Cardiovascular effects of basic fibroblast growth factor in rats.
We determined the effects of human basic fibroblast growth factor (bFGF) on blood pressure (BP) and heart rate (HR) in pentobarbital-anesthetized rats and examined the possible involvement of nitric oxide (NO) and prostanoids in these effects. Intravenous (i.v.) injections of bFGF (1, 7.5, and 15 micrograms/kg) induced dose-dependent short-lasting decreases in BP followed by a striking increase in BP and HR variability. The BP and HR increases in variability were closely related (r = 0.95; n = 20; p < 0.001). Pretreatment with a single intravenous (i.v.) dose of N omega-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg) almost suppressed (-90%) the cardiovascular effects of bFGF, an effect that was restored by a single dose of L-arginine (100 mg/kg i.v.). Similar suppression was observed with use of indomethacin (10 mg/kg i.v.). Indomethacin given 50-60 min after bFGF abolished the increased variability of BP and HR. We conclude that the BP decrease and the increase in BP and HR variability induced by bFGF involve release of both NO and vasoactive prostanoids.
Boussairi
E H
EH
Department of Physiology and Clinical Pharmacology, URA CNRS 1483, Faculty of Pharmacy, Lyon, France.
Sassard
J
J
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004347:Drug Interactions; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D011453:Prostaglandins; D016222:Fibroblast Growth Factor 2; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin