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

The role of renin-angiotensin system has been examined in the maintenance of hypertension in acute and chronic two-kidney (36 weeks) and chronic one-kidney (12 weeks) Goldblatt hypertensive rats using three inhibitors of this system. The inhibitors used were URI-73A, a synthetic analog of lysophosphatidylethanolamine, which inhibits renin both in vivo and in vitro, SQ14,225, a potent converting enzyme inhibitor, and [Sar1, Thr8] angiotensin II, an angiotensin II antagonist. When the inhibitors were administered in acute (high renin) hypertensive rats, they all lowered blood pressure significantly. However, in the chronic (low renin) hypertensive phase, both renin and converting enzyme inhibitors lowered blood pressure, whereas, Sar1, Thr8 failed to lower blood pressure. The renin inhibitor lowered plasma renin activity (PRA), and SQ14,225 and [Sar1, Thr8] Ang II increased PRA. Further studies on water and electrolyte balance with one-kidney model hypertensive and uninephrectomized control rats showed no change in plasma volume. However, there was increased 24-hour urinary output and increased sodium excretion. This study indicates that in chronic renal hypertensive rats, blood pressure reduction is possible by either renin on converting enzyme inhibitor, but not by angiotensin antagonists. Since volume did not change either during the development or reversal of hypertension, volume did not appear to play a major role in the maintenance of hypertension.
Hypertension
PMID:Role of renin-angiotensin system in chronic renal hypertensive rats. 23 87

Hypertension is associated with cardiac hypertrophy, which is a structural adaptation of the heart in order to attenuate the systolic stress on the left ventricle. As cardiac myocytes cannot divide, they increase in mass and volume, probably by activating second messengers and proto-oncogenes involved in cellular differentiation and proliferation. Various mechanisms, such as pressure overload and angiotensin II (Ang II), have been proposed to trigger cardiocyte growth and left-ventricular hypertrophy (LVH). In both cases, activation of second messenger routes which increase the intracellular calcium concentration, protooncogene expression, and protein synthesis have been demonstrated. Ang II also facilitates the action of another trophic agent for cardiocytes, which is noradrenaline (NA). In addition, the prevention and reversal of LVH by inhibitors of angiotensin-converting enzyme (ACE) suggests a key role for Ang II. However, no conclusive evidence has demonstrated the role of a single pathophysiologic factor in LVH. Therefore, it is more attractive to suggest a link between high blood pressure, renin-angiotensin and other vasoactive systems, such as the adrenergic system, which might together lead in a synergistic way to cardiac hypertrophy.
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PMID:Mechanisms of cardiac growth. The role of the renin-angiotensin system. 129 8

The hypothesis that signal transduction mediated by platelet-derived growth factor (PDGF) and angiotensin II (Ang II) is altered in vascular smooth muscle (VSM) cells from the spontaneously hypertensive rat (SHR) was tested by measuring changes in the cytosolic free calcium concentration ([Ca2+]i). [Ca2+]i was measured in cultured aortic smooth muscle cells from SHRs and Wistar-Kyoto (WKY) normotensive rats using fura-2 as a calcium indicator and a microscopic digital image analysis system. Activation of cells with Ang II resulted in a prompt though transient rise in [Ca2+]i; the maximum increase was observed after 10-30-second intervals. On the other hand, activation of cells with PDGF BB produced an increase in [Ca2+]i with a 40-60-second lag period; the maximum increase was observed 2-4 minutes after the addition of PDGF. PDGF-stimulated increases in [Ca2+]i were markedly inhibited by the addition of the calcium channel antagonist verapamil (100 microM) as well as by removal of calcium from the extracellular bathing medium. However, Ang II-stimulated [Ca2+]i was not significantly affected by the addition of verapamil or by removal of extracellular calcium. These results would indicate that PDGF-mediated increases in [Ca2+]i in VSM cells are predominantly via Ca2+ influx, whereas Ang II-mediated increases are due to calcium release from intracellular pools. Basal and PDGF- and Ang II-stimulated increases in [Ca2+]i were significantly greater (p less than 0.05) in SHR VSM cells compared with WKY cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Feb
PMID:Altered signal transduction in vascular smooth muscle cells of spontaneously hypertensive rats. 131 Apr 80

Angiotensin II (Ang II) inhibits renin secretion and production from the kidney, but the effect of Ang II on adrenal renin is not clear. Nephrectomy, via elevated plasma adrenocorticotropic hormone (ACTH) and potassium, is a strong stimulator of adrenal renin production in the rat. This stimulation is inhibited by the infusion of Ang II, suggesting a negative feedback between Ang II and adrenal renin. In the present study, we examined the effect of Ang II on adrenal renin using a primary culture of rat glomerulosa cells. Cells were exposed to ACTH (10(-11) M), high potassium (8 and 12 mM), db-cyclic AMP (db-cAMP), (10(-3) M), or Ang II (10(-11) to 10(-5) M) for 24 hours, and active renin and inactive renin were measured. Active renin was predominant in the cells, whereas inactive renin predominated in the medium. Ang II stimulated renin production in a dose-dependent fashion (cell-active renin, 1.21 +/- 0.20 to 2.39 +/- 0.16; medium-inactive renin, 2.59 +/- 0.40 to 6.14 +/- 0.49 ng Ang I/10(6) cells). Both ACTH and db-cAMP significantly stimulated active renin in the cells (ACTH, 1.73 +/- 0.14 to 9.44 +/- 0.98; db-cAMP, 1.45 +/- 0.16 to 3.96 +/- 0.71 ng Ang I/10(6) cells) and inactive renin in the medium (ACTH, 4.98 +/- 0.38 to 43.7 +/- 5.63; db-cAMP, 3.80 +/- 0.32 to 33.55 +/- 5.62 ng Ang I/10(6) cells). The addition of Ang II (10(-7) M) blunted the stimulation of renin production by both ACTH and db-cAMP by 60%. High potassium-stimulated renin production was not inhibited by Ang II.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Mar
PMID:Effect of angiotensin II on renin production by rat adrenal glomerulosa cells in culture. 131 12

We examined the inhibitory effect of porcine C-type natriuretic peptide (CNP) on endothelin-1 secretion stimulated by thrombin and angiotensin II (Ang II) in cultured porcine endothelial cells. The results were compared with the effects of atrial (ANP) and brain (BNP) natriuretic peptides. Thrombin and Ang II produced a concentration-dependent stimulation of immunoreactive endothelin-1 secretion, and porcine CNP-22 potently inhibited this stimulated secretion in a concentration-dependent manner. CNP-22 had a stronger inhibitory effect than either porcine ANP(1-28) or porcine BNP-26. In addition, CNP potently increased the cellular level of cyclic guanosine 3',5'-monophosphate (GMP), with the inhibition of immunoreactive endothelin-1 secretion in response to thrombin and Ang II being paralleled by the increase in the cyclic GMP level. The increase of cyclic GMP produced by CNP was also greater than that due to porcine ANP(1-28) or porcine BNP-26. The immunoreactive endothelin-1 in the culture medium had two components on high-performance liquid chromatography; the major one corresponded to endothelin-1 (1-21) and the minor one to big endothelin-1 (porcine 1-39). Treatment with CNP did not affect this profile. Our results suggest that CNP probably inhibits the endothelin-1 secretion stimulated by thrombin and Ang II through a cyclic GMP-dependent process. The increase of cyclic GMP levels and the inhibition of immunoreactive endothelin-1 secretion produced by CNP appear to be greater than those produced by ANP or BNP.
Hypertension 1992 Apr
PMID:C-type natriuretic peptide inhibits thrombin- and angiotensin II-stimulated endothelin release via cyclic guanosine 3',5'-monophosphate. 131 93

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

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

We investigated pressor sensitivity to infused phenylephrine (PE), 0.05 to 0.4 micrograms/kg/min, and angiotensin II (Ang II), 2.5 to 10 ng/kg/min, in 35 patients with mild-to-moderate hypertension, before and at the end of a 4-week treatment period with the angiotensin-converting enzyme (ACE) inhibitor, cilazapril, 2.5 or 5.0 mg/day. Cilazapril lowered the mean systolic and diastolic blood pressure by 10.6/3.5 mm Hg, but had no effect on the dose-response curves of dose of PE or Ang II vs. the increase in systolic, diastolic, or mean blood pressure, or heart rate. There were also no significant effects of cilazapril on PD20 values, i.e., the dose of PE or Ang II required to increase mean arterial blood pressure (MAP) by 20 mm Hg, or on delta R-R/delta MAP (ratio of the increase of the ECG R-R interval to the increase in mean arterial blood pressure) as a measure of baroreflex sensitivity. Plasma renin activity was significantly increased by cilazapril therapy, but there were no changes in plasma concentrations of Ang II or atrial natriuretic factor. We conclude that cilazapril, an ACE inhibitor, does not alter alpha 1-adrenoceptor and Ang II receptor sensitivity to selective agonists, nor does it affect baroreflex sensitivity.
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PMID:Alpha-adrenergic and angiotensin II pressor sensitivity in hypertensive patients treated with an angiotensin-converting enzyme inhibitor. 138 57


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