Endothelium-dependent hyperpolarization in resting and depolarized mammaryand coronary arteries of guinea-pigs

1 The membrane potential responses in guinea-pig coronary and mammary arter ies attributable to endothelium-derived nitric oxide (NO), prostaglandin (P G) and hyperpolarizing factor (EDHF), and to exogenous NO and the prostacyc lin analogue, iloprost, were compared at rest and when depolarized with the thromboxane analogue, U46619. 2 In the coronary artery, stimulation of the endothelium with acetylcholine (ACh) evoked hyperpolarization attributable to NO and a PG with similar pD (2)s at rest and in the presence of U46619. However, in depolarized tissues , the pD(2) of the response attributed to EDHF required a 10 fold lower con centration of ACh compared with at rest. 3 In the mammary artery, lower concentrations of ACh were required to evoke NO- and EDHF-dependent hyperpolarizations in depolarized mammary artery co mpared with at rest, while PG-dependent hyperpolarization did not occur unt il the concentration of ACh was increased some 10 fold both at rest and in U46619. 4 The smooth muscle of the coronary artery of guinea-pigs was some 4 fold more sensitive to exogenous NO and iloprost than was the mammary art ery. 5 In conclusion, the membrane potential response in arteries at rest, that is, in the absence of constrictor, may be extrapolated to events in the pre sence of constrictor when NO and PG are under study. However, the sensitivi ty to ACh and the magnitude of the hyperpolarization attributed to EDHF obt ained in tissues at rest may underestimate these parameters in depolarized tissues.