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

Abstract

1 The administration of arachidonic acid (AA) to the isolated perfused heart of the rat usually produced biphasic coronary responses characterized by initial vasoconstriction followed by prolonged vasodilatation. However, some responses were predominantly vasoconstrictor or vasodilator.2 The non-steroidal anti-inflammatory agents (NSAA) indomethacin (1-5mg/l) and naproxen (12.5-25 mg/I) reversibly inhibited both phases of the response induced by AA. 3 Pretreatment of animals with indomethacin (5 mg/kg) or naproxen (25 mg/kg) daily, resulted in unaltered coronary response to AA. Subsequent addition of NSAA to the perfusate produced inhibition of the AA effect. 4 Short infusions of acetylsalicylic acid at low concentrations (2.9 Lg/ml), dipyridamole (0.6 pg/ml) and sulphinpyrazone (28.7 pg/ml) selectively inhibited the vasoconstrictor phase of the response to AA. 5 It was confirmed that metabolic coronary dilatation induced by cardiostimulation was inhibited by prolonged AA administration; this effect was prevented by NSAA pretreatment. Reactive hyperaemic responses to short lasting occlusions of coronary inflow were unaffected by NSAA. 6 Linolenic, linoleic, dihomo-y-linolenic and oleic acid usually produced decreases in coronary flow which were unaffected by NSAA, dipyridamole or sulphinpyrazone. 7 Intra-aortic injections of AA, prostacyclin (PGI2) and prostaglandin E2 (PGE2) in the intact rat produced a dose-dependent decrease in blood pressure with the AA response inhibited by indomethacin. PGI2 and PGE2 produced long lasting coronary vasodilatation in the isolated heart. 8 The coronary actions of AA appear to be due to its transformation, within the easily accessible vascular wall, into prostaglandin and thromboxane-like substances. We suggest that a vasoconstrictor thromboxane A2-like substance may be responsible for coronary vasospasm. 9 Coronary insufficiency may also result from an inhibition of compensatory metabolic coronary dilatation by increased synthesis of PGE2 within the myocardial cell.

Changes in cardiovascular sensitivity of alloxan‐treated diabetic rats to arachidonic acid

“…Both effects appeared to be indirect, mediated at least in part by production of products of cyclo-oxygenase, since they were reduced after administration of indomethacin. It has been found, that arachidonic acid has both indirectly mediated vasoconstrictor and vasodilator properties in the coronary arteries of the rat (Belo & Talesnik, 1982) and also the dog (Sterin-Borda et al, 1981). During diabetes, apparent conversion of arachidonic acid to depressor metabolites in the whole animal continued to predominate but the contribution made by the constrictor metabolite or metabolites appeared to increase.…”

Cardioprotective Effects of Omega-3 Polyunsaturated Fatty Acids: Dichotomy between Experimental and Clinical Studies

“…A meta-analysis suggested that linoleic acid (LA) content was inversely related to CHD risk [ 51 ], and a clinical study concluded that high circulating LA levels were inversely associated with total and CHD mortality in older adults [ 52 ]. In contrast, it has been reported that AA and its metabolites possess proinflammatory and proaggregatory properties [ 53 , 54 , 55 ]. Others argue that omega-6 and omega-3 PUFA are metabolized by the same desaturation/elongation pathway and could thus influence long-chain PUFA content, which could reduce the beneficial effect of omega-3 PUFA.…”

Vasodilator actions of acetylcholine, A23187 and bradykinin in the guinea‐pig isolated perfused heart are independent of prostacyclin

“…These observations suggest a vasodilator action on the microvasculature of the guinea-pig perfused heart. It is well established that PGI2 decreases coronary flow in isolated hearts from rabbits, rats and guineapigs and that PGI2 generation is increased by a range of stimuli including exogenous arachidonic acid (Schror et al, 1978;Belo & Talesnik, 1982), hypoxia (Wennmalm, 1979), Paf (Piper & Stewart, 1986) and ATP (Fleetwood & Gordon, 1987). Since the ability of both bradykinin and the ionophore, A23187, to stimulate PGI2 generation from cultured endothelial cells (McIntyre et al, 1985;Gryglewski et al, 1986;Gerritsen, 1987) and isolated perfused lungs (Bakhle et al, 1985) is well recognized, it was important to determine whether these stimuli had a similar effect in the perfused heart and also to identify a possible contribution to the observed vasodilator responses.…”