SIMULTANEOUS MEASUREMENT OF VASODILATION AND CHANGES IN CYCLIC-NUCLEOTIDES IN THE PERFUSED MESENTERIC ARTERIAL BED OF THE RAT

We examined the relationship between relaxation responses of the mesen teric arterial bed and the levels of cAMP and cGMP released from the r at mesenteric arterial bed. Perfusions of mesentery preparations with 1 muM acetylcholine, 0.1 muM calcium ionophore A23187, and 1 muM sodiu m nitroprusside all produced complete and long-lasting relaxation and increased the levels of cAMP as well as cGMP in the effluent. In endot helium-denuded preparations, acetylcholine did not elicit either vasor elaxation or an increase in cAMP and cGMP levels. Perfusion of the end othelium-denuded preparation with 1 muM sodium nitroprusside evoked co mplete relaxation and a marked increase in cGMP levels but not cAMP le vels. Isoproterenol (1 muM) produced complete relaxation and an increa se in cAMP levels, but did not affect cGMP levels either in the prepar ation with or in that without endothelium. Acetylcholine (0.001-1 muM) relaxed the preparation and increased cAMP and cGMP levels in the eff luent in a dose-dependent manner. The acetylcholine-induced relaxation was reversed by 45% following perfusion with 10 muM methylene blue, a nd both the cAMP and cGMP levels were decreased. L-N(G)-Monomethyl arg inine (L-NMMA) (100 muM), a nitric oxide synthase inhibitor, completel y reversed the relaxation induced by 0.1 muM acetylcholine and reduced the elevated cGMP levels. Indomethacin (1 muM) reduced the acetylchol ine-induced cAMP release, but did not alter the vasorelaxation in resp onse to acetylcholine. We propose a novel method for the simultaneous measurement of vasodilation and changes in cAMP and cGMP levels releas ed from the rat mesenteric arterial bed. We conclude that this method may provide information about the function of the endothelium of resis tance vessels.