Prostaglandins and the control of blood flow in the canine myocardium.

Abstract

SUMMARY A comprehensive study was undertaken to evaluate the effects of inhibition of prostaglandin (PG) synthesis on a variety of reactions in the coronary vascular bed of anesthetized, open-chest dogs. In 23 dogs an electromagnetic flow probe (EMFP) and hydraulic occluder were placed around either the left anterior descending or circumflex branches of the coronary artery and a needle was inserted distal to the EMFP. Injections into the coronary artery of arachidonic acid (AA), bradykinin, adenosine, angiotensin, and PGE 2 were given before and after inhibition of PG synthesis by indomethacin (IND) or meclofenamate (MF). The effects of the inhibitors on reactive hyperemia resulting from S-, 10-, 15-, and 20-second occlusions and the dilation resulting from 90-second exposure to 8% O 2 were also examined. In each experiment, inhibition of PG synthesis was ascertained by the elimination of vasodilation to AA. After administration of IND or MF, while baseline coronary blood flow was slightly reduced, the total increment of blood flow to vasodilator agents was not significantly altered. Whereas the peak dilation and volume of reactive hyperemia were decreased, the percent flow debt repaid was unchanged and total increment of coronary flow due to hypoxia-induced vasodilation was not significantly modified. Vasoconstrictor responses to angiotensin were also unchanged. These results indicate that while inhibitors of PG synthesis increase coronary resistance, they do not adversely affect vascular responsiveness. We conclude that prostaglandins play little, if any, role in modulating coronary blood flow.A NUMBER of reports assign an important role for prostaglandins in the regulation of coronary blood flow. The recent discovery that the nonsteroidal anti-inflammatory agents have in common the ability to inhibit prostaglandin (PG) synthesis' has made possible the study of the physiological role of these agents in a number of circulatory beds. The ubiquity of prostaglandins in tissues, 2 their release after pharmacological stimulation of vascular tissue, and the reduction in blood flow after the administration of inhibitors of PG synthesis 3 are all factors that support the hypothesis that prostaglandins of the E series, which are generally vasodilator, 2 are important modulators of vascular tone. Whether prostaglandins subserve this function in the coronary vascular bed, however, is still open to question.It was reported recently that prostaglandins not only are released into the myocardial circulation during episodes of hypoxia, 4 anoxia, 5 and following coronary artery occlusion 6 -7 or administration of bradykinin, 8 but also that the ensuing increase in blood flow is attenuated in the presence of PG synthesis inhibitors. Other investigators, using similar experimental techniques, have found that the inhibitors had no significant effect on the vascular responses of coronary blood vessels. 9 In view of this controversy, we undertook a comprehensive study to investigate the possible role of endogenously produced prostag...

Coronary Vasoconstrictor and Vasodilator Actions of Arachidonic Acid in the Isolated Perfused Heart of the Rat

“…Furthermore, an infusion of indomethacin produced blockade of the coronary actions as well as the PGL efflux (Schror, Moncada, Ubatuba & Vane, 1978). These data corroborate previous experiments in which NSAA was administered to inhibit prostaglandin synthetase in isolated perfused or intact hearts (Minkes, Douglas & Needleman, 1973;Needleman, 1976;Hintze & Kaley, 1977). Other polyunsaturated fatty acids have also been reported to produce changes in coronary flow and in the output of PGL (Mentz & Forster, 1977).…”

Decreased contractile efficiency and increased nonmechanical energy cost in hyperthyroid rabbit heart. Relation between O2 consumption and systolic pressure-volume area or force-time integral.

“…Also, previous studies have shown that indomethacin does not affect coronary vascular responsiveness. 19 Our preliminary study in seven other normal rabbit hearts without any inotropic intervention showed that left ventricular peak isovolumic pressure at a constant ventricular volume at 90 and 120 minutes after an initial measurement (+0.4+10.0% and -6.2±15.4%, respectively) did not significantly differ from the initial value of 98+13 mm Hg. This indicates stability of our cross-circulated heart preparation compared with crystalloid-perfused hearts.…”

Prostacyclin, thromboxane A2, and prostaglandin E2 formation in atherosclerotic human carotid artery.

“…PGE 2 reportedly promotes the second phase of platelet aggregation. 23 ' 24 While it is doubtful that unregulated PGE 2 formation by spontaneous hydrolysis of PGH 2 contributes to carotid arterial thromboregulatory mechanisms, PGE 2 formed nonenzymatically could oppose platelet inhibitory effects of PGI 2 . Previous work in our laboratory, which unmasked the presence of GSH-dependent PGE 2 isomerase activity in bovine coronary artery microsomes, demonstrated the need for appropriately controlled experiments before the presence of GSH-dependent PGE 2 isomerase in vascular tissues could be definitely excluded.…”