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)

Saralasin is a highly soluble and stable AII antagonist with a relatively short half-life; therefore, its effects are rapidly reversible when administered i.v. Acute and subacute studies have shown only transient toxicosis with no significant pathology or teratology. Saralasin's angiotensin receptor affinity has been correlated with its biologic acitivity. Observations from the pharmacodynamic investigations have shown that saralasin is a specific competitive antagonist of the vascular, renal, adrenal, cardiac, and central nervous system actions of AII. In addition, these studies further support the utility of saralasin as a diagnostic and therapeutic agent for patients whose hypertension is due directly to AII.
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PMID:Preclinical pharmacology of saralasin. 11 8

The angiotensin antagonist, saralasin, (10 and 30 mg/kg), increased serum renin activity (SRA) in normal, conscious rats from 2.7 +/- 0.4 to 16.2 +/- 3.7 and 22.5 +/- 2.4 ng/ml/hr (p less than 0.001), respectively, without markedly altering blood pressure or heart rate. Indomethacin, in a dose which inhibited the urinary excretion of prostaglandin E2 (PGE2) by 75%, and arachidonate-induced hypotension by 83%, failed to alter basal SRA but inhibited saralasin-induced renin release by 99% and 87% at the 10 and 30 mg/kg doses, respectively. Indomethacin failed to alter basal hemodynamics or the hemodynamic response to saralasin. Propranolol (1.5 mg/kg) inhibited saralasin-induced renin release by 93% and enhanced the suppressant effect of indomethacin from 79% to 100%. Meclofenamate, another prostaglandin synthesis inhibitor, also blocked saralasin-induced renin release by 99% and 72% at the 10 and 30 mg/kg doses, respectively (p less than 0.001). In sodium-depleted rats, saralasin (0.3 mg/kg) increased SRA from 12 +/- 2 to 119 +/- 6 ng/ml/hr (p less than 0.001) and decreased blood pressure by 6% (p less than 0.01). In these animals, indomethacin failed to alter basal SRA, but inhibited saralasin-induced renin release by 82%, urinary excretion of PGE2 by 79%, and arachidonate-induced hypotension by 81%. These findings suggest 1) that saralasin-induced renin release is mediated by renal prostaglandins, and 2) an interrelationship exists between the receptor controlling AII-mediated inhibition of renin release, which is blocked by saralasin, and the juxtaglomerular beta-adrenergic receptor.
Hypertension
PMID:Saralasin-induced renin release: its blockade by prostaglandin synthesis inhibitors in the conscious rat. 12 Mar 20

The mechanism by which the angiotensin I (AI) converting enzyme inhibitor SQ20,881 (less than Glu-Trp-Pro-Arg-Pro-Glu-Ile-Pro-Pro) blocks the pressor response to exogenous AI was studied in vivo in the intact anesthetized dog. When administered as a single dose 250 times that of injected AI (250 nmoles/kg) into either the pulmonary or systemic circulation, SQ20,881 produced inhibition of pulmonary conversion of exogenous AI to AII that lasted for more than 6 hours as judged by the absence of immunoreactive or labeled AII in the pulmonary venous effluent. In contrast, the pressor response to exogenous AI began to reappear within 1 hour of SQ20,881 administration. Six hours following SQ20,881, the pressor response to AI had nearly returned to normal, still in the absence of demonstrable intrapulmonary conversion and without release of detectable amounts of AII into the pulmonary venous effluent. These experiments demonstrated that AI has a pressor effect in the presence of SQ20,881 that is independent of pulmonary conversion. Studies with (Des-Asp) AII and (Des-Asp, Arg) AII showed that the delayed pressor response to AI following SQ20,881 administration could not be accounted for by circulating peptide metabolites of AI or AII. A competitive inhibitor of AII, (D-Asp, Ile) AII completely blocked the returning pressor response, suggesting that extrapulmonary generation of AII was responsible. The data strongly suggest that the systemic vascular bed taken as a whole contains large amounts of AI converting enzyme that is capable of rapid generation of AII without releasing the peptide into circulation. The extrapulmonary enzyme is more resistant to long-lasting blockade by SQ20,881 than pulmonary converting enzyme. The physiological role of extrapulmonary conversion systemic and local circulatory homeotasis remains to be assessed.
Hypertension
PMID:Mechanism of angiotensin I converting enzyme inhibition by SQ20,881 (less than Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro) in vivo. Further evidence for extrapulmonary conversion. 23 89

Twenty-four conscious male Wistar rats with hypertension induced by left renal artery clipping (two-kidney hypertension) were infused intravenously with 1-Sar-8-Ala-angiotensin II a competitive angiotensin II antagonist. The spectrum of responses was wide, ranging from a mild elevation in blood pressure to a marked fall in blood pressure, despite effective and specific angiotensin blockade in all cases. The change in blood pressure during 1-Sar-8-Ala-AII infusion activity showed a significant correlation with the level of plasma renin prevailing immediately before the infusion (r = - 0.78, P less than 0.01) but not with the prevailing blood urea level (r = 0.27, 0.1 greater than P greater than 0.05), the drgree of hypertension (r = 0.42, 0.1 greater than P greater than 0.05), or the time since clipping (r = 0.02, P greater than 0.05). There was no significant correlation between the degree of hypertension and the plasma renin activity (r = 0.42, 0.1 greater than P greater than 0.05). In rats with blood pressure drops greater than 20 mm Hg in response to 1-Sar-8-Ala-AII, the final blood pressure level was still above the normotensive range. Excision of the clipped kidney reduced blood pressure to normal or to near normal within 24 hours in all of the rats tested. It is concluded that the degree of dependence of renal hypertension on the renin-angiotensin system is directly related to the increase in circulating angiotensin itself and not to an increase in sensitivity to angiotensin. Other factors appear to be involved in renal clip hypertension in addition to circulating renin and angiotensin, especially when the measured activity of plasma renin is normal.
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PMID:Effect of the angiotensin II blocker 1-Sar-8-Ala-angiotensin II on renal artery clip hypertension in the rat. 119 61

During a double-blind, randomized study in hypertensive patients, changes in blood pressure (BP) and in plasma lipid and lipoprotein levels during treatment with celiprolol were compared with those occurring during nifedipine treatment. Fifty-three patients (28 men and 25 women) with mild-to-moderate hypertension, aged 20-64 years, were studied. After a 1-month placebo run-in period, patients were randomly assigned to receive either nifedipine (40 mg daily) or celiprolol (200 mg daily) each time using a double dummy technique. After 6 weeks, dosages of each drug could be doubled. Both drugs caused similar reductions in blood pressure but after 12 weeks treatment, the percentage of decrease in diastolic BP (DBP) was more pronounced (p less than 0.01) in the nifedipine group (-18%) than in the celiprolol group (-12%). After 6 weeks, there were no differences in plasma lipids between the two treatment groups. However, the changes after 12 weeks treatment were different (p less than 0.05) between the groups, leading to lower levels of plasma esterified cholesterol, low-density lipoprotein (LDL) cholesterol and apoprotein AI, AII, and B in the celiprolol group. Plasma lecithin cholesterol acyltransferase activity (LCAT) was not modified, suggesting that reverse cholesterol transport was not affected by the drugs. In both treatment groups, a significant positive relationship was observed between changes in LDL cholesterol and apoprotein B. As compared with nifedipine, celiprolol after 12-week therapy had a rather favorable plasma lipid profile. The clinical relevance of such findings, in terms of prevention of cardiovascular complications, has yet to be established.
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PMID:Comparison of the effect of celiprolol and nifedipine on blood pressure and plasma lipids. 138 Oct 18

Juxtaglomerular (JG) cells on the acute phase in two-kidney Goldblatt hypertensive (2KGH) rats and spontaneously hypertensive rats (SHR) were examined immunohistochemically. JG cells in 2KGH rats and SHR were positively stained with anti-renin serum and anti-angiotensin II (A II) serum. In 2KGH rats, the number of renin and AII immunoreactive JG cells in the clipped kidneys increased throughout the observation period. The number of renin and AII immunoreactive JG cells in the unclipped kidneys was almost the same as that in control rats, although immunoreactivity of these cells was weak and they were small in size. These changes in the unclipped kidneys became obvious with the time course after operation. We did not see any changes in these cells in SHR. In 2KGH rats treated with captopril, the number of renin immunoreactive JG cells in the clipped kidneys increased, whereas that of AII immunoreactive JG cells in the bilateral kidney decreased. When captopril was administered to SHR, the number of renin immunoreactive JG cells in the bilateral kidney increased, whereas that of AII immunoreactive JG cells in the bilateral kidney decreased. These results suggested that the JG cell in the bilateral kidney was closely related to the development of hypertension in 2KGH rats, but not in SHR. The increase of renin immunoreactive JG cells in 2KGH rats and SHR treated with captopril was probably due to the removal of negative feedback inhibition of AII on JG cells.
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PMID:Immunohistochemical findings of juxtaglomerular cells on acute phase in two-kidney Goldblatt hypertensive rats and spontaneously hypertensive rats. 142 May 65

We investigated the effects of the traditional Chinese herbal drugs, Dai-saiko-to (D) and Saiko-ka-ryukotsuboreito (S) on blood pressure, pulse rates, serum lipids, lipoproteins and apolipoproteins in 30 patients with mild to moderate hypertension in an open, randomised trial. After the drug treatment, BP remained unchanged, but pulse rates declined significantly after 3 months in the S treated group. Serum total cholesterol and triglyceride values did not change, but high density lipoprotein-cholesterol increased significantly (P < 0.05) in both groups. Apo-AI (P < 0.1 in S group) and apo-AII (P < 0.05 in D group, P < 0.1 in S group) tended to increase 3 months after treatment. These data indicate that both of these traditional Chinese medicines have a preferential effect on lipid metabolism with little antihypertensive action.
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PMID:Effects of Chinese herbal drugs on serum lipids, lipoproteins and apolipoproteins in mild to moderate essential hypertensive patients. 146 97

Interest in effects of oral calcium (Ca) on blood pressure is now generally focused on salt-induced hypertension. In this study hemodynamic effects of long-term high oral Ca were examined in two different genetic models of salt-sensitive hypertension, stroke-prone spontaneously hypertensive rats (spSHR) and Dahl salt-sensitive (DS) hypertensive rats. High vs low oral Ca (2.0 vs 0.4% Ca, 8-13 rats/diet) significantly (p less than 0.05) attenuated salt-induced hypertension (7% NaCl intake) in female spSHR (mean arterial pressure = 137 vs 175 mmHg) but aggravated such hypertension in female DS rats (141 vs 124 mmHg). Pressor responsiveness to norepinephrine (NE) and angiotensin (A) II were examined in the same rats. High oral Ca decreased pressor responses to graded intravenous injections of NE and AII in spSHR and increased such responses in DS rats. In spSHR, the decreased pressor responsiveness preceded the antihypertensive effect of high oral Ca. In summary, 2.0 vs 0.4% oral Ca produces contrasting effects on blood pressure in two genetic models of salt-sensitive hypertension (stroke-prone SHR and Dahl salt-sensitive rats). These contrasting effects on blood pressure may be related to differential effects of oral Ca on vascular responsiveness to endogenous vasoconstrictors in these two genetic models of salt-sensitive hypertension.
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PMID:Contrasting hemodynamic effects of high oral calcium in genetic models of salt-sensitive hypertension. 177 4

To determine the possible role of a glycaemic control in lipid metabolism in non-insulin-dependent diabetes mellitus (NIDDM) patients, serum lipid and apolipoprotein levels were measured in well-controlled and poorly controlled lean NIDDM without proteinuria and hypertension. A sample of 96 lean NIDDM patients (body mass index less than 25 kg m-2 in men and less than 27 kg m-2 in women) were divided into two groups: group I, where the HbA1c concentration had been less than 6% for the previous 3 months, and group II, where the HbA1c concentration had been greater than 8% for the previous 3 months. Serum total cholesterol, triglyceride, and HDL-cholesterol levels showed no significant differences between groups I and II. Furthermore, serum levels of apolipoproteins AI, AII, B, CII, CIII, and E did not differ significantly between groups I and II. These results suggest that glycaemic control did not influence lipid metabolism in lean NIDDM patients.
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PMID:Serum lipid and apolipoprotein levels in non-hypertensive lean NIDDM patients. 186 64

To evaluate the effects of endothelin-1 (ET-1) on tumor blood flow, the authors measured the mean arterial blood pressure (MABP) of enflurane-anesthetized male Donryu rats and the tissue blood flow of subcutaneously implanted tumor (Yoshida rat ascites hepatoma LY-80) by using a hydrogen clearance method. The tumor blood flow was evaluated in terms of the ratio to the maximum blood flow, which was defined as the largest flow in the same position during successive measurements. After bolus intravenous administration of ET-1 (1.0 nmol/kg), MABP reached approximately 140 mmHg (at 5-30 min), diminishing gradually to the baseline level over 2 h. The tumor blood flow increased from 36.7 +/- 20.6 to 59.5 +/- 30.2% (n = 32, P less than 0.001, at 2 min), returning to the baseline level at 10 min. On the other hand, at 2 min after the beginning of continuous intravenous infusion of [Asp1, Ile5]-angiotensin II (AII; the dose was determined by a blood pressure control system for keeping MABP at approximately 150 mmHg, consequently 0.26 micrograms/kg/min on the average), the tumor blood flow increased from 42.3 +/- 21.6 to 76.4 +/- 22.6% (n = 32, P less than 0.001), which was significantly larger than the flow after ET-1. The results indicate that hypertension induced by systemic ET-1 injection is less effective than hypertension induced by continuous systemic AII infusion in increasing tumor blood flow; AII is probably a suitable agent as a safe and effective enhancer of tumor blood flow. Moreover, ET-1 appears to constrict arterial vessels in the microcirculation time-dependently, while AII constricts probably only normal peripheral arterioles.
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PMID:Comparison of the effects of intravenously bolus-administered endothelin-1 and infused angiotensin II on the subcutaneous tumor blood flow in anesthetized rats. 191 32


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