peripheral resistance and inducing venodilation. The same factors reduce cardiac dilation and left ventricular remodeling after myocardial infarction. The prevention of the hemodynamic effects of angiotensin II (Ang II) is probably the major factor in preventing end-organ damage, but there are some indications that Ang II may have an effect independent of blood pressure in promoting vascular hypertrophy. The separation of vasoconstrictor effects from any metabolic effects of Ang II is not easy, and final elucidation of the mechanisms involved is not yet available.
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PMID:Role of angiotensin-converting enzyme inhibitors in preventing or reducing end-organ damage in hypertension. 138 91

Factors that can influence cardiovascular growth are becoming increasingly important for our understanding of such complex diseases as cardiac hypertrophy, coronary artery disease, atherosclerosis, and hypertension. Several proto-oncogenes were found to be involved in the regulation of abnormal cell growth in cardiovascular disease. It is also evident that some peptide hormones, which are well known to be involved in blood pressure control, may play a role as growth modulators. Angiotensin II is one such peptide. It elevates blood pressure through its direct vasoconstrictor, sympathomimetic, and (through release of aldosterone) sodium-retaining activity but also appears to have mitogenic actions. Interestingly, all components of the renin-angiotensin system were found locally in cardiovascular tissues. The question remains whether angiotensin can act directly as a growth factor or whether it does so indirectly by influencing or modulating cell growth factors. A better understanding of the renin-angiotensin system as a direct or indirect mediator for cardiovascular hypertrophy would offer new and interesting insights into the pathophysiology of hypertension and possibly novel options for the treatment of cardiovascular disease.
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PMID:The molecular basis of cardiovascular hypertrophy: the role of the renin-angiotensin system. 138 95


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