Contribution of nitric oxide to the beneficial effects of enalapril in the fructose-induced hyperinsulinemic rat.
We examined accumulating evidence of the positive contribution of nitric oxide to the pharmacological effects of converting enzyme inhibitors in 36 rats rendered hypertensive, hyperinsulinemic, and hypertriglyceridemic by a fructose-enriched diet. We studied the response of blood pressure, insulin, and triglyceride levels to inhibition of either converting enzyme-kininase II, nitric oxide synthase, or both. Two weeks of the converting enzyme inhibitor enalapril (20 mg/kg) reduced blood pressure from 137 +/- 2 to 105 +/- 7 mm Hg, insulin from 7.6 +/- 2.0 to 2.2 +/- 1.1 pg/mL, and triglycerides from 292 +/- 37 to 163 +/- 37 mg/dL. Treatment with NG-nitro-L-arginine methyl ester (100 mg/kg) raised blood pressure from 144 +/- 7 to 170 +/- 8 mm Hg without affecting the other parameters. Two weeks of concomitant treatment with both agents blunted the hypotensive and beneficial metabolic effects of enalapril; thus, final blood pressure (141 +/- 7 mm Hg), insulin (6.4 +/- 2.4 pg/mL), and triglyceride (231 +/- 51 mg/dL) values were no different from those of untreated fructose-fed rats. These data suggest that persistent synthesis of nitric oxide contributes to the vasodilator and metabolic effects of enalapril in the fructose-fed rat model.
Chorley Hypertension Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel.
Y
Y
Erlich
T
T
Rosenthal
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D004357:Drug Synergism; D004656:Enalapril / Q000627:therapeutic use*; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects*; D006946:Hyperinsulinism / Q000139:chemically induced* / Q000188:drug therapy; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use; D009569:Nitric Oxide / Q000096:biosynthesis / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood*
D000806:Angiotensin-Converting Enzyme Inhibitors; D014280:Triglycerides; D005632:Fructose; D009569:Nitric Oxide; D004656:Enalapril; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester