Coronary blood flow in rats is dependent on the release of vascular nitric oxide.
The present study evaluated the role of nitric oxide (NO) in determining basal coronary vascular tone and the mechanism by which NO regulates coronary blood flow. Sprague-Dawley rats were anesthetized and instrumented for recording arterial pressure (AP), heart rate (HR) and coronary blood flow (CBF; Doppler). In rats without ventricular pacing, N-nitro-L-arginine methyl ester (LNAME) (10 mumol/kg, i.v.), an inhibitor of NO synthesis, produced an increase in AP and a decrease in HR. The LNAME-induced bradycardia was inhibited by sinoaortic denervation. LNAME also produced a reduction in left anterior descending (LAD) CBF. When the same dose of LNAME was administered to a separate group of rats measuring CBF in the right coronary artery (RCA), the decrease in CBF was found to be more prominent in the LAD compared to the RCA. Removal of the sympathetic innervation to the heart and adrenal demedullation did not alter the decrease in CBF, indicating that the effects of LNAME were not centrally mediated. To determine if the effect of LNAME on CBF was due to a direct action on the coronary vasculature or was secondary to the change in HR, dose-response curves were performed for LNAME (0.3-300 mumol/kg, i.v.) in rats with ventricular pacing. Under these conditions, LNAME still produced an increase in AP and a decrease in CBF, resulting in an increase in coronary vascular resistance. Administration of L-arginine (100-300 mg/kg, i.v.) resulted in a reversal of the cardiovascular effects of LNAME with the reversal being sustained for 1 to 5 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Jones
L F
LF
Department of Pharmacology, University of Iowa, Iowa City.
Brody
M J
MJ
D000313:Adrenal Medulla / Q000502:physiology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012849:Sinoatrial Node / Q000502:physiology; D013233:Stellate Ganglion / Q000601:surgery; D013562:Sympathectomy
D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester