N-nitro L-arginine causes coronary vasoconstriction and inhibits endothelium-dependent vasodilatation in anaesthetized greyhounds.
1. The effect of N-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide biosynthesis, on large coronary artery diameter and coronary blood flow was examined in anaesthetized greyhounds. The effects of L-NNA on the coronary vascular responses to acetylcholine (ACh), glyceryl trinitrate (GTN) and 5-hydroxytryptamine (5-HT) were also assessed. 2. L-NNA (5 mg kg-1), infused into the left circumflex coronary artery, increased systemic mean arterial pressure and decreased the external diameter of the artery. Infusion of L-NNA decreased coronary blood flow in 5 of the 7 dogs tested and increased mean coronary resistance but neither of these effects was statistically significant. There was no change in heart rate. 3. Intra-arterial injection of both ACh (0.01-0.05 micrograms kg-1) and GTN (0.1-0.5 micrograms kg-1) increased large coronary artery diameter and coronary blood flow. Coronary vascular responses to the endothelium-dependent vasodilator ACh were significantly reduced by L-NNA, whereas the responses to the endothelium-independent vasodilator GTN were not significantly affected. 4. 5-HT (0.1 microgram kg-1, injected into the left circumflex coronary artery) decreased coronary artery diameter but increased coronary blood flow. After the administration of L-NNA the 5-HT-induced dilatation of the coronary resistance vessels was significantly attenuated whereas the constriction of the circumflex coronary artery was increased in 3 out of 3 dogs in which diameter could be measured, although the latter effect was not statistically significant. 5. These data indicate that L-NNA causes coronary and systemic vasoconstriction and selectively inhibits endothelium-dependent vasodilatation in the coronary circulation of the anaesthetized greyhound. Therefore endothelium-derived NO has an important role in the regulation of coronary vascular tone in the large arteries and the resistance vessels.
Woodman
O L
OL
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Dusting
G J
GJ
D000109:Acetylcholine / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D019335:Nitroarginine; D005996:Nitroglycerin / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D019335:Nitroarginine; D012701:Serotonin; D001120:Arginine; D005996:Nitroglycerin; D000109:Acetylcholine