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)

Studies were undertaken to compare and evaluate the influence of angiotensin II and its heptapeptide fragments, des-Asp-1-angiotensin II, at various receptor sites for angiotensin in both dogs and rats. Receptor sites evaluated were those which are found in the glomerulosa, reticularis, and fasiculata of the adrenal cortex, in the renal arterioles and the juxtaglomerular cells of the kidney, and in the peripheral arterioles. Both peptides produced similar changes in the steriod secretion profiles for aldosterones, corticosterone, and cortisol in the dog. In the rat, both peptides similarly increased aldosterone and corticosterone secretion; however, a larger dose of the competitive antagonist Sar-1,Ala-8-angiotensin II was required to block the steroid response to the heptapeptide. This finding suggests that receptor affinity for des-Asp-1-angiotensin II may be greater than its affinity for angiotensin II. Both peptides also decreased renin secretion and renal blood flow similarly in the dog. The pressor response to the heptapeptide was only about one-half the pressor response to angiotensin II in both the rat and dog studies. Collectively, these observations in dogs and rats suggest that des-Asp-1-angiotensin II may mediate the response to the renin-angiotensin system at both adrenal and renal receptors.
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PMID:Evidence that des-Asp1 angiotensin II mediates the renin-angiotensin response. 17 68

This study was designed to ascertain whether renal vascular angiotensin receptors differ from other systemic angiotensin receptors and whether, on that basis, antagonists with greater specificity for the renal vasculature can be defined. Femoral and renal blood flow and their responses to angiotensin II (AII) and its heptapeptide analogue, 1-des Asp AII (AIII), were measured with an electromagnetic flowmeter in 26 dogs. For the kidney, the threshold doses of AII and AIII were identical (2.5+/-0.27 vs. 2.3+/-0.35 pmol/100 ml renal blood flow, with similar dose-response curves. In contrast, AII had a greater pressor effect (P less than 0.001) and produced more femoral vasoconstriction (P less than 0.001) than AIII. All four antagonists studied (1-Sar, 8-Ala AII [P113]; 8-Ala AII; 1-des Asp, 8-Ala AII; 1-des Asp, 8-Ile AII) induced parallel shifts in the renal blood flow response to AII and AIII. P113 induced greater blockade than 8-Ala AII (P less than 0.001) which, in turn, was more effective than 1-des Asp, 8-Ala AII (P less than 0.001). 1-des Asp, 8-Ile AII was as effective as P113. Each analogue induced an identical inhibition of the renal vascular response to AII and AIII. In addition, AII and AIII induced cross-tachyphylaxis. All lines of evidence suggested that AII and AIII act on a single receptor in the kidney, which differs at least functionally from other systemic vascular receptors. The possibility that heptapeptide analogues represent angiotensin antagonists with greater specificity for the renal vasculature was pursued in a model in which the renin-angiotensin system is activated. Acute, partial thoracic inferior vena caval occlusion was induced in an additional 16 dogs. P113 induced progressive, dose-related hypotension and a limited increase in renal blood flow in this model. The 1-des Asp, 8-Ile AII analogue, conversely, induced a consistent, larger, dose-related renal blood flow increase, with significantly less hypotension over a wide dose range. We conclude that the renal vascular receptor differs sufficiently from systemic angiotensin receptors that heptapeptide analogues of AII will be useful in exploring angiotensin's role in states characterized by disordered renal perfusion and function.
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PMID:Angiotensin antagonists with increased specificity for the renal vasculature. 19 Feb 70

Adrenal steroid secretion rates and the renin-angiotensin-aldosterone (RAA) system were studied in the normothermic marmot. Adrenal secretion by the anesthetized, laparotomized marmot was (mean +/- SEM); aldosterone 1.2 +/- 0.3 ng/min, deoxycorticosterone 16.7 +/- 11.5 ng/min, corticosterone 15.2 +/- 7.8 ng/min, and cortisol 554 +/- 108 ng/min. Four forcings were investigated that affect feedback control at different sites: adrenocorticotropic hormone (ACTH) and angiotensin II (AII) infusion, sodium (Na) depletion, and Na loading. Plasma aldosterone, cortisol, Na, and potassium (K) concentrations as well as plasma renin activity (PRA) hematocrit (Hct), and in some studies, blood pressure were measured. ACTH infusion increased the plasma concentrations of aldosterone and cortisol. AII infusion increased aldosterone concentration, blood pressure, and Hct. Na depletion increased aldosterone, Hct, and PRA; plasma Na and K were decreased. Aldosterone concentration, Hct, and PRA decreased after salt loading. Normothermic, salt-depleted marmots demonstrated a pronounced fall in blood pressure following infusion of the AII analog, 1-sarcosine-8-alanine AII. The average plasma values for aldosterone, PRA, and cortisol found in 44 control animals were: aldosterone 3.8 +/- 0.3 ng/100 ml, PRA 1.9 +/- 0.2 ng AI-ml-1-h-1, and cortisol 54 +/- 4 ng/ml. It was concluded that normothermic marmots have a RAA system comparable to other mammalian species.
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PMID:Renin-angiotensin-aldosterone system of the normothermic marmot. 19 79

Previous studies have suggested that angiotensin II and sodium can act as alternative mechanisms in maintaining high blood pressure in chronic renovascular hypertension, In the present study, exchangeable sodium was measured in rats in which angiotensin II has been confirmed or excluded as the main cause of the hypertension. To determine the degree of participation of angiotensin II in the maintenance of the high blood pressure, we studied the mean blood pressure response to an angiotensin antagonist (1-Sar-8-Ala-angiotensin II) and to a converting enzyme inhibitor (SQ20,881). Rats with a decrease in blood pressure of less than 20 mm Hg, in response to both inhibitors, were classified as nonresponders; those with a decrease of 20 mm Hg or more, as responders. Fifty percent of the rats with two-kidney hypertension were nonresponders, and they had lower blood pressure and plasma renin activity than the responders. Further, these two-kidney, hypertensive, nonresponder rats had normal exchangeable sodium. The two-kidney hypertensive responders, on the other hand, had significantly higher exchangeable sodium than both the two-kidney, hypertensive nonresponders and the two-kidney control rats. These results suggest that angiotensin II and exchangeable sodium do not play a major role in the maintenance of the high blood pressure in the two-kidney hypertensive nonresponders. However, there appears to be an abnormal relationship between renin and exchangeable sodium in the two-kidney hypertensive responders that could contribute to the maintenance of the hypertension.
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PMID:Exchangeable sodium in angiotensinogenic and nonangiotensinogenic renovascular hypertension. 23 88

The evolution of malignant hypertension was studied under metabolic balance conditions in 11 uninephrectomized rats given deoxycorticosterone acetate and 1% NaCl as drinking water. Changes in sodium and potassium balance were related to changes in blood pressure, plasma renin activity, hematocrit, and kidney histology. After 3-4 weeks of steadily positive sodium balance accompanied by continuously increasing blood pressure up to 185 plus or minus 19 (SE) mm Hg, periods of sodium loss accompanied by evidence of hemoconcentration were observed marking the onset of the malignant phase as defined by the development of fibrinoid necrosis in the kidney. Plasma renin activity remained markedly suppressed both at the fourth week (0.33 plus or minus 0.02 ng/ml hour-1) when the sodium balance was positive and the kidney biopsy negative and at the end of the experiment (0.35 plus or minus 0.36 ng/ml hour-1) when the sodium balance was negative and the kidney histology revealed malignant vasculitis. Infusion of the angiotensin II inhibitor 1-Sar-8-Ala-angiotensin II consistently failed to affect blood pressure, and the kidney tissue norepinephrine level was reduced (0.054 plus or minus 0.01 mug/g) compared with the control level (0.132 plus or minus 0.02 mug/g). We conclude that malignant vasculitis in this model is preceded by hypertension associated with sodium and water retention and is accompanied by negative sodium balance, decreases in body weight, falling blood pressure, and hemoconcentration without demonstrable participation of the renin-angiotensin system or the renal catecholamines.
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PMID:Malignant hypertension resulting from deoxycorticosterone acetate and salt excess: role of renin and sodium in vascular changes. 23 7

Vasodilating antihypertensive drugs induce hypotension with reflex tachycardia, renin release, and fluid and electrolyte retention. Propranolol can impair this renin release. The studies described here were designed to determine the hemodynamic role of vasodilatory drug-induced renin release and inhibition thereof by propranolol in two animals models, the unanesthetized, normotensive and the unanesthetized, genetically hypertensive rat. In studies with normotensive rats, propranolol impaired renin release and tachycardia resulting from hydralazine and minoxidil and potentiated their hypotensive action. Two additional interventions against the renin-angiotensin system were used in evaluating the mechanism of this potentiation. One was removal of the renin source by nephrectomy, and the second was blockade of angiotensin's vasoconstrictor action using a selective angiotensin antagonist, saralasin (1-Sar-8-Ala-angiotensin II (previously known as P113)).. Both interventions potentiated vasocilatory drug hypotension, as did propranolol, but did not prevent reflex tachycardia. When combined with saralasin propranolol did not add to protentiation by this peptide. A similar pattern of blood pressure decrement and potentiation was seen in genetically hypertensive rats when propranolol or saralasin treatment preceded hydralazine. Propranolol was demonstrated to block hydralazine-induced increases in serum renin activity in genetically hypertensive rats. We conclude that hypotensive potentiation of vasocilating drugs by propranolol in these animal models is mediated to a large extent by impairment of renin release. Persistence of hypotensive tachycardia after nephrectomy and after saralasin in normotensive rats suggests the irrelevance of angiotensin's central nervous system stimulation to this cardiac effect. Clinical studies are underway to quantify the potential importance of this beneficial drug interaction in man.
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PMID:Altered renin release and propranolol potentiation of vasodilatory drug hypotension. 23 25

The development of malignant hypertension was studied in stroke-prone spontaneously hypertensive rats (SHR) kept on 1% NaCl as drinking water. Along with salt-loading, blood pressure gradually increased and reached a severe hypertensive level (greater than 230 mmHg), which was followed by increases in urinary protein (greater than 100 (mg/250 g body wt)/day) and plasma renin concentration (PRC, from 18.9 +/- 0.1 to 51.2 +/- 19.4 (ng/ml)/h, mean +/- SD). At this stage, renal small arteries and arterioles showed severe sclerosis and fibrinoid necrosis. Stroke was observed within a week after the onset of these renal abnormalities. The dose of exogenous angiotensin II (AII) producing 30 mmHg rise in blood pressure increased with the elevation of PRC, from 22 +/- 12 to 75 +/- 36 ng/kg, which was comparable to that in rats on water. The fall of blood pressure due to an AII inhibitor, [1-sarcosine, 8-alanine]AII (10(microgram/kg)/min for 40 min) became more prominent with the increase in PRC in salt-loaded rats, but was not detected in rats on water. These findings suggest that the activation of renin-angiotensin system participates in malignant hypertension of salt-loaded stroke-prone SHR rats that show stroke signs, proteinuria, hyperreninemia, and renovascular changes.
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PMID:Renin-angiotensin system in stroke-prone spontaneously hypertensive rats. 42 75

The effect of furosemide on plasma renin, vasopressin (AVP), and aldosterone concentrations was studied in 10 control and 6 nephrectomized lambs during the 1st 2 wk of life. In a separate study in 10 newborn lambs, 1-sarcosine-8-alanine-angiotensin II (saralasin acetate, 5 mug/kg per min) was infused alone for 40 min, after which furosemide 2 mg/kg i.v. was injected in association with continuing saralasin acetate infusion. Plasma renin activity increased from a mean (+/-SEM) of 21.3+/-3.4 ng/ml per h in the 10 control lambs to 39.4+/-8.2 ng/ml per h at 8 min (P < 0.001) and remained high through 120 min after furosemide. Plasma AVP and aldosterone concentrations increased from respective mean values of 2.1+/-0.4 muU/ml and 12.8+/-2.5 ng/dl to 9.8+/-2.0 muU/ml (P < 0.01) and 23.0+/-7.7 ng/dl (P < 0.05) at 35 min and 13.8+/-2.1 muU/ml and 23.0+/-4.4 ng/dl at 65 min after furosemide (each P < 0.01). There was an insignificant AVP response in the 10 lambs treated with angiotensin inhibitor: from a mean base line of 4.7+/-0.9 to 8.3+/-2.0 muU/ml at 35 min, and 7.4+/-2.0 muU/ml at 65 min after furosemide. There was no increase in AVP in the anephric lambs. The mean increment AVP response from base line in the newborn lambs without saralasin, Delta 10.8+/-2.0 muU/ml, was greater than in the lambs with saralasin, Delta4.0+/-1.9 (P < 0.05), and greater than in the anephric lambs, Delta3.3+/-2.1 muU/ml (P < 0.05). The mean blood pressure fell 6 mm Hg in the 10 control lambs (P < 0.05), 7 mm Hg in the anephric lambs (P < 0.05), and 16 mm Hg in the lambs treated with angiotensin inhibitor (P < 0.05) by 35 min after furosemide. However, the changes in plasma AVP were not related to the fall in blood pressure. These data support the view that the observed AVP response to furosemide in the newborn lamb was mediated through the renin-angiotensin system.
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PMID:Endogenous angiotensin stimulation of vasopressin in the newborn lamb. 42 54

In obese females, 50 g of alanine given orally on the fifth day of fasting, produced a decrease in urinary sodium that persisted the following day. Plasma renin did not increase the day following alanine intake.
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PMID:Sodium sparing effect of alanine in fasting obese females. 46 1

The mechanisms involved in residual or recurrent hypertension following operation to correct renal artery stenosis were studied in 10 patients by performing angiotensin II blockade with Saralasin (Sarcosine, alanine, angiotensin II) before and after operation. Peripheral renin and renal vein renin determinations, angiography, and renography were done as well. The limitations of renin determinations are cited and the application of angiotensin II blockade as a specific method of detecting renin-dependent hypertension before and after operation are presented. Saralasin infusion under the controlled conditions of our study proved to be a sensitive method for detection of renin-dependent hypertension. The results of Saralasin infusion correlated closely with peripheral and renal vein renin determinations. Thus angiotensin II blockade before and after operation may supercede more invasive and less specific diagnostic methods.
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PMID:Evaluation of surgical response in renovascular hypertension using angiotensin II blockade. 71 82


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