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

Abstract

1 The involvement of prostacyclin (PGI2) in the vasodilator responses to acetylcholine (ACh), A23187 and bradykinin (Bk) has been investigated in guinea-pig, isolated, Krebs-perfused hearts. 2 ACh (0.01-lOnmol), A23187 (0.1-1.Onmol) and Bk (0.3-lOpmol) each elicited dose-related and shortlasting (-2 min) reductions in perfusion pressure. Larger maximal responses were obtained in preparations with coronary vascular tone elevated by platelet-activating factor (100 pmol) than in preparations at basal perfusion pressure. 3 Bk and A23187 elicited dose-related increases in the generation of PGI2 as measured by its chemically-stable breakdown product, 6-oxo-PGFg. Indomethacin (2.8 uM) prevented both basal and the stimulated generation of 6-oxo-PGF,., whereas the magnitudes of the vasodilator responses were unaffected. 4 Attempts to identify the release of vasodilator materials by on-line superfusion bioassay of cardiac effluent were unsuccessful, indicating a possible role for a labile vasodilator such as endothelium-dependent relaxing factor (EDRF). In addition, the inhibitors of EDRF action/ production, mepacrine (3yM) or diethylcarbamazine (300pM), attenuated vasodilator responses to ACh without altering those to the endothelium-independent vasodilator, verapamil (1 nmol). 5 Haemoglobin (10pM) reduced vasodilator responses to ACh, Bk and verapamil and abolished those induced by A23187. Inhibition of the endothelium-independent vasodilator, verapamil, was significantly less than that for the other compounds. 6 The present data indicate the existence of an indomethacin-resistant vasodilator mechanism in the coronary microcirculation in response to ACh, A23187 and Bk. EDRF is a candidate for mediating these responses; however, a direct vasodilator action of these substances cannot be excluded.

Severe Hypoxia Inhibits Prostaglandin I₂ Biosynthesis and Vasodilatory Responses Induced by Ionophore A23187 in the Isolated Rabbit Ear

“…1b). This is consistent with the finding of other authors showing that the vasodilatory action of ionophore A23187 in the isolated guinea pig heart has been independent of the PGI 2 release [24].…”

Cyclic ADP ribose-mediated Ca2+signaling in mediating endothelial nitric oxide production in bovine coronary arteries

“…These results suggest that cADPR-mediated Ca 2ϩ signaling plays an important role in the regulation of endothelial NO production and thereby plays a critical role in EDVD. It is well known that the EDVD is of importance in the regulation of coronary circulation, which is involved in the actions of increased vasoactive agents such as arachidonic acid (41), ATP (4,28), acetylcholine (1), A-23187 (46), and BK (7,40). Both BK-and A-23187-induced vasodilation is linked to the release of endothelium-derived NO (7,40), prostaglandin I 2 (38), and endothelium-dependent hyperpolarizing factor, such as epoxyeicosatrienoic acids (6), and BK is considered as a more classic Ca 2ϩ -dependent activator of eNOS (5,53).…”

Coronary Hemodynamics in Endothelial NO Synthase Knockout Mice

“…32 However, the relative contribution of each of these mediators to the ACh-induced flow response varies considerably among species. Whereas in the guinea pig heart, ACh-induced vasodilation is dependent mainly on NO, 33 a concerted action of PGI 2 and NO was reported to mediate the response in the rabbit heart. 34 In the mouse heart, ACh induces an initial rapid vasoconstriction, which is evident at the beginning of the flow response, followed by a vasodilation, which dominates the flow in the steady state.…”