Ramipril prevents the detrimental sequels of chronic NO synthase inhibition in rats: hypertension, cardiac hypertrophy and renal insufficiency

Abstract

Inhibition of the angiotensin converting enzyme (ACE) with ramipril was studied in male Wistar rats during long-term inhibition of nitric oxide (NO) synthase by NG-nitro-L-arginine methyl ester (L-NAME). Chronic treatment with L-NAME in a dose of 25 mg/kg per day over 6 weeks caused myocardial hypertrophy and a significant increase in systolic blood pressure (245 +/- 16 mmHg) as compared to controls (155 +/- 4 mmHg). Animals receiving simultaneously L-NAME and ramipril were protected against blood pressure increase and partially against myocardial hypertrophy. L-NAME caused a significant reduction in glomerular filtration rate (GFR: 2.56 +/- 0.73 ml.kg-1.min-1) and renal plasma flow (RPF: 6.93 +/- 1.70 ml.kg-1.min-1) as compared to control (GFR: 7.29 +/- 0.69, RPF: 21.36 +/- 2.33 ml.kg-1.min-1). Addition of ramipril prevented L-NAME-induced reduction in GFR and renal plasma flow. L-NAME produced an elevation in urinary protein excretion and serum creatinine and a decrease in potassium excretion which was antagonised by ramipril. L-NAME-induced increase in plasma renin activity (PRA) was further elevated with ramipril treatment. Isolated hearts from rats treated with L-NAME showed increased post-ischaemic reperfusion injuries. Compared to controls duration of ventricular fibrillation was increased and coronary flow reduced. During ischemia the cytosolic enzymes lactate dehydrogenase and creatine kinase, as well as lactate in the venous effluent were increased. Myocardial tissue values of glycogen, ATP, and creatine phosphate were decreased, whereas lactate was increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Captopril in L‐Name‐Induced Hypertension on the Rat Myocardium, Aorta, Brain and Kidney

“…Protein synthesis may be affected in all cell types, while cell division has been found to occur in certain cells of different tissues: fibrocytes in the LV (Pelouch et al 1994), smooth muscle cells and fibrotic cells in the aorta, mesangial cells in the kidney (Hropot et al 1994), and conceivably fibrocytes in the brain. In our previous work (Bab al et al 1997), proliferation cell nuclear antigen immunohistochemistry indicated positive cells in the fibrotic tissue of the myocardium as well as in the media of coronary arteries and aorta.…”

Antihypertensive and cardioprotective effects of theLagenaria sicerariafruit inNG-nitro-L-arginine methyl ester (L-NAME) induced hypertensive rats

“…Hypertension is a major risk factor of IHD. N G -nitro-l-arginine methyl ester (l-NAME) has been used to induce hypertension in rats by Hropot et al (1994).…”

Renal Antioxidant Status in Rats with Hypertension Induced by N Sup Omega Nitro-<i>L</i>-Arginine Methyl Ester

“…It has been established that pharmacological inhibition of NO synthesis produces acute and chronic hypertension in many animal species [7,8]. Chronic administration of L-NAME has been implicated in the increased systolic blood pressure and decreased renal function [9].…”