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

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

Bovine albumin (BA: 2 mg/kg-1, i.v.) produced a fall in systemic arterial blood pressure accompanied by central venous hypertension and bradycardia in pentobarbital-anaesthetized, spontaneously breathing, bovine albumin-sensitized adult domestic fowl. Trasylol (a potent inhibitor of kallikreins) suppressed acute systemic anaphylaxis. Polyphloretin phosphate (an effective antagonist of PGF2alpha) also inhibited the cardiovascular responses to antigen and PGF2alpha. Sodium meclofenamate and phenylbutazone showed varying degree of blockade of cardiovascular responses to exogenously administered chemical mediators (bradykinik, PGF2alpha, SRS-A and to a lesser extent of histamine, 5-HT and acetylcholine) and antigen. Indomethacin (virtually devoid of receptor blocking activities toward exogenously injected chemical mediators) inhibited anaphylaxis. The results of this investigation strongly suggested an important role of vasoactive lipids and polypeptides in avian anaphylaxis.
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PMID:Acute systemic anaphylaxis in adult domestic fowl--possible role of vasoactive lipids and peptides. 31 23

The prostaglandin synthetase inhibitor indomethacin was given orally or intravenously to pregnant ewes. This resulted in the fetal pulmonary to systemic arterial mean blood pressure difference across the ductus arteriosus rising significantly, presumably secondary to constriction of the ductus arteriosus. The pressure difference was due to pulmonary arterial hypertension, and not due to a fall in systemic arterial mean blood pressure. Fetal arterial blood gas tensions and pH values were normal throughout. In five experiments the pressure difference could be promptly but temporarily reversed by the administration of PGE1 into the fetal inferior vena cava. Indomethacin was present in fetal blood, and maternal plasma prostaglandin levels were suppressed. Indomethacin administration during pregnancy causes constriction of the fetal ductus arteriosus and fetal pulmonary arterial hypertension which, if severe, may cause rapid fetal death. It is possible that this mechanism may be one cause of persistent pulmonary hypertension or tricuspid insufficiency or both in the newborn infant.
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PMID:Constriction of the fetal ductus arteriosus after administration of indomethacin to the pregnant ewe. 43 Mar 14

The prostaglandin synthetase inhibitor indomethacin was given orally or intravenously to pregnant ewes. This resulted in a significant rise in the fetal pulmonary-to-systemic arterial mean blood pressure difference across the ductus arteriosus, presumably secondary to constriction of the ductus arteriosus. In five experiments the pressure difference could be promptly but temporarily reversed by the administration of prostaglandin E1 (PGE1) into the fetal inferior vena cava. Fetal lungs from study and control animals were fixed by perfusion at measured pulmonary arterial mean blood pressure, and fifth-generation resistance vessels were studied. The medial width/external diameter ratio was significantly increased in the study vs the control lungs due to increased smooth muscle and decreased external diameter. In addition, study fetuses had acute degenerative myocardial changes in the tricuspid valve papillary muscles, the right ventricular free wall and the interventricular septum. Similar changes were not seen in control fetuses. Indomethacin administration during pregnancy causes constriction of the fetal ductus arteriosus, fetal pulmonary arterial hypertension, and right ventricular damage. If severe, this may cause rapid fetal death. If less severe, in the newborn infant, this mechanism may be one cause of persistent pulmonary hypertension due to vasoconstriction and increased pulmonary arterial smooth muscle and/or tricuspid insufficiency due to papillary muscle infarction.
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PMID:Hemodynamic, pulmonary vascular, and myocardial abnormalities secondary to pharmacologic constriction of the fetal ductus arteriosus. A possible mechanism for persistent pulmonary hypertension and transient tricuspid insufficiency in the newborn infant. 44 54

A 2-year-old girl presenting with features of both Bartter's syndrome and renal tubular acidosis was investigated. Hypokalemia, increased plasma renin activity in the absence of hypertension, insensitivity to the pressor effects of angiotensin and a histological picture of juxtaglomerular hyperplasia were characteristic of Bartter's syndrome, but an unusual finding was the presence of metabolic acidosis instead of alkalosis. Functional studies revealed a proximal tubular defect in sodium and bicarbonate reabsorption and a distal defect in sodium reabsorption, urinary acidification and concentrating mechanism. Indomethacin administration was followed by an excellent clinical response and improvement of most functional abnormalities. The defect in distal sodium reabsorption was, however, not corrected by prostaglandin inhibition, and could represent the primary event leading to potassium wasting and secondary hypersecretion of prostaglandins.
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PMID:Bartter's syndrome presenting with features resembling renal tubular acidosis. Improvement of renal tubular defects by indomethacin. 65 58

Indomethacin inhibits the synthesis of prostaglandin and the release of renin. These effects were studied in normal rabbits and rabbits with two-kidney Goldblatt hypertension (2KGH) and one-kidney Goldblatt hypertension (1KGH) by giving daily intravenous injections of indomethacin (3mg/kg after two initial doses of 9 mg/kg), and in appropriate control rabbits given diluent phosphate buffer without indomethacin. In normal rabbits, indomethacin significantly decreased immunoreactive plasma prostaglandin E-like substance (IPGE) and plasma renin activity (PRA). Indomethacin did not change plasma creatinine (PCr) or mean blood pressure but it decreased renal blood flow (RBF) and glomerular filtration rate (GFR). In 2KGH rabbits, responses depended on the level of renal function and, to a lesser extent, on the level of PRA. In six of10 2KGH rabbits in which hypertension developed without significant changes in PRA, IPGE, PCr, RBF, and GFR, indomethacin produced changes similar to those seen in normals. In the other four rabbits, development of 2KGH was accompanied by increased PRA, increased IPGE, and decreased RBF and GFR, and indomethacin produced renal failure, oliguria, malignant hypertension, and death within 5 days. In 1KGH rabbits, indomethacin decreased IPGE, PRA, and renal function but increased mean blood pressure. These observations suggest that prostaglandins exert a protective effect on renal function in renovascular hypertension.
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PMID:The effect of indomethacin blockade of prostaglandin synthesis on blood pressure of normal rabbits and rabbits with renovascular hypertension. 83 Apr 37

The effects of prostaglandin E2 (PGE2) and a prostaglandin inhibitor, indomethacin, on the development of adrenal regeneration hypertension (ARH) were investigated. Weanling female rats underwent right adrenonephrectomy and left adrenal enucleation. PGE2 was injected subcutaneously daily in dosages of 0, 20, 40 and 80 mug/day. Indomethacin, 1 mg/kg, was administered twice daily by gavage. Blood pressures were determined by a tail and cuff plethysmographic method at 3, 5, and 7 wk after surgery. Increases in dosage of PGE2 produced a progressive reduction in mean blood pressures, heart, and kidney weights. Indomethacin produced significant increases in mean blood pressure, heart, kidney, and adrenal weights. The effects of aspirin and indomethacin on the blood pressures of rats with right adrenalectomy, left adrenal enucleation, and intact kidneys were studied. Administration of asprin twice daily (25 or 50 mg/kg) produced a fall in blood pressure, body and heart weight. Administration of 1 mg/kg twice daily of indomethacin resulted in a significant increase in blood pressure at 3 wk, and 0.1 or 1 mg/kg caused significant increases at 5 wk. The heart, kidney, and adrenal weights also showed increases with indomethacin administration. This study suggests that a deficiency of renal PGE2 may be involved in the etiology of ARH.
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PMID:Effects of prostaglandin E2 and prostaglandin inhibitors on adrenal regeneration hypertension. 84 31

1. The hypothesis that suppression of prostaglandin E (PGE) synthesis by indomethacin exacerbates renal clip hypertension in the rat was investigated. 2. Indomethacin exacerbated hypertension in renal clip rats. 3. In vitro PGE synthesis determined by gas liquid chromatography (GLC) was suppressed in medullary tissue from the hypertensive animals irrespective of indomethacin treatment. 4. The findings support the concept that PGs participate in blood pressure regulation in experimental renal hypertension.
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PMID:Renal prostaglandin synthesis in experimental renal clip hypertension in the rat. 98 62

1. Indomethacin inhibits prostaglandin synthesis and interferes with renin release; these effects were studied in rabbit renovascular hypertension. 2. Ten intravenous injections (3 mg day-1 kg-1 after two initial doses of 9 mg/kg) of indomethacin were given daily to ten normal rabbits, ten rabbits with two-kidney Goldblatt hypertension (2KH), tension (1KH). Twelve appropriate control rabbits received diluent phosphate buffer without indomethacin. Plasma renin activity and plasma prostaglandin E2 were measured by radioimmunoassay. 3. In the normal group, indomethacin significantly decreased plasma prostaglandin E2 (1-15 to 0-2 ng/ml, SEM 0-2; P less than 0-01) and plasma renin activity (20 to 3 ng h-1 ml-1, SEM 1, P less than 0-01). Plasma creatinine increased slightly but the mean blood pressure was not significantly changed by indomethacin. 4. Six of ten rabbits with 2KH showed results similar to those in the normal rabbits. In four of ten rabbits in which development of 2KH was accompanied by increments in plasma renin activity (18 to 31-5 ng h-1 ml-1, SEM 3 and 4 respectively; P less than 0-01) and plasma prostaglandin E2 (1-2 to 3-4 ng/ml, SEM 0-2 and 0-4 respectively; P less than 0-05), treatment with indomethacin produced renal failure (plasma creatinine increasing to 7-6 mg/100 ml), oliguria, malignant hypertension (mean blood pressure, 168 mmHg, SEM 7-7) and death within 5 days. 5. In 1KH, indomethacin decreased plasma renin activity and plasma prostaglandin E2, but caused increased mean blood pressure (102 to 121 mmHg, SEM 4 and 6 respectively; P less than 0-01) and decreased renal function (plasma creatinine 0-9 +/- 0-04 to 3-5 +/- 1 mg/100 ml, SEM 0-04 and 1 respectively; P less than 0-01). 6. Aggravation of hypertension was conditioned by pre-existing levels of renal function and, to a lesser extent, by plasma renin activities. 7. These results suggest that prostaglandins exert a protective effect on renal function in renovascular hypertension.
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PMID:Effects of indomethacin in rabbit renovascular hypertension. 107 20

1. The role of renal medullary prostaglandin E has been examined in rats with hypertension induced by sodium chloride and deoxycorticosterone (salt-DOC). 2. Synthesis of prostaglandin E was normal in early salt-DOC hypertension. Indomethacin exacerbated the hypertension, and depressed synthesis of prostaglandin E equally in hypertensive and control rats. 3. Synthesis of prostaglandin E was depressed in rats with late salt-DOC hypertension. 4. The results lend support to the concept that prostaglandin E is involved in the regulation of arterial pressure.
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PMID:Renal prostaglandin synthesis in hypertension induced by deoxycorticosterone and sodium chloride in the rat. 107 21


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