Attenuation of coronary autoregulation in the isolated rabbit heart by endothelium derived nitric oxide.
OBJECTIVE
The aim was to investigate the role of endothelium derived nitric oxide (EDNO/EDRF) in the control of coronary autoregulation.


METHODS
In isolated saline perfused rabbit hearts coronary flow responses to stepwise increases in perfusion pressure were studied under control conditions, during maximum dilatation with sodium nitroprusside, and in the presence of the inhibitor of EDNO synthesis, NG-nitro-L-arginine (L-NNA), or the vasoconstrictors endothelin-1 and arginine vasopressin.


RESULTS
At a constant perfusion pressure of 60 mm Hg, infusion of L-NNA (30 microM), but not D-NNA, reduced the coronary flow from 24.7(SEM 2) to 13.6(2.2) ml.min-1 and abolished flow increases induced by the EDRF stimulator acetylcholine. Under these conditions, pressure induced coronary flow increases were reduced (p < 0.05 compared to control) over the whole range of perfusion pressures studied (45 to 120 mm Hg). Arginine vasopressin [2(0.6) nM] and endothelin-1 [1.5(1) nM] induced similar reductions of coronary resting flow but the pressure induced flow increases were significantly greater than in the presence of L-NNA. Moreover, inhibition of EDRF synthesis reduced the peak reactive hyperaemia after a 30 s interruption of coronary flow from 47(2) to 32(2) ml.min-1. These changes occurred in spite of a decrease in the myocardial oxygen uptake from 5.1(0.6) to 3.4(0.5) ml.100 g-1.min-1 (p < 0.01) and a concomitant increase in the lactate release from 46(7) to 95(54) mumol.min.100 g-1 (p < 0.01), indicating myocardial ischaemia.


CONCLUSIONS
EDNO attenuates coronary autoregulatory responses which, if unopposed, potentially impair a functionally adequate myocardial perfusion. It is suggested that the modulator role of EDNO is, at least in part, specific and most likely to be due to shear dependent alterations of EDNO release.
Pohl
U
U
Institut für Physiologie, Medizinische Universität zu Lübeck, Germany.
Lamontagne
D
D
Bassenge
E
E
Busse
R
R
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D016232:Endothelins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006706:Homeostasis / Q000187:drug effects*; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000494:pharmacology*; D019335:Nitroarginine; D010477:Perfusion; D011817:Rabbits; D017725:Ventricular Pressure
D016232:Endothelins; D001127:Arginine Vasopressin; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine