Influence of inhibition of endothelium-derived nitric oxide formation to effects of vasoconstrictor agents neuropeptide Y, clonidine, and ergonovine on coronary vascular resistance.
To determine whether inhibition of endothelium-derived nitric oxide (EDNO) synthesis enhances the effects of exogenous vasoconstrictor agents on the coronary vasculature, we examined the effects of neuropeptide Y (NPY), clonidine, and ergonovine on coronary vascular resistance (CVR) with and without EDNO inhibitor and compared the results. In 15 anesthetized mongrel dogs, the left circumflex coronary artery (LCX) was perfused with arterial blood from the left common carotid artery through an extracorporeal bypass tube and LCX blood flow was measured with an electromagnetic flowmeter. Nine of the dogs were pretreated with intracoronary NG-nitro-L-arginine methyl ester (L-NAME 300 microM in LCX blood) (L-NAME group) and the other 6 were treated with normal saline (vehicle group). Three doses of NPY (4.3, 43, 430 ng/kg), two doses of clonidine (30 and 300 ng/kg), and one dose of ergonovine (20 micrograms/kg) were infused into LCX. NPY decreased LCX flow and increased CVR dose dependently in both groups, and there was no significant difference in the dose-response relation between the two groups. Clonidine decreased LCX flow and increased CVR in both groups, and there was no difference in the effect between the groups. In contrast, ergonovine decreased LCX flow and increased CVR to a greater degree in the L-NAME group than in the vehicle group (p < 0.01). Thus, inhibition of EDNO synthesis by L-NAME did not result in enhancement of the vasoconstrictor effects of NPY and clonidine, whereas it significantly enhanced the effect of ergonovine, possibly through inhibition of ergonovine-induced EDNO release.
Tsunoda
R
R
Division of Cardiology, Kumamoto University School of Medicine, Japan.
Okumura
K
K
Ishizaka
H
H
Matsunaga
T
T
Yasue
H
H
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004874:Ergonovine / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009478:Neuropeptide Y / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D014655:Vascular Resistance / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D009478:Neuropeptide Y; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D001120:Arginine; D003000:Clonidine; D019331:NG-Nitroarginine Methyl Ester; D004874:Ergonovine