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)

It has been shown that the severity of experimentally induced acute renal failure (ARF) is inversely related to dietary sodium chloride intake, and the effects have been attributed to the concurrent changes in renal renin. In the current study, renal renin of rats was increased by chronic sodium deprivation and decreased by chronic sodium loading and DOCA administration. In two nephrotoxic models (mercuric chloride, uranyl nitrate), giving previously sodium-deprived rats 1% sodium chloride to drink for 48 hours prior to ARF induction greatly attenuated the severity without any reduction in their high renal renin. Conversely, giving previously sodium-loaded rats tap water to drink for 4 to 5 days prior to AFR induction greatly enhanced the severity without any increase in their subnormal renal renin. Therefore, the changes in severity of ARF resulting from changes in dietary sodium are not mediated by changes in renal renin. Significant inverse correlations were found between mean peak BUN values during the follow-up period (5 to 7 days) and the 24-hour urinary sodium excretions prior to ARF induction in both models, suggesting that sodium intake and/or excretion at the time of induction is a good predictor of the severity. The effects of sodium chloride in both models were predominantly expressed during the maintenance phase, and consisted of attenuation of the severity (both models) and hastening of the recovery (mercuric chloride model). Possible mechanisms by which dietary sodium produced its effects, independently of its effects on the renin-angiotensin system, are discussed.
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PMID:Sodium-chloride-induced protection in nephrotoxic acute renal failure: independence from renin. 39 16

The current study was undertaken to examine the effects of dithiothreitol (DDT), a sulfhydryl-reducing agent and heavy metal chelator, on the course of heavy metal-induced acute renal failure in the rat. Groups of rats in metabolic cages received uranyl nitrate (UN) alone, UN plus DTT, mercuric chloride (HgCl2) alone, and HgCl2 plus DTT. UN injected alone produced azotemia, decreased creatinine clearance, and rising fractional sodium excretion over the 48 hr of study. These effects of UN on renal function were not observed when DTT was administered 30 min after UN injection. Qualitatively similar results were obtained with HgCl2-induced acute renal failure. Groups of rats were killed at 6 hr after UN plus DTT, HgCl2 alone, or HgCl2 plus DTT; and determinations of plasma renin activity (PRA) and renin activities of the superficial and deep juxtaglomerular apparatus (JGA) were performed. PRA's and JGA renins were increased in animals receiving either UN or HgCl2 alone, but not in the rats receiving both DTT and UN or HgCl2. The effect of DTT on distribution of 203Hg was also examined. Treatment with DTT did not alter the renal accumulation of 203Hg, suggesting that this agent does not act by limiting renal exposure to the heavy metals. Thus, DTT ameliorates the course of heavy metal-induced ARF, and this effect is associated with prevention of heavy metal-induced alterations in sodium excretion and renin-angiotensin system activity.
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PMID:Effect of dithiothreitol on mercuric chloride- and uranyl nitrate-induced acute renal failure in the rat. 91

It has been previously demonstrated that single neophron filtration rate, whole kidney glomerular filtration rate and total renal blood flow decreased by 30-35% 6 h after uranyl nitrate induced acute renal failure in the rat. In order to evaluate a role of the renin-angiotensin system in the initiating phase (0-6 h) of this model of acute renal failure determinations of plasma renin activity, superficial (S) and deep (D) juxtaglomerular apparatus (JGA) renin activity and distal nephron [Na+] were obtained. Plasma renin activity increased from the control value of 1.5 +/- 0.3 (S.E.M.) to 2.9 +/- 0.4 ng/ml/h (P less than 0.005) at 6 h. Mean renin activity in S- and D-JGA's of control rats was 6.99 +/- 0.41 and 2.67 +/- 0.21 ng/JGA/h, respectively. After uranyl nitrate, renin activity in S-JGA's increased to 13.62 +/- 0.80 ng/JGA/h (P less than 0.001) at 2 h and remained elevated, 12.56 +/- 0.90 and 12.75 +/- 0.87 ng/JGA/h at 4 and 6 h. D-JGA renin activity increased (P less than 0.05) to 7.04 +/- 0.53, 6.23 +/- 0.31 and 3.44 +/- 0.33 ng/JGA/h at 2, 4 and 6 h after uranyl nitrate. Distal tubule [Na+], 27 samples in 6 rats, increased from a mean control value of 53.7 +/- 1.2 mEq/l to 116.9 +/- 2.5 mEq/l, 24 samples in 6 rats (P less than 0.001). Prompt increases in JGA renin activity were observed in the initiating phase of acute renal failure, suggesting a role for the renin-angiotensin system in the pathophysiology of this nephrotoxic model. The association of increased JGA renin activity and increased distal [Na+] is consistent with a role for the tubuloglomerular feedback mechanism in the initiating phase of uranyl nitrate induced acute renal failure in the rat.
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PMID:Distal Tubule [Na+] and juxtaglomerular apparatus Renin activity in uranyl nitrate induced acute renal failure in the rat. An evaluation of the role of tubuloglomerular feedback. 98 32

1. Sodium excretion, plasma renin acitivity (PRA), inulin clearance, total renal blood flow (RBF), renal cortical radiomicrosphere distribution and systemic administration of uranyl nitrate (19.9 mumol/kg body wt.; 10 mg/kg) in the dog. 2. During the 3 h of study after uranyl nitrate, urine flow remained stable or increased, sodium excretion increased approximately fivefold, renal vascular resistance increased threefold, and concordant decreases in RBF and inulin clearance to 40-50% of control values occured. At 3 h total cortical RBF decreased to 35% of control values and the ration of blood flow in outer to inner cortical zones also decreased, reflecting outer cortical ischaemia, PRA increased in the first hour after uranyl nitrate and slowly declined therafter, though not to control values. 3. Respiratory rate, heart rate, mean systemic blood pressure and cardiac output were unchanged after uranyl nitrate, demonstrating that the changes in renal vascular resistance occurred without a change in peripheral vascular resistance. 4. It is postulated that increased renin-angiotensin system activity mediates the change in renal haemodynamics and the consequent fall in glomerular filtration.
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PMID:Uranyl nitrate acute renal failure in the dog: early changes in renal function and haemodynamics. 111 82

Nicorandil is a vasodilator drug that combines potassium channel opening properties with nitrate effects. The resulting potent and unique vasodilating properties suggest a potential therapeutic role in congestive heart failure. We therefore studied the acute hemodynamic and neurohumoral responses to nicorandil, given as single intravenous bolus doses of 158, 251, 398, or 630 micrograms/kg, to 22 patients with chronic congestive heart failure (ejection fraction less than 40%). Hemodynamic responses occurred within 5 min of dosing and terminated within 240 min. The heart rate was significantly increased only at 5 min after the 158 micrograms/kg dose, and was unchanged after all other doses. The mean arterial pressure was reduced only by the 398 and 630 micrograms/kg doses. The pulmonary capillary wedge pressure and right atrial pressure were significantly reduced by all doses within the initial 30 min; this reduction in pulmonary capillary wedge pressure was better sustained over time by the two larger doses, whereas the reduction in right atrial pressure was sustained only by the 158 micrograms/kg dose. The cardiac index was reduced by the 158 micrograms/kg dose, but increased after 251, 398, and 630 micrograms/kg of nicorandil. Plasma nicorandil concentrations were positively correlated with changes in cardiac index, systemic arterial pressure, pulmonary capillary wedge pressure, heart rate, and systemic vascular resistance. When measured 1 h after dosing, plasma immunoreactive ANF decreased, norepinephrine concentrations did not change, and plasma renin activity increased, but only at the 630 micrograms/kg dose level.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemodynamic and neurohumoral responses to intravenous nicorandil in congestive heart failure in humans. 128 Jul 13

The sensitivity of renin release to changes in anion and calcium concentrations was assessed in superfused rat glomeruli with attached juxtaglomerular cells. Isosmotic substitution of Cl-with gluconate (1/12, 1/6, 1/3, 2/3, or total exchange), isethionate (15 or 101 mM), or sulfate (10 mM) inhibited renin release reversibly. Substitution of Cl- with nitrate (101 mM) stimulated renin secretion. Substitution with iodide (15 or 101 mM) had no consistent effect. The stimulation induced by calcium-free solutions was high in May and low in September. In the absence of chloride, the response to calcium-free solution was inhibited similarly all year. In May reintroduction of calcium and chloride stimulated renin release, suggesting that releasable renin had been stockpiled during the exposure to calcium-free solution. In September reintroduction of calcium and chloride inhibited renin release. It is concluded that the renin secretory process has a demand for permeant anions. The stimulation caused by low external calcium involves at least two mechanisms: one is anion sensitive, powerful, varies with the season, and includes a recruitment phenomenon; another is anion insensitive and weak.
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PMID:Involvement of chloride in renin secretion from isolated rat glomeruli. 155 58

1. It is now recognised that nitrate therapy designed to provide effects throughout 24 h each day induces tolerance. Such tolerance may be partial or complete and is associated with diminished haemodynamic and clinical effects. 2. The mechanism of tolerance is not completely understood but it seems to be related to the depletion of reduced sulphydryl groups in vascular smooth muscle and to the activation of counter-regulatory forces. These include elevated plasma catecholamines, arginine vasopressin and plasma renin activity. Activity of the renin-angiotensin system is associated with sodium and water retention and plasma volume expansion. The increase in vasoconstrictor influences and augmented plasma volume could modulate the effect of nitrate-induced vasodilatation.
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PMID:Update on nitrate tolerance. 163 72

To better understand the mechanism of nitrate tolerance in patients with congestive heart failure, 13 patients received a 24 h infusion of nitroglycerin (1.5 micrograms/kg body weight per min) with or without N-acetylcysteine (225 mg/kg per 24 h). The infusions were separated by a 24 h nitrate-free interval. By the end of the nitroglycerin infusion, mean arterial pressure had returned to baseline values and there was a significant increase in ventricular filling pressures and systemic vascular resistance compared with values after 1 h of treatment. The simultaneous infusion of N-acetylcysteine had no effect on these changes. Although a strict fluid restriction of 1.5 liters/day was maintained for 1 week before and throughout the study, after 24 h of nitroglycerin infusion there was a significant and similar degree of hemodilution whether nitroglycerin was infused alone (9.1 +/- 4.3%) or with N-acetylcysteine (8.7 +/- 4.1%). This hemodilution corresponded to an increase in intravascular volume of 745 +/- 382 ml, most of which occurred during the 1st h. Plasma renin activity increased and plasma atrial natriuretic peptide decreased during the infusion. The results of this study suggest that nitrate tolerance is multifactorial. In addition to the previously described pharmacologic tolerance to the effect of nitroglycerin on vascular smooth muscle, a capillary fluid shift from the extravascular to intravascular space appears to be involved, especially during the 1st h of the infusion. A third mechanism, reflex neurohumoral activation, also seems to contribute to the genesis of nitroglycerin tolerance.
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PMID:Tolerance to intravenous nitroglycerin in patients with congestive heart failure: role of increased intravascular volume, neurohumoral activation and lack of prevention with N-acetylcysteine. 197 62

Tolerance to treatment with nitrate derivatives, suspected for many years and often ignored in everyday clinical practice, has recently been the subject of much study. Although the phenomenon has been clearly demonstrated in patients on long-term therapy, it seems to vary from patient to patient, with the underlying pathology and the galenic form of nitrate used. The mechanism of tolerance to nitrates is multifactorial, related on the one hand to depletion of sulfhydryl groups in the body and on the other to activation of the sympathetic and renin-angiotensin systems. The administration of sulfhydryl groups in the form of N-acetylcysteine partially restores the effects of nitrates in some patients.
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PMID:[Tolerance of treatment with nitrate derivatives]. 211 76

The possible role of angiotensin-converting enzyme inhibition in preventing or minimizing tolerance to intravenous nitroglycerin in severe congestive heart failure (CHF) was studied by quantitating the degree of tolerance in 12 patients receiving nitroglycerin (group 1) and in 9 patients (group 2) receiving nitroglycerin and concurrent treatment with captopril (60 +/- 29 mg/day). At peak effect, nitroglycerin produced almost identical hemodynamic changes in both groups, with significant decreases in right atrial and pulmonary arterial wedge pressure, systolic blood pressure and systemic and pulmonary vascular resistances. Cardiac index increased. The extent of nitrate tolerance was calculated for each hemodynamic parameter as the percentage loss of the peak effect achieved by the drug. At 24 hours, 98 +/- 80% of the benefit achieved with respect to right atrial pressure was lost in group 1 and 61 +/- 74% in group 2 (group 1 vs 2, difference not significant). For pulmonary arterial wedge pressure, 51 +/- 31% (group 1) and 85 +/- 53% (group 2) (difference not significant) of the effect was lost, and for cardiac index, 53 +/- 58% (group 1) and 54 +/- 44% (group 2) (difference not significant). Tolerance was also almost identical regarding systolic blood pressure and systemic and pulmonary vascular resistance. Thus, the extent of tolerance to high-dose intravenous nitroglycerin in CHF was unaltered by administration of captopril, indicating that in clinical dosage, counter-regulatory neurohumoral mechanisms involving the renin-angiotensin system appear to be unimportant in its development.
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PMID:Failure of captopril to prevent nitrate tolerance in congestive heart failure secondary to coronary artery disease. 211 1


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