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

Converting enzyme inhibition of the renin-angiotensin system has proved a valuable therapeutic approach in patients with severe chronic congestive heart failure. In the present study, a new long-acting converting enzyme inhibitor (enalapril) was evaluated with acute single dose testing (10, 20 or 40 mg) in nine patients with severe chronic congestive heart failure. Four hours after administration, there was a significant reduction of systemic vascular resistance (-19%) and pulmonary wedge pressure (-19%); in addition, there were related increases of cardiac index (+16%) and stroke index (+19%) (probability [p] less than or equal to 0.05 for all changes). This was associated with an increase of plasma renin activity (9 +/- 3 to 35 +/- 11 ng/ml per hour) and a decrease of plasma aldosterone (19 +/- 4 to 9 +/- 2 ng/100 ml) (p less than 0.02 for both). With long-term therapy (1 month), there was improvement of exercise tolerance time and lessening of symptoms based on the New York Heart Association classification. Hemodynamic improvement was maintained in most, but not all, patients. There was no orthostatic hypotension during head-up tilt and hemodynamic values in the upright position were associated with normalization of intracardiac pressures. Long-term converting enzyme inhibition was indicated by a persistent increase of plasma renin activity (16 +/- 2 ng/ml per hour) and a decrease of plasma aldosterone (8 +/- 3 ng/100 ml). In addition, relative angiotensin II receptor occupancy was decreased as judged by the pharmacodynamic response to infusion of the angiotensin II analog saralasin. In conclusion, the long-acting converting enzyme inhibitor, enalapril, was effective in patients with chronic congestive heart failure; however, additional studies will be necessary to further delineate the optimal dose range and identify those patients who are most likely to respond to the drug.
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PMID:Evaluation of a long-acting converting enzyme inhibitor (enalapril) for the treatment of chronic congestive heart failure. 618 89

The renin-angiotensin system has been shown to participate in the pathophysiology of chronic heart failure in many patients. However, the immediate assessment of this contribution in individual patients may sometimes be difficult. As a pharmacologic estimate of angiotensin II receptor activity, we infused the angiotensin II analogue, saralasin, in 20 patients with severe chronic congestive heart failure (CHF). The infusion resulted in blood pressure responses ranging from an agonist pressor response (increased systemic resistance) in patients with low intrinsic renin-angiotensin system activity, to an antagonist depressor response (decreased systemic resistance) in patients with marked activation of the renin-angiotensin system. The ability of the saralasin response to pharmacologically estimate angiotensin II receptor activity in CHF was further revealed by two physiologic maneuvers that decrease endogenous circulating angiotensin II and angiotensin II receptor occupancy. Both converting enzyme inhibition with captopril and sodium repletion, factors known to decrease endogenous angiotensin II activity, provoked agonist responses to saralasin infusion. Furthermore, saralasin was able to reverse the orthostatic hypotension precipitated by converting enzyme inhibition of angiotensin-dependent vascular tone. In summary, saralasin provided a means to estimate angiotensin receptor activity and may therefore serve as a probe of angiotensin-mediated vasoconstriction in the pathophysiology of chronic CHF.
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PMID:Estimation of angiotensin II receptor activity in chronic congestive heart failure. 632 65

Density and affinity of glomerular angiotensin II (ANG II) receptors were determined in normal, untreated, and insulin-treated streptozotocin-diabetic rats 3-4 wk after the onset of diabetes mellitus. With low, intermediate, and high salt intake, angiotensin II receptor density varied inversely with the plasma renin concentration (PRC) in normal, insulin-treated, and untreated diabetic rats. PRC values with all three dietary regimens were lower in the untreated diabetic rats when compared with the other groups. Despite lower plasma renin concentration, however, untreated diabetic rats were also found to have significantly lower glomerular ANG II receptor concentrations at all levels of salt intake. On a normal salt intake, glomerular ANG II receptor density was reduced significantly in untreated diabetic rats (853 +/- 74 (SE) fmol/mg protein), compared with insulin-treated diabetic rats (1,185 +/- 118 fmol/mg) and normal controls (1,058 +/- 83 fmol/mg). ANG II receptor affinity did not change with alternations in salt intake or degree of diabetic control. Reduced glomerular ANG II receptor density in the presence of a suppressed renin-ANG II axis may underlie the altered renal vascular responsiveness to ANG II known to occur in diabetes mellitus.
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PMID:Reduced glomerular angiotensin II receptor density in early untreated diabetes mellitus in the rat. 633 Nov 95

Potassium depletion causes hypotension in normotensive animals and can lower the blood pressure in hypertensive animals and humans. Potential mechanisms for this hypotensive effect include a decrease in aldosterone levels, a decrease in vasopressin, and decreased responsiveness to the pressor effects of angiotensin II. The decreased response to angiotensin II could result from increased prostaglandin production, receptor occupancy, or a decrease in angiotensin II receptor affinity. A high potassium intake has no effect on blood pressure in normotensive animals and humans, but lowers blood pressure in those with hypertension. Mechanisms for this antihypertensive effect include natriuresis with sodium depletion, a decrease in plasma renin activity, an alteration in the neurogenic components of blood pressure regulation, and effects on resistance vessels related either to a high potassium concentration or to a decrease in the number of angiotensin II receptors.
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PMID:Effects of potassium on blood pressure control. 634 96

The hemodynamic consequences of the hypoxic inhibition of angiotensin-converting enzyme activity were studied in chronically instrumented unanesthetized sheep (n = 8) breathing a hypoxic gas mixture for 60 min (PaO2 = 31 mm Hg) followed by reoxygenation with room air. Changes in cardiac output, vascular pressures, blood flow distribution, arterial pH, PaCO2, PaO2, and arterial levels of plasma renin activity, angiotensin II, bradykinin, and catecholamines were measured at selected time points. Seven additional sheep underwent the same protocol but received saralasin, an angiotensin II receptor blocker beginning at 55 min of hypoxia and extending into the reoxygenation period. During hypoxia, both groups developed identical hemodynamic patterns including a rise in cardiac output (25%), blood pressure (15%), and preferential blood flow distribution to the heart, brain, adrenals, diaphragm, and skeletal muscle, as well as a decrease in the fraction of cardiac output to the kidneys and most of the gut. This was associated with a decrease in angiotensin II concentrations (from 35 to 17 pg/ml) in spite of a doubling in plasma renin activity and catecholamines. Bradykinin levels did not change. Upon reoxygenation, bolus production of angiotensin II (from 17 to 1,819 pg/ml) occurred in spite of a constant level of plasma renin activity. Concurrently, different hemodynamic patterns between control and saralasin groups emerged upon reoxygenation, including an elevation from base line in blood pressure and systemic vascular resistance in the control group. Cardiac work (heart-rate systolic pressure product) in the control group remained elevated upon reoxygenation while coronary blood flow returned to base-line values. Saralasin reduced cardiac work upon reoxygenation and restored the match between coronary blood flow and work. We conclude that plasma renin activity and oxygen tension together govern angiotensin II levels for an optimal level of systemic vasomotor tone during hypoxia. However, upon reoxygenation, bolus production of angiotensin II may result in pathophysiologic circulatory patterns, such as impairment in oxygen delivery to the myocardium proportional to persistently elevated cardiac work in the immediate postresuscitation period.
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PMID:Systemic circulatory adjustments to acute hypoxia and reoxygenation in unanesthetized sheep. Role of renin, angiotensin II, and catecholamine interactions. 391 87

The effects of angiotensin II receptor blockade with saralasin ((sar1) (ala8) angiotensin II) have been studied 1-3 days post partum in seven ewes with indwelling vascular cannulae. Control experiments were performed 48 h later in five of the same ewes. The infusion of saralasin at 1, 2, 4 and 8 micrograms kg-1 min-1 resulted in an initial small pressor response, followed by a depressor effect. A significant inverse correlation was demonstrated between log10 dose saralasin and the evoked change in diastolic blood pressure (r = -0.5891, P less than 0.005). A small and inconsistent depressor effect was found in the control experiments; there was no evidence for an association between dose and response (r = +0.0411, P greater than 0.85). These data were compared with those from a previously published study in which an identical infusion protocol for saralasin was used in ten chronically cannulated pregnant ewes. The slopes of the two dose-response curves were very similar (-14.9 +/- 4.3 post partum compared with -14.2 +/- 4.2) in the two groups. However, the average response was greater in the pregnant group, by 7.6 +/- 1.2 mmHg (P less than 0.005). Plasma renin concentration rose significantly during saralasin infusion (P less than 0.05) but was unchanged in control experiments, indicating blockade of the renin-angiotensin system by the removal of negative feed-back control by angiotensin II. Saralasin is known to exert an agonist effect when angiotensin II itself is not directly concerned in the regulation of arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of saralasin in the chronically cannulated ewe in the early puerperium. 636 86

The pressor actions of homologous kidney extract and human angiotensins I and II were studied in the conscious rat snake, Ptyas korros. A converting enzyme inhibitor (captopril), an angiotensin II analogue [( Sar1,Ala8]ANG II), an alpha-adrenergic receptor antagonist (phentolamine), and a catecholamine releaser (reserpine) were used to elucidate their actions. It was found that captopril attenuated the pressor effects of the kidney extract and angiotensin I but not that of angiotensin II. [Sar1,Ala8]ANG II and phentolamine both significantly attenuated, but did not completely inhibit the vasopressor actions of the kidney extract and angiotensins I and II. However, reserpine administration did not reduce the action of angiotensin II. These findings suggest that the renin-angiotensin system in snakes is similar to those present in mammals and other nonmammalian species, except for the mechanism of angiotensin II action. In the present study, angiotensin II was found to act partly through the alpha-adrenergic receptor which is not as specific as that in mammals and thus may respond to an agonist other than its usual ones, and partly through the vascular angiotensin II receptor.
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PMID:The vasopressor action of the renin-angiotensin system in the rat snake, Ptyas korros. 639 11

Mouse brain renin and kidney renin were purified by a 3-step procedure: acetone powder extraction. Sephadex G-100 chromatography, and blue agarose affinity chromatography. The latter efficiently separated from cathepsin D-like acid protease activity. Mouse brain renin had an optimum of enzyme activity of pH 7.0. This differed from mouse kidney renin, which had an optimum at pH 8.5. In vitro, brain renin formed angiotensin I from rat plasma angiotensinogen and had no angiotensinase activity. Mouse brain renin was inhibited by monospecific antibodies raised against pure mouse submandibular gland renin. In vivo activity of the enzyme was tested by injection of brain renin into the lateral brain ventricle of rats. This resulted in the formation of angiotensin I from endogenous brain angiotensinogen, in the stimulation of water uptake, and in a long-lasting increase of arterial blood pressure. The latter could be blocked by the competitive angiotensin II receptor antagonist, saralasin. The results showed that brain renin is active under physiological conditions.
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PMID:In vivo activity of purified mouse brain renin. 702 Aug 79

The renin-angiotensin system plays an important role in blood pressure homeostasis, but the contribution of the type 2 angiotensin II receptor (AT2R) is still unclear. The reports that the AT2R gene has been mapped to the X chromosome in human and rat and the previous report of a gene, Bp3, on the X chromosome responsible for an increase in blood pressure have suggested that the rat AT2R gene (Agtr2) could be this gene. To elucidate whether Agtr2 is Bp3, Agtr2 was cloned. A simple sequence repeat in the 3'-flanking region of this gene was identified and used as a genetic marker to map Agtr2 to the X chromosome at 18.1 cM distal to the androgen receptor locus. This map position is outside the confidence interval reported for Bp3, demonstrating that Agtr2 cannot be Bp3. However, these data will enhance the research into the AT2R biology as well as the study of the X chromosome.
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PMID:Cloning, characterization, and genetic mapping of the rat type 2 angiotensin II receptor gene. 749 Jan 61

Activation of the renin-angiotensin system by sodium deficiency is associated with reciprocal changes in the expression of angiotensin II receptors in adrenal glomerulosa and vascular smooth muscle cells. The effects of dietary sodium changes on the expression of brain angiotensin receptor subtype 1 (AT1) mRNAs were examined in rats maintained on normal, low, and high sodium intake for 3 weeks. Plasma aldosterone and renin activity were elevated in rats maintained on a low salt diet compared with normal rats and were reduced in rats maintained on a high salt diet. These results are consistent with previous findings on the effects of altered dietary sodium on the renin-angiotensin system. The expression of AT1A and AT1B receptor subtype mRNAs was determined by quantitative reverse transcriptase-polymerase chain reaction during changes in sodium intake. The results revealed that sodium deprivation enhanced the expression of AT1B receptors in decorticated brains by 164% compared with high sodium intake. Conversely, high sodium diet increased the expression of AT1A receptors by 155% in the brain compared with low sodium intake. These data suggest that AT1A and AT1B receptors play reciprocal roles in central mechanisms for the control of fluid homeostasis. Further analysis of the molecular biology of angiotensin II receptor regulation in the brain may provide new insights into the interplay between the renin-angiotensin system and blood pressure regulation and also into the role of angiotensin II in the pathogenesis of essential hypertension.
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PMID:Regulation of angiotensin II receptors in rat brain during dietary sodium changes. 750 98


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