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Vasodilator actions of acetylcholine, A23187 and bradykinin in the guinea‐pig isolated perfused heart are independent of prostacyclin
Author(s) -
Stewart Alastair G.,
Piper Priscilla J.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11656.x
Subject(s) - bradykinin , coronary vasodilator , vasodilation , prostacyclin , verapamil , acetylcholine , endothelium derived relaxing factor , medicine , endocrinology , chemistry , endothelium , pharmacology , calcium , receptor
1 The involvement of prostacyclin (PGI 2 ) in the vasodilator responses to acetylcholine (ACh), A23187 and bradykinin (Bk) has been investigated in guinea‐pig, isolated, Krebs‐perfused hearts. 2 ACh (0.01–10 nmol), A23187 (0.1–1.0 nmol) and Bk (0.3–10 pmol) 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 PGI 2 as measured by its chemically‐stable breakdown product, 6‐oxo‐PGF 1α . Indomethacin (2.8 μ m ) prevented both basal and the stimulated generation of 6‐oxo‐PGF 1α , 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 (3 μ m ) or diethylcarbamazine (300 μ m ), attenuated vasodilator responses to ACh without altering those to the endothelium‐independent vasodilator, verapamil (1 nmol). 5 Haemoglobin (10 μ m ) 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.