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)

Adrenocortical function was assessed in six normal and six chronic (greater than 12 weeks), DOCA-hypertensive Yucatan miniature swine; mean arterial pressures were 115.3 +/- 11.7 and 163.6 +/- 27.2 mm Hg, respectively (mean +/- SEM). Adrenocortical function was evaluated in vivo by measuring changes in plasma cortisol and aldosterone in response to exogenous ACTH (0.25 mg, iv), and in vitro by measuring the responses of collagenase-isolated adrenocortical cells to ACTH and angiotensin II. Corticoids were measured by specific radioimmunoassay. Basal plasma cortisol values of conscious DOCA-hypertensive swine were approximately 53% of the values of normotensive swine (P less than 0.05). However, ACTH induced a 419% increase in plasma cortisol values in DOCA-hypertensive swine compared to a 261% increase in the normotensive swine (P less than 0.05). These differences between the two groups were not altered by anesthesia. There were no significant differences in ACTH-induced changes in plasma aldosterone between the normotensive and DOCA-hypertensive swine. Experiments in vitro showed that the corticoid secretory responses of adrenocortical cells from DOCA-hypertensive animals were 6 times more sensitive to ACTH and 3.2 times more sensitive to angiotensin II than those of cells from normotensive swine. Thus, despite the possibility of adrenocortical insufficiency due to suppressed plasma renin activity and the negative feedback of DOCA on the hypothalamic-hypophyseal-adrenal axis, adrenocortical function of DOCA-hypertensive swine was hyperresponsive to trophic hormones. Results from this study suggest that the DOCA-hypertensive swine may be a valuable model in elucidating the relationship between hypertension and adrenocortical function and in investigating nonclassical control of the adrenal cortex, that is, control exerted during the hypertensive state that exists apart from or in addition to that exerted by ACTH and angiotensin II.
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PMID:Adrenocortical function in deoxycorticosterone acetate (DOCA)-hypertensive Yucatan miniature swine. 298 91

Antihypertensive activity of alacepril (1-[(S)-3-acetylthio-2-methylpropanoyl]-L-prolyl-L-phenylalanine, DU-1219), an orally active angiotensin converting enzyme (ACE) inhibitor, was investigated in hypertensive models with normal or low plasma renin activity (PRA). After single oral administration in spontaneously hypertensive rats (SHR), alacepril (1-30 mg/kg) showed a dose related antihypertensive effect with a gradual onset and long lasting action. The maximum hypotensive effect was about 3 times more potent than that of captopril (3-100 mg/kg) on a weight basis. When comparing the AOC (area over the antihypertensive curve) values, the overall antihypertensive activity of alacepril was 8 times stronger than that of captopril. In deoxycorticosterone acetate-salt (DOCA-salt) hypertensive rats, alacepril (10-100 mg/kg) produced a significant and sustained hypotensive effect. The maximum hypotensive potency and the overall antihypertensive activity of alacepril were remarkably stronger than those of captopril (30, 100 mg/kg). During once daily successive oral administration for 10 days in SHR, alacepril (3-10 mg/kg/d) reduced dose relatedly the daily starting blood pressure. In DOCA-salt hypertensive rats and dogs, alacepril (30 mg/kg/d) produced a significant antihypertensive effect, while captopril (30 mg/kg/d) did not reduce daily starting blood pressure. Therefore, it may be expected that alacepril is a more effective antihypertensive agent than captopril in various hypertensions of different etiology.
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PMID:Antihypertensive activity of alacepril in spontaneously hypertensive rats and deoxycorticosterone acetate-salt hypertensive rats and dogs. 300 Mar 90

In the single dose study, the aortic blood pressure in conscious normotensive rats, 2-kidney, 1-clip renal hypertensive rats (2K-RHR), 1-kidney, 1-clip renal hypertensive rats (1K-RHR) or DOCA hypertensive rats was measured for 24 hr after the oral administration of angiotensin converting enzyme (ACE) inhibitors such as MK-421 or captopril. MK-421 at 3 mg/kg and captopril at 10 mg/kg markedly lowered the blood pressure of 2K-RHR. MK-421 at 10 mg/kg and captopril at 30 mg/kg only modestly lowered the blood pressure of 1K-RHR. In contrast, both ACE inhibitors failed to reduce blood pressure in DOCA and normotensive rats. In the repeated dose study, the systolic blood pressures in normotensive rats, 2K-RHR or spontaneously hypertensive rats (SHR) were measured twice a week for 3 weeks treatment of either MK-421 at 3 mg/kg or captopril at 10 mg/kg. Both ACE inhibitors produced significant antihypertensive effects in these model rats, and the effects were sustained throughout the treatment period. The antihypertensive effects in 2K-RHR were greater than those in SHR and normotensive rats. These results indicate that MK-421 and captopril cause the most significant antihypertensive effect in 2K-RHR in which the renin-angiotensin system played a dominant role in blood pressure regulation. The antihypertensive effect of MK-421 was approximately 3 times as potent as that of captopril in these hypertensive models.
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PMID:[Effects of single and repeated oral administration of MK-421 and captopril on blood pressures in normotensive and experimental hypertensive rats]. 300 25

The antihypertensive action of N-[N-[(S)-1-ethoxycarbonyl-3-phenyl-propyl]-L-alanyl]-N-(indan-2-yl) glycine hydrochloride (CV-3317), a nonsulfhydryl compound characterized as an angiotensin converting enzyme inhibitor in our previous work, was examined in hypertensive animal models. In 2-kidney, 1 clip hypertensive rats and dogs, CV-3317 (3 and/or 10 mg/kg, p.o.) produced a sustained antihypertensive action of about 15 to 25 mmHg. Daily oral administrations of CV-3317 (1 to 10 mg/kg/day) to spontaneously hypertensive rats (SHR) for 5 weeks produced a sustained antihypertensive action of 20 to 40 mmHg. When CV-3317 (3 mg/kg) was combined with hydrochlorothiazide (10 mg/kg), its antihypertensive action was intensified in potency and duration. CV-3317 (30 mg/kg) induced a slight hypotension (5 to 10 mmHg) in normotensive rats, but had no effect on the blood pressure of 1-kidney, 1 clip hypertensive rats and on that of a low renin type of DOCA/salt hypertensive rat. The antihypertensive activity of CV-3317 was more potent than that of captopril. In pithed SHR, the pressor response induced by an electrical stimulation of the preganglionic sympathetic nerve, but not the pressor response to norepinephrine, was attenuated by both agents (0.3 mg/kg, i.v.). Both agents may exert their antihypertensive action not only primarily by inhibiting the renin-angiotensin system, but also by inhibiting norepinephrine release from the sympathetic nerve terminals indirectly by reducing the formation of vascular angiotensin II.
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PMID:Antihypertensive action of a non-sulfhydryl angiotensin converting enzyme inhibitor (CV-3317) in various hypertensive models. 302 85

A carboxy terminal renin complementary DNA (cDNA) clone from rat kidney was isolated, characterized, and used as a probe for renin messenger RNA (mRNA) quantification in normotensive and hypertensive rats. RNA blotting analysis detected renin mRNA in control kidney and brain. Deoxycorticosterone acetate (DOCA) and high salt (1%) treatment of experimental animals resulted in a greater than 95% decrease in the content of renin mRNA in the kidney, as compared with values in control rats receiving 0.4% NaCl in their diet. In contrast, high salt (1%) treatment alone caused only a twofold decrease in kidney renin mRNA content, as compared with values in controls. DOCA and low salt (0.04%) or low salt (0.04%) treatment alone caused a 1.5-fold increase in the kidney renin mRNA content, as compared with values in control rats. These results indicate that DOCA and salt have a synergistic effect in depressing renin mRNA levels in kidney. Clipping of the left renal artery caused a threefold increase in the steady state level of renin mRNA in the ischemic kidney and a 0.5-fold decrease in the hypertrophied kidney. The data are consistent with the hypothesis that blood pressure and other stimuli regulate the expression of the renin gene in vivo.
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PMID:Regulation of renin gene expression in hypertensive rats. 304 41

In a series of experiments, age-dependent differences in the development of DOCA-saline hypertension (HPT) were studied in the rat. Immature animals developed--in contrast to the adult ones--a more severe and self-sustaining HPT, associated with a more pronounced retention of fluid and a greater increase of renal collagen which was preceded by a more rapid decrease in renal renin content. It is suggested that changes in intrarenal haemodynamics due to the suppression of renal renin-angiotensin system play a role in the pathogenesis of hypertensive renal lesions which develop more readily in immature animals and are responsible for their more severe HPT. Similarly, monkeys exposed to increased salt intake from earliest stages of postnatal ontogeny are also more prone to develop salt hypertension more rapidly than the adult ones. The increased salt intake before sexual maturity may thus be considered as a risk factor for the development of hypertension also in man.
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PMID:Salt and experimental hypertension: the influence of age. 309 17

The objective of the present study was to investigate the effects of an angiotensin II (AII) analogue, Des-Asp1-AII and of two competitive blockers, [Leu8]-AII and [octanoyl-Leu8]-AII, infused intracerebroventricularly on the ingestion of water and of a 3% NaCl solution, as well as on diuresis and natriuresis in normal rats and in adrenalectomized and deoxycorticosterone (DOCA)-treated rats. Both AII and Des-Asp1-AII increased water and 3% NaCl intake and increased urine and Na+ excretion, the effect of AII being more intense. Except for 3% NaCl, the responses of all other parameters were totally or partially reduced by previous treatment with [Leu8]-AII or [octanoyl-Leu8]-AII. Subcutaneous DOCA injection caused water ingestion. Previous treatment with DOCA increased the response to AII for the ingestion of 3% NaCl and inhibited sodium excretion. The results obtained for adrenalectomized rats treated with DOCA, AII and analogous agonists did not differ from those observed in normal rats. These data suggest a possible synergism between the cerebral and renal renin-angiotensin systems in the regulation of the physiological parameters studied.
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PMID:Effects of intracerebroventricular infusion of angiotensin II and related peptides on water and sodium ingestion and excretion. 322 47

1. Normal rats and passive Heymann membranous glomerulonephritic rats were chronically treated with DOCA/NaCl for 9 weeks. Normal and untreated nephritic rats were used as controls. Urinary kallikrein excretion (UKE), proteinuria and tail blood pressure (BP) were determined in awake rats. Glomerular filtration rate (GFR), plasma renin activity (PRA), and plasma potassium (PK) concentration were measured at the end of the experiment. 2. Comparison between basal and 9th-week measurements indicated that DOCA/NaCl administration significantly increased (P less than 0.05) UKE (3.96 +/- 0.30 vs 7.60 +/- 1.51 U/24 h) and BP (118 +/- 2 vs 135 +/- 6 mmHg) in normal rats, whereas in nephritic DOCA/NaCl-treated rats, UKE was unaltered (3.80 +/- 0.50 vs 3.40 +/- 0.30 U/24 h) and BP increased to higher levels (117 +/- 2 vs 152 +/- 3 mmHg) than in the normal DOCA/NaCl group (P less than 0.05). Passive Heymann nephritis alone did not affect UKE (3.56 +/- 0.40 vs 3.60 +/- 0.80 U/24 h) or BP (124 +/- 2 vs 125 +/- 2 mmHg). 3. At the end of the study, PK was decreased and PRA totally suppressed in both normal and nephritic DOCA/NaCl-treated rats. Proteinuria was more pronounced in nephritic DOCA/NaCl-treated rats (44.8 +/- 5.2 mg/day) than in control nephritic animals (15.1 +/- 2.4 mg/day) and GFR was increased equally in both DOCA/NaCl-treated groups. 4. The failure of nephritic rats to respond to DOCA/NaCl by increasing UKE was not associated with any significant derangement of renal function or structure and may have been related to the aggravation of arterial hypertension in this group.
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PMID:Nephritis blunts urinary kallikrein excretion and aggravates DOCA/NaCl hypertension in rats. 324 40

This study describes the development of an experimental model of reversible acute renal failure following infusion of contrast media radiographic dye. Experiments were also performed to investigate possible methods of prevention as well as examine single nephron mechanisms involved in the pathogenesis of the renal failure. Acute renal failure was consistently produced by indomethacin treatment (18 mg/kg) and an intravenous infusion of contrast media (7 ml/kg) into New Zealand rabbits that had been on a low sodium diet for one week. Glomerular filtration rate (GFR), measured by daily creatinine clearance in unanesthetized animals, was significantly decreased (P less than 0.001) 24, 48, and 72 hours following infusion of the contrast dye. Two weeks after induction of acute renal failure, GFR had returned to control. GFR was unchanged during the same time period when the sodium deprived rabbits were given either indomethacin or contrast media alone. Chronic administration of DOCA (1 mg/kg s.c.) and saline drinking water which increased sodium and solute excretions and decreased plasma renin activity also prevented the decrease in GFR. However, acute infusion of either saline or mannitol, which transiently increased sodium and solute excretions and decreased plasma renin activity, did not protect against the development of acute renal failure. Light microscopy revealed no glomerular or tubular changes and no visible obstruction. Micropuncture experiments were performed on three additional groups of anesthetized rabbits: control, acute renal failure, and recovery. Recovery rabbits were allowed a two week period after renal failure before they were micropunctured.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction, prevention and mechanisms of contrast media-induced acute renal failure. 328 68

Studies were performed to examine the effect of saline loading on uranium-induced acute renal failure (ARF) in rats. Forty-eight hours after the i.v. injection of uranyl acetate (UA, 5 mg/kg), inulin clearance rate (Cin) decreased to approximately 43% of the control value in water drinking rats (P less than 0.005). Animals receiving continuous isotonic saline infusion following UA showed higher urine flow and Cin (60% of control, P less than 0.01), and lessened intratubular cast formation when compared with water-drinking ARF rats. A short-term saline infusion following UA did not attenuate the decline in Cin (43% of control). An inverse relationship was found between Cin and the number of casts (r = -0.75, P less than 0.01). Multiple regression analysis showed that standardized partial regression coefficient is statistically significant between Cin and cast formation (-0.69, P less than 0.05), but not between Cin and tubular necrosis (-0.07, P greater than 0.05). Renin depletion caused by DOCA plus saline drinking did not attenuate the decline in Cin in ARF (47% of control). No significant difference was found in urinary uranium excretion between water-drinking and saline-infused ARF rats. The findings suggest that continuous saline infusion following UA attenuates the decline in Cin in ARF rats; and that this beneficial effect of saline loading is associated with lessened cast formation rather than with suppressed renin-angiotensin activity or enhanced urinary-uranium excretion.
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PMID:The effect of saline loading on uranium-induced acute renal failure in rats. 329 17


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