Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

To elucidate the effect of protein and phosphorus restriction on hemodynamics in chronic renal failure, 14 patients were placed on a low-protein very-low-phosphorus diet (LPVLPD) and observed for metabolic and hemodynamic changes. For three weeks after initiation of the LPVLPD, the patients displayed a positive sodium balance in spite of dietary sodium restriction. During the fourth week, sodium balance decreased and approached zero. Sodium retention was accompanied by a significant decrease in plasma renin activity (P < 0.05) and mean blood pressure (P < 0.01), an increase in body weight (P < 0.05), a slight temporary decrease in hemoglobin (P < 0.05), hematocrit (P < 0.05) and total protein (P < 0.005), a negative nitrogen balance, and an increase in left ventricular ejection fraction (P < 0.01) and peak filling rate (P < 0.05). Serum creatinine concentration and endogenous creatinine clearance did not change during the experiment. These data indicate a role of dietary protein and phosphorus restriction in cardiac and fluid homeostasis in the pathophysiology of chronic renal failure.
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PMID:Effects of dietary protein restriction on hemodynamics in chronic renal failure. 844 Dec 41

The role of the renin-angiotensin system (RAS) in the pathogenesis of cisplatin nephrotoxicity was evaluated in an experimental rat model using a specific, nonpeptide angiotensin II(AII) receptor blocker, losartan. Rats were treated with a single dose of losartan (at 10 mg/kg and 30 mg/kg, i.p.) or saline, 2 h prior to cisplatin administration (5 mg/kg, i.p.). Renal function was assessed 3 and 7 days after cisplatin treatment. A second group of rats received losartan (10 mg/kg, i.p.) or saline, 2 h prior to cisplatin administration (5 mg/kg, i.p.), and losartan (10 mg/kg, i.p.) or saline daily for 6 days after cisplatin treatment. Renal function was assessed on day 7. Neither high- nor low-dose losartan pretreatment prevented development of cisplatin-induced nephrotoxicity. Blood urea nitrogen (BUN) and plasma creatinine values at 7 days were similar to those of animals receiving cisplatin alone (BUN: 17.12 +/- 1.1 and 22.17 +/- 2.2 vs. 20.58 +/- 2.4 mg/dL; creatinine: 1.04 +/- 0.05 and 0.82 +/- 0.09 vs. 0.84 +/- 0.06 mg/dL). A significant reduction in creatinine clearance with cisplatin treatment was seen 3 days after therapy, which was not prevented by pretreatment with losartan (GFR in controls: 2.1 +/- 0.16 mL/min; cisplatin: 0.24 +/- 0.05; cisplatin plus low-dose losartan: 0.05 +/- 0.03 and cisplatin plus high-dose losartan: 0.37 +/- 0.05). All groups of cisplatin-treated rats displayed systemic signs of cisplatin toxicity: reduced food intake and body weight. Rats receiving chronic losartan treatment had more rapid weight gain and lower BUN and plasma creatinine levels on day 7 than rats receiving cisplatin alone (BUN: 24.0 +/- 2.64 vs. 36.4 +/- 0.91 mg/dL; p < 0.05; plasma creatinine: 0.86 +/- 0.06 vs. 1.15 +/- 0.07 mg/dL; p < 0.05). Acute blockade of the AII receptor with losartan does not alter the onset or severity of cisplatin nephrotoxicity. Chronic blockade of the AII receptor may improve the rate of recovery of renal function in cisplatin-treated rats.
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PMID:The role of the renin-angiotensin system in cisplatin nephrotoxicity. 877 Dec 39

It was found in acute experiments on white rats that injection of Salmonella typhimurium lipopolysaccharide activates renin-angiotensin-aldosterone system (RAAS) and causes oligohydruria form of acute renal failure (ARF). Enalapril, angiotensin-converting enzyme, being injected simultaneously with endotoxin, increases diuresis, glomerular filtration rate, electrolytes excretion and reabsorption by proximal tubules, decreases proteinuria and blood nitrogen-down to the normal. Thus, RAAS takes part in endotoxemia ARF induction and enalapril has protective effect.
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PMID:[The participation of the renin-angiotensin-aldosterone system in the pathogenesis of acute kidney failure in endotoxemia]. 881 32

We have studied the integrated neuroendocrine and haemodynamic effects of acute hypoxaemia in ten healthy volunteers studied on two separate occasions. After reaching a resting haemodynamic state, subjects breathed either room air or a nitrogen/oxygen mixture which rendered arterial oxygen saturation between 75% and 80%. Measurements of pulmonary and systemic haemodynamics were made and blood samples taken at baseline and after 30 min breathing air or the hypoxic gas. Blood was assayed for plasma sodium and potassium, renin-angiotensin-aldosterone system activity, natriuretic peptides, cortisol and catecholamines. Hypoxaemia significantly increased heart rate, cardiac output and mean pulmonary artery pressure (Ppa), but not mean arterial pressure compared with normoxaemia. Although plasma renin activity, angiotensin II and cortisol were unaffected by hypoxaemia, plasma aldosterone fell significantly in comparison with normoxaemia. This was associated with an increase in plasma atrial natriuretic peptide (ANP) but not b-type natriuretic peptide (BNP) during hypoxaemia whilst no changes were observed during normoxaemia. The increase in plasma ANP correlated positively with the increase in Ppa. During hypoxaemia there is therefore dissociation of the renin-angiotensin-aldosterone system where plasma aldosterone decreased, despite there being no effects on plasma renin activity and angiotensin II or on plasma cortisol. This dissociation may be due to increased levels of ANP but not BNP having specific inhibitory effects on aldosterone biosynthesis. ANP increased in proportion to the degree of pulmonary vasoconstriction induced by hypoxaemia which may indicate a counter-regulatory role.
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PMID:Acute neurohormonal responses to hypoxaemia in man. 882 Aug 95

The present study enrolled 214 patients, aged 26 to 83 years, with symptomatic New York Heart Association class II through IV congestive heart failure. Patients were continued on their previous therapeutic regimens, which included an angiotensin-converting enzyme (ACE) inhibitor and a loop diuretic with or without digitalis. Patients were randomized to 1 of 5 parallel treatment groups: placebo or spironolactone at a single daily dose of 12.5, 25, 50, or 75 mg for 12 weeks. Serum levels of creatinine, urea nitrogen, potassium, plasma renin activity, and N-terminal proatrial natriuretic factor (pro-ANF), as well as urinary aldosterone levels, were measured periodically. Measurements at 12 weeks versus baseline values indicated significant increases in plasma renin activity and aldosterone excretion and significant decreases in systolic and diastolic blood pressure and pro-ANF. Hypokalemia (serum potassium < 3.4 mmol/L) occurred in 10% of placebo-treated patients and in 0.5% of the spironolactone group. The incidence of hyperkalemia (serum potassium > or = 5.5 mmol/L) was 5% for the placebo group, whereas it was 5%, 13%, 20%, and 24% for the 12.5-, 25-, 50- and 75-mg spironolactone treatment groups, respectively. Predictors of hyperkalemia included the use of ACE inhibitors other than captopril, ACE inhibitor dose, and baseline elevation of serum creatinine or potassium levels. Thus, daily doses of 12.5 to 25 mg of spironolactone coadministered with conventional therapy of ACE inhibitors, loop diuretics, and digitalis are relatively safe (provided that serum potassium levels are monitored) and effective in blocking the effects of aldosterone, while reducing the potential for hypokalemia in patients with heart failure.
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PMID:Effectiveness of spironolactone added to an angiotensin-converting enzyme inhibitor and a loop diuretic for severe chronic congestive heart failure (the Randomized Aldactone Evaluation Study [RALES]). 888 63

A high incidence of maternal toxicity in rabbits characterized by uremia and death was observed when TCV-116, a novel angiotensin II subtype-1 (AT1) receptor antagonist, was orally administered to pregnant rabbits at dosage levels of 3 mg/kg/day or more. The effects of TCV-116 on blood pressure in nonpregnant or male rabbits and rats and on blood chemistry, renal circulation, and plasma renin activity in nonpregnant or male rabbits were examined to characterize the toxicity in rabbits. In a 2-week repeated dose study, most nonpregnant female rabbits receiving 3 or 100 mg/kg/day died or were sacrificed in a moribund state, indicating that toxicity could be caused independently of pregnancy. When these rabbits became moribund, marked hypotension, accompanied by increases in plasma concentrations of urea nitrogen, creatinine, and potassium, was observed, suggesting uremia. In a single-dose study, blood pressure in rabbits was decreased after administration of 10 or 100 mg/kg of TCV-116, and the hypotension was more marked and sustained than that in rats, as was the case with 30 mg/kg of enalapril. The sustained pharmacological effect in rabbits was also confirmed with regard to decreases in effective renal plasma flow and the glomerular filtration rate and increased plasma renin activity. Species differences in the hypotensive effect and mortality could not be explained by toxicokinetic data for the active metabolite of TCV-116 in various species, which supported a possibility that the differences in toxicity may be related to the species difference in sensitivity to the pharmacological effect of TCV-116. We conclude that the specific maternal toxicity of TCV-116 in rabbits may be mainly due to the higher sensitivity of rabbits to the pharmacological effects and is caused by marked and sustained hypotension resulting in the decrease in glomerular filtration rate, uremia, and death.
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PMID:Characterization of the high sensitivity of rabbits to the effects of TCV-116, an angiotensin II receptor antagonist. 902 72

The purpose of this study was to begin to characterize a new inbred strain of adult male hamsters with established spontaneous hypertension along with their genetically/age-matched normotensive controls. We found that mean arterial pressure was 162+/-3 mm Hg in hypertensive hamsters and 94+/-4 mm Hg in controls (mean+/-SEM; P<.05). Body weight was significantly lower in hypertensive hamsters relative to normotensive hamsters (P<.05). Hypertension was associated with a significant increase in heart weight, thickness of the left ventricular wall, and amplitude of the QRS complex in standard electrocardiographic leads I and aVR (P<.05). No gross or microscopic abnormalities were observed in other organs. Plasma renin activity and the number of circulating neutrophils were significantly increased in hypertensive hamsters relative to controls (P<.05). Serum concentrations of creatinine, blood urea nitrogen, sodium, potassium, and calcium as well as urinalysis were similar in both groups. Overall, these data suggest that the spontaneously hypertensive hamster could be a suitable model for the study of spontaneous hypertension.
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PMID:Initial characterization of hamsters with spontaneous hypertension. 926 Sep 96

Iganidipine, a new water-soluble calcium antagonist, was administered at a nonhypotensive dose (NHD) of 0.3 mg/kg/day, a moderate-hypotensive dose (MHD) of 1.0 mg/kg/day, and a sustained-hypotensive dose (SHD) of 3.0 mg/kg/day to Dahl salt-sensitive (Dahl-S) rats fed a high-salt diet for 8 weeks. The effects on survival, and on renal and cerebral injuries, were then examined. Iganidipine completely prevented hypertensive death at the SHD and tended to increase the survival at the NHD and MHD. Iganidipine reduced glomerulosclerosis and renal arterial and tubular injuries in a dose-dependent manner. Iganidipine at the SHD, but not NHD or MHD, improved plasma creatinine, serum urea nitrogen, and glomerular filtration rate. Iganidipine at all doses examined increased the urinary prostaglandin (PG) I2 and PGE2, but not PGF2alpha or thromboxane B2, and decreased plasma angiotensin II (AII) level and renin activity. The renal glomerular, tubular, and arterial injuries were significantly correlated with blood pressure (r = 0.56 to 0.80) and plasma AII level (r = 0.50 to 0.71) but not with urinary prostanoids. Iganidipine also reduced the incidence of cerebral infarction. The infarction area was slightly and significantly correlated with urinary PGI2 (r = 0.42) and PGE2 (r = 0.41) but not with blood pressure or plasma AII. In conclusion, iganidipine prevented renal and cerebral injuries in Dahl-S rats. In addition to the reduced blood pressure, the reduction of plasma AII and the increase of vasodilatory prostanoids may also partially contribute to the renal and cerebral protective effects of iganidipine.
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PMID:Preventive effect of iganidipine on renal and cerebral injuries in salt-induced hypertension. 927 81

Nitric oxide (NO) is a labile radical gas that is widely acclaimed as one of the most important molecules in biology. Through covalent modifications of target proteins and redox reactions with oxygen and superoxide radical and transition metal prosthetic groups, NO plays a critical role in many vital biological processes, including the control of vascular tone, neurotransmission, ventilation, hormone secretion, inflammation, and immunity. Moreover, NO has been shown to influence a host of fundamental cellular functions, such as RNA synthesis, mitochondrial respiration, glycolysis, and iron metabolism. NO is formed from L-arginine by NO synthases (NOSs), a family of related enzymes encoded by separate unlinked genes. The different NOS isozymes exhibit disparate tissue and intrarenal distributions and are governed by unique regulatory mechanisms. In the kidney, NO participates in several vital processes, including the regulation of glomerular and medullary hemodynamics, the tubuloglomerular feedback response, renin release, and the extracellular fluid volume. While NO serves beneficial roles as a messenger and host defense molecule, excessive NO production can be cytotoxic, the result of NO's reaction with reactive oxygen and nitrogen species, leading to peroxynitrite anion formation, protein tyrosine nitration, and hydroxyl radical production. Indeed, NO may contribute to the evolution of several commonly encountered renal diseases, including immune-mediated glomerulonephritis, postischemic renal failure, radiocontrast nephropathy, obstructive nephropathy, and acute and chronic renal allograft rejection. Moreover, impaired NO production has been implicated in the pathogenesis of volume-dependent hypertension. This duality of NO's beneficial and detrimental effects has created extraordinary interest in this molecule and the need for a detailed understanding of NO biosynthesis.
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PMID:Nitric oxide in renal health and disease. 929 59

We investigated the effects of long-term treatment with the angiotensin-converting enzyme inhibitor enalapril and low-salt intake on the survival rate of Dahl salt-sensitive rats fed a high-salt (6.0% NaCl) diet. The systolic blood pressure of the rats increased gradually from 5 weeks of age and reached >240 mm Hg at 12 weeks of age. At this point, a low-salt diet group received a placebo (group 1, n = 10), and the high-salt diet group was divided into three groups: those given a placebo with the high-salt diet (group 2, n = 15), those given a chow change from a high- to a low-salt diet with a placebo (group 3, n = 14) and those given enalapril (30 mg/kg/day p.o., group 4, n = 14). At 19 weeks of age, all rats in group 1 were alive, and the survival rate of group 2 was only 40% (P < .001 vs. group 1). The survival rates of both groups 3 and 4 were significantly better: 86% (P < .01 vs. group 2) and 93% (P < .01), respectively. This beneficial effect on mortality was accompanied by an amelioration of the elevated plasma creatinine and urea nitrogen levels and a decrease in the glomerular sclerosis lesion scores in both groups. These results suggested that a high-salt content diet and the renin-angiotensin system are deterioration factors in lethal renal damage and the limitation of the diet salt content and inhibition of the renin-angiotensin system are important to improve the survival rate in high-salt-loaded hypertensive Dahl salt-sensitive rats.
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PMID:Beneficial effects of long-term enalapril treatment and low-salt intake on survival rate of dahl salt-sensitive rats with established hypertension. 935 78


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