nitrophenols and Ischemia

Blockade of the T-type calcium channel (TCC), which is expressed in the renal efferent arterioles of the juxtamedullary nephron and vasa recta, has been shown to protect against renal injury. Studies were designed to determine the effects of a specific TCC blocker, R(-) efonidipine [R(-)EFO], on the regulation of renal circulation.. Renal medullary blood flux (MBF) and cortical blood flux (CBF) were simultaneously monitored using laser-Doppler flowmetry in Sprague-Dawley rats. Responses were also determined in rats with angiotensin II (AngII) induced renal ischemia. Intravenous (i.v.) or renal interstitial (r.i.) infusion of R(-)EFO (0.25 mg/h, i.v. or r.i.) significantly increased MBF by 24.0 ± 7.0 and 21.0 ± 4.4%, respectively, but without changing CBF or mean arterial pressure. The nitric oxide (NO) synthase inhibitor NG-nitro-L-argininemethylester (L-NAME, 1 μg/kg per min, i.v. or r.i.) significantly attenuated R(-)EFO-induced increase in MBF. R(-)EFO inhibited the AngII-mediated (50 ng/kg per min, i.v.) reduction of MBF (28.4 ± 1.7%), which was associated with increased urinary NO(2) + NO(3) excretion and decreased urinary hydrogen peroxide (H(2)O(2)) excretion. Intracellular H(2)O(2) fluorescence (real-time fluorescence imaging) in the epithelial cells of isolated medullary thick ascending limb (mTAL) significantly increased following AngII stimulation (1 μmol/L, 235 ± 52 units), which was significantly inhibited by pre and coincubation with R(-)EFO. R(-)EFO stimulation also increased the intracellular NO concentration in the epithelial cells of mTAL (220 ± 62 units).. These results suggest that TCC blockade with R(-)EFO selectively increases MBF, an effect that appears to be mediated by changes in renal NO and oxidative stress balance, which may protect against ischemic renal injury in the renal medullary region.

Topics: Angiotensin II; Animals; Blood Flow Velocity; Calcium Channel Blockers; Calcium Channels, T-Type; Dihydropyridines; Disease Models, Animal; Drug Antagonism; Infusions, Intravenous; Ischemia; Kidney Medulla; Laser-Doppler Flowmetry; NG-Nitroarginine Methyl Ester; Nitrogen Dioxide; Nitrogen Oxides; Nitrophenols; Organophosphorus Compounds; Rats; Rats, Sprague-Dawley; Renal Circulation; Vasoconstrictor Agents

1. We investigated the effect of efonidipine hydrochloride (NZ-105) against acute renal failure (ARF) in male Wistar rats. ARF was produced by ischemia or glycerol. 2. Ischemia-induced ARF was produced by right nephrectomy and clamping of the left renal artery for 60 min, followed by reperfusion. NZ-105 (20 mg/kg) was orally administered twice a day for 3 days before ARF. The plasma creatinine and urea nitrogen concentrations were markedly elevated in the ischemia ARF group on the 1st day, but the elevation was significantly suppressed by NZ-105 treatment. 3. Glycerol-induced ARF was produced by intramuscular injection of 50% (v/v) glycerol (10 ml/kg) in rats which were restricted to drinking water for 24 hr. NZ-105 (20 mg/kg) was orally administered twice a day for 3 days before ARF. NZ-105 significantly attenuated the severe impairment of creatinine and urea nitrogen clearances and the elevated fractional sodium excretion (FENa) caused by ARF. 4. In the kidney homogenate, NZ-105 (10(-6)-10(-4) M) inhibited lipid peroxidation induced by ascorbic acid and Fe or by NADPH and the inhibitory effect of NZ-105 was stronger than alpha-tocopherol, an antioxidant agent. NZ-105 (10(-5)-10(-3) M) showed radical scavenging action against diphenyl-p-picrylhydrazyl and galvinoxyl induced radicals. 5. These findings suggest that NZ-105 prevents the renal damage caused by the two kinds of ARF. Moreover, the inhibitory effects of NZ-105 against lipid peroxidation and radical formation may be one of the mechanisms involved in the prevention of ARF.

Topics: Acute Kidney Injury; Animals; Calcium Channel Blockers; Dihydropyridines; Diuretics; Free Radical Scavengers; Free Radicals; Glycerol; Ischemia; Kidney; Lipid Peroxidation; Male; Nitrophenols; Organophosphorus Compounds; Rats; Rats, Sprague-Dawley; Rats, Wistar

Topics: Acid Phosphatase; Animals; Blood Platelets; Centrifugation; Copper; Dogs; Erythrocytes; Ischemia; Leukocytes; Liver; Liver Circulation; Lysosomes; Microsomes, Liver; Mitochondria; Naphthalenes; Nitrophenols; Phosphorus; Sulfates; Tartrates

Topics: Adenosine Triphosphatases; Animals; Biological Transport; Cell Membrane; Hindlimb; Hydrogen-Ion Concentration; Ischemia; Lactates; Magnesium; Microsomes; Mitochondria, Muscle; Muscles; Nitrophenols; Ouabain; Potassium; Rats; Shock; Sodium

The results reported in this paper indicate that dinitrophenol acts directly on the isolated heart, increasing its metabolic rate. It also produces heart failure associated with a low phosphocreatine content of the muscle but with no change in adenosine triphosphate, which may or may not be due to a relative hypoxia of the cardiac tissue. Experimental arterial hypoxaemia, if severe, produces a similar picture of heart failure with a decrease in phosphocreatine and no change in adenosine triphosphate. Ligation of the coronary arteries results in disappearance of the major part of the phosphocreatine within a few minutes regardless of whether or not ventricular fibrillation ensues; the adenosine triphosphate remains unchanged.

Topics: Adenosine Triphosphate; Animals; Blood Circulation; Coronary Vessels; Dinitrophenols; Dogs; Heart; Heart Failure; Humans; Hypoxia; Ischemia; Myocardium; Nitrophenols; Phosphocreatine; Phosphorus; Phosphorus Compounds