Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal prostaglandins (PG) appear to mediate renin release due to stimulation of the intrarenal baroreceptor, but not that due to activation of the macula densa. However, as the role of PG in sympathetically mediated renin release remains unclear, a possible interrelationship between these factors was examined in conscious rats. Hydralazine increased the serum renin levels from 3.1+/-0.8 to 16.7+/-3.0 ng/ml per h at a dose of 1 mg/kg. Indomethacin (5 mg/kg) suppressed urinary PGE(2) and PGF(2alpha) excretion by 89 and 74%, respectively, arachidonate hypotension by 82%, and inhibited the elevated renin levels from hydralazine by 100% without altering the hypotensive effect of the drug. Another PG synthetase inhibitor, meclofenamate, was also effective in attenuating hydralazine-induced renin release, urinary PGE(2) and PGF(2alpha) excretion, and arachidonate hypotension. Isoproterenol, a nonselective beta-adrenergic agonist, increased heart rate, lowered blood pressure, and also stimulated the release of renin when administered intraperitoneally. However, intrarenal infusion of the drug only resulted in increased renin release. Indomethacin inhibited isoproterenol-induced renin release by 66 and 67%, respectively, without altering the hemodynamic effects associated with the intraperitoneal administration of the drug. The selective beta(1) agonist, H133/22, increased the release of renin and heart rate in a dose-related manner without altering blood pressure. H133/22-induced renin release was inhibited by 80% by indomethacin pretreatment. Finally, intrarenal infusions of dibutyryl cyclic AMP (3 mg/kg per min) increased the serum activity from 4.1+/-0.2 to 20.4+/-3.9 ng/ml per h without altering mean arterial pressure. Indomethacin inhibited this renin response to dibutyryl cyclic AMP by 96%. Thus, renal PG appear to be important mediators of sympathetically stimulated renin release acting as a site distal to the beta-adrenergic receptor.
 ...
PMID:Role of renal prostaglandins in sympathetically mediated renin relase in the rat. 3 56

Four patients with idiopathic orthostatic hypotension (I.O.H.) and one with postural hypotension and diabetes were studied. Plasma-renin activity (P.R.A.) was low and did not rise appropriately with salt restriction and diuretic stimulation. Aldosterone levels were normal and rose with diuretic therapy. Plasma-volume, plasma dopamine beta-hydroxylase, urinary catecholamines, metanephrines, and vanillyl mandelic acid (V.M.A) were normal. Treatment with indomethacin (75-150 mg/day) raised the upright blood-pressure (B.P.) by an average of 20-30 mm Hg diastolic and allowed the four patients with I.O.H. to walk about without orthostatic symptoms but it had no effect in the fifth patient. When indomethacin was discontinued in one patient who had been taking it for 9 months with symptomatic relief, the B.P. fell to pretreatment levels within 48 h. When indomethacin was reinstituted the B.P. rose again. Indomethacin was more effective in these patients than either propranolol or fludrocortisone. There may be an absolute or relative excess of certain vasodepressor prostaglandins in the peripheral vessels which results in pooling of blood and orthostatic hypotension. If this is the case indomethacin might improve the orthostatic symptoms of I.O.H. by its inhibitory effect on prostaglandin synthesis, but its mechanism of action remains to be determined.
 ...
PMID:Treatment of idiopathic orthostatic hypotension (Shy-Drager syndrome) with indomethacin. 7 34

Three patients suffering from Bartter's syndrome were studied before and after 5 days of treatment with the prostaglandin synthetase inhibitors, aspirin and indomethacin. Saralasin was given by intravenous infusion in increasing doses from 0.6 to 42 micrograms/min.kg/BW. During saralasin infusion a blood pressure reduction was observed in all patients. Aspirin treatment did not affect this response and nor did it affect other manifestations of the syndrome. Indomethacin treatment changed the blood pressure response to saralasin in such a way that the blood pressure was increased in one patient and was unchanged in the other. Indomethacin also tended to normalize other features of Bartter's syndrome, such as the hyperreninaemia and angiotensin unresponsiveness, but did not affect the hypokalaemia. The saralsin effect on blood pressure is thus evidently inversely related to the prevailing activity of the renin-angiotensin system in this condition also, and the patients obviously depended on the renin-angiotensin system to maintain their blood pressure. Our findings, together with data in the literature, indicate that angiotensin unresponsiveness of the vascular bed is not a primary feature in Bartter's syndrome. Chloride loss is currently thought to be the basic abnormality and this may link the Bartter's syndrome with other diseased states characterized by chloride loss, such as the syndrome of habitual vomiting and chronic treatment with loop diuretics.
 ...
PMID:Effect of Sar1-ala8-angiotensin II on blood pressure and renin in Bartter's syndrome, before and after treatment with prostaglandin synthetase inhibitors. 11

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.
 ...
PMID:Saralasin-induced renin release: its blockade by prostaglandin synthesis inhibitors in the conscious rat. 12 Mar 20

1. Six essential hypertensive patients (five with low renin) were treated in successive weeks with placebo; hydrochlorothiazide 100 mg (382 micromol)/day; hydrochlorothiazide and 50 mmol of sodium/day diet; hydrochlorothiazide, 50 mmol of sodium diet and propranolol 160 mg (544 micromol)/day; and hydrochlorothiazide, 50 mmol of sodium and indomethacin 100 mg (287 micromol)/day. 2. Although blood pressure remained unchanged and serum potassium fell on diuretic with or without low salt, there was a marked increase of active renin and a lesser increase of inactive renin, resulting in an increased proportion of active to total renin. 3. Propranolol decreased both active and inactive renin, but not significantly. 4. Indomethacin produced a marked suppression of active renin, a smaller reduction in inactive renin, and a reduction of the ratio of active to total renin almost to placebo values. 5. Blood pressure rose to control values on indomethacin despite the fall in renin whereas it fell with propranolol with little change in renin. 6. Serum aldosterone rose with stimulation but remained elevated despite effective renin suppression with indomethacin and continuing reduced serum potassium concentration.
 ...
PMID:Acid-activated renin responses to hydrochlorothiazide, propranol and indomethacin. 28 43

1. Indomethacin was administered alone or in addition to either diuretic or propranolol therapy to three groups of patients with essential hypertension on a free sodium diet. 2. Indomethacin administration reduced renin secretion by about 30% in untreated uncomplicated hypertensive patients and by about 75% in those whose renin secretion had either been stimulated or suppressed by maintained diuretic or beta-adrenoreceptor-blockade therapy. 3. Indomethacin administration produced no net effect on blood pressure in untreated patients with uncomplicated hypertension but it blunted or reversed the antihypertensive effect of either diuretic or propranolol therapy. 4. Salt and water retention may be an important factor in the blood pressure-raising effect of indomethacin during diuretic or propranolol therapy: In addition, prostaglandin synthesis may be important in counteracting increased alpha-adrenergic tone, which may limit the blood pressure-lowering effect of beta-adrenoreceptor-blockade. 5. Because of these interactions and their pressor potential indomethacin should be used with caution when combined with either diuretics or beta-adrenoreceptor blockers.
 ...
PMID:Effects of indomethacin alone and during diuretic or beta-adrenoreceptor-blockade therapy on blood pressure and the renin system in essential hypertension. 28 51

The effects of an inhibitor of prostaglandin (PG) synthetase, indomethacin, were studied on renal blood flow (RBF) and mean aortic blood pressure (MABP) and related to changes in concentrations of PGs in renal venous blood under widely different experimental conditions. Although levels of PGE-like material ("PGE") in renal venous blood of the chloralose-anesthetized-laparotomized dog were 8-fold greater than in conscious dogs, viz., 0.39 vs. 0.05 ng/ml of blood, respectively, RBF and MABP were similar for each group. Indomethacin in doses as high as 10 mg/kg, iv, affected neither RBF, MABP, nor PG levels either in the conscious dog or in the anesthetized dog. However, in the anesthetized-laparotomized dog, smaller doses of indomethacin (2 mg/kg, iv) decreased RBF by more than 40% and increased MABP by 15%. This was associated with a decline in concentration of renal venous PGs to those levels observed in conscious dogs. The principal renal PG varied according to the experimental conditions. The venous levels of "PGF" were greater than "PGE" in conscious dogs, whereas in acutely stressed dogs the renal venous concentrations of "PGE" were more than 2-fold those of "PGF". Plasma renin activity was highly correlated with "PGE" levels in renal venous blood, but not with "PGF" levels. Thus, in the acutely stressed dog, the renal circulation is supported by a major PG component, withdrawal of which results in a decline in RBF. In contrast, in the conscious dog at rest, renal PGs do not appear to contribute significantly to RBF. The significance of the small basal release of PGs into the renal venous effluent of the conscious dog, which is not affected by indomethacin, remains to be determined.
 ...
PMID:Contribution of prostaglandins to the renal circulation in conscious, anesthetized, and laparotomized dogs. 40 93

Urinary excretion of immunoreactive prostaglandin E (iPGE) was measurably increased in five of seven patients with Bartter's syndrome. The effects of indomethacin were compared with those of either aspirin or ibuprofen in four patients. Indomethacin produced notably greater suppression of urinary iPGE, greater sodium and potassium retention, greater increases in serum potassium, and decreases in plasma renin activity and in creatinine clearance than the other inhibitors. This demonstration that there is a close correlation between the suppression of urinary iPGE excretion and the extent of correction of the clinical abnormalities in Bartter's syndrome, regardless of the chemical structure of the prostaglandin synthetase inhibitor, is further evidence for the importance of prostaglandins in the pathogenesis of this syndrome.
 ...
PMID:Prostaglandin synthetase inhibitors in Bartter's syndrome. Effect on immunoreactive prostaglandin E excretion. 41 83

Prostaglandins are thought to play an important role in the local regulation of glomerular blood flow and in the release of renin from the juxtaglomerular apparatus. We therefore examined prostaglandin synthesis by isolated rat glomeruli. Isolated glomeruli were either prelabeled with [14C] arachidonic acid or were incubated with [14C] arachidonic acid for the entire experimental incubation in Krebs buffer. Prostaglandin synthesis was determined by thin layer radio-chromatography of acid extracts of the supernatant solutions. Indomethacin inhibitable synthesis of small amounts of 6-keto-PGF1 alpha, the metabolite of prostacyclin (PGI2,) and larger amounts of PGF2 alpha, and PGE2, and possibly thromboxane B2 (TXB2) by isolated glomeruli could be demonstrated with either prelabeling or direct incubation. These findings support the hypothesis that prostaglandins are produced within the glomerulus where they may affect local glomerular blood flow and function.
 ...
PMID:Prostaglandin synthesis in isolated glomeruli. 44 27

The response to indomethacin of a patient with Bartter's syndrome and proximal tubular sodium wasting is described. The patient had evidence of excessive prostaglandin activity (elevated urinary prostaglandin E metabolite [PGE-M] excretion) which returned to normal with indomethacin therapy. Indomethacin administration corrected the defect in proximal tubular sodium resorption, but suppressed plasma renin activity and urinary aldosterone excretion only when sufficient dietary sodium was available to allow for extracellular fluid volume (ECFV) expansion. We conclude that the proximal tubular defect in sodium resorption may have been caused by excessive prostaglandin activity and that the sustained hyperactivity of the renin-aldosterone system was mediated by ECFV depletion.
 ...
PMID:Analysis of factors influencing the renin-aldosterone system in a patient with Bartter's syndrome. 45 81


1 2 3 4 5 6 7 8 9 10 Next >>