Enhancement of noradrenergic constriction of large coronary arteries by inhibition of nitric oxide synthesis in anaesthetized dogs.
1. Coronary vascular responses to bilateral carotid occlusion (BCO) and the intravenous infusion of tyramine (Tyr, 20 micrograms kg-1 min-1) and noradrenaline (NA, 0.5 microgram kg-1 min-1) were examined after bilateral vagotomy and antagonism of beta-adrenoceptors. BCO, Tyr and NA decreased large coronary artery diameter and increased mean coronary resistance and systemic arterial pressure without affecting heart rate. 2. Inhibition of nitric oxide (NO) synthase with NG-nitro-L-arginine (L-NNA, 5 and 15 mg kg-1) significantly increased mean arterial pressure and decreased heart rate and large coronary artery diameter. Mean coronary resistance was unaffected by either dose of L-NNA. L-NNA significantly reduced depressor and coronary vasodilator responses to the endothelium-dependent vasodilator acetylcholine (ACh, 10 micrograms kg-1, i.v.). Systemic and coronary vasodilator responses to sodium nitroprusside (SNP, 5 micrograms kg-1) were unaffected by L-NNA with the exception that the dilatation of the large coronary artery was significantly enhanced by the higher dose. 3. L-NNA significantly enhanced constriction of the large coronary arteries caused by BCO, Tyr and NA but did not affect the increases in mean coronary resistance or systemic arterial pressure. 4. Inhibition of NO synthesis enhances adrenergic constriction of large coronary arteries caused by both neuronally released and exogenous noradrenaline. In contrast, L-NNA did not affect adrenergic constriction of coronary or systemic resistance vessels. Endothelium-derived NO may play an important role in the modulation of noradrenergic vasoconstriction in coronary conductance arteries.
Woodman
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Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Pannangpetch
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D000109:Acetylcholine / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D005260:Female; D007262:Infusions, Intravenous; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology; D014439:Tyramine / Q000494:pharmacology; D014628:Vagotomy; D014661:Vasoconstriction / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine; D009638:Norepinephrine; D014439:Tyramine