title: Effects of captopril on cardiac and renal damage, and metabolic alterations in the nitric oxide-deficient hypertensive rat.
abstract: Chronic inhibition of nitric oxide (NO) synthesis is characterized by increased blood pressure accompanied with both cardiac hypertrophy as well as renal damage. We investigated whether the angiotensin-converting enzyme (ACE) inhibitor captopril can inhibit the cardiac hypertrophy and reverse the renal failure. We tested the influence of captopril on the nitrate-nitrite (NO(x)) in plasma and heart and kidney tissues. Oxidative stress, in terms of glutathione and thiobarbituric acid-reactive substances measured as malondialdehyde, was monitored examining their involvement in the cardioprotective and renoproptective actions. Three groups of Wistar rats were used: untreated group, and rats treated with the NO synthase inhibitor N(w)-nitro-L-arginine methyl ester (L-NAME) and L-NAME plus captopril (10 mg/kg/day). Systolic, diastolic and mean blood pressure (BPs, BPd and BPm respectively) was measured weekly in addition to the heart rate using rat-tail plethysmography. After 3 weeks, L-NAME significantly increased BPs, BPd and BPm. Captopril treatment reversed the increments in pressure back to normal values by the fourth week. ACE inhibition by captopril reverted the L-NAME-induced hypertrophy and inhibited the enzymatic indices of cardiac damage (glutamate oxaloacetate transaminase and lactate dehydrogenase) back to normal values. Furthermore, the NO synthesis inhibition produced renal damage as indicated by significant increase in creatinine. Captopril ameliorated the raised creatinine to normal. Chronic L-NAME treatment increased serum NO(x) levels but concomitant treatment with captopril was without effect.
authors.affiliation: Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. mahkhattab@yahoo.com
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: Khattab
authors.forename: Adel
authors.initials: A
authors.lastname: Mostafa
authors.forename: Othman
authors.initials: O
authors.lastname: Al-Shabanah
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D006332:Cardiomegaly / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003404:Creatinine / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D008315:Malondialdehyde; D002216:Captopril; D003404:Creatinine; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D001219:Aspartate Aminotransferases; D007703:Peptidyl-Dipeptidase A; D005978:Glutathione; D019331:NG-Nitroarginine Methyl Ester