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 mesenteric arterial bed and the levels of cAMP and cGMP released from the rat mesenteric arterial bed. Perfusions of mesentery preparations with 1 muM acetylcholine, 0.1 muM calcium ionophore A23187, and 1 muM sodium nitroprusside all produced complete and long-lasting relaxation and increased the levels of cAMP as well as cGMP in the effluent. In endothelium-denuded preparations, acetylcholine did not elicit either vasorelaxation or an increase in cAMP and cGMP levels. Perfusion of the endothelium-denuded preparation with 1 muM sodium nitroprusside evoked complete relaxation and a marked increase in cGMP levels but not cAMP levels. Isoproterenol (1 muM) produced complete relaxation and an increase in cAMP levels, but did not affect cGMP levels either in the preparation with or in that without endothelium. Acetylcholine (0.001-1 muM) relaxed the preparation and increased cAMP and cGMP levels in the effluent in a dose-dependent manner. The acetylcholine-induced relaxation was reversed by 45% following perfusion with 10 muM methylene blue, and both the cAMP and cGMP levels were decreased. L-N(G)-Monomethyl arginine (L-NMMA) (100 muM), a nitric oxide synthase inhibitor, completely reversed the relaxation induced by 0.1 muM acetylcholine and reduced the elevated cGMP levels. Indomethacin (1 muM) reduced the acetylcholine-induced cAMP release, but did not alter the vasorelaxation in response to acetylcholine. We propose a novel method for the simultaneous measurement of vasodilation and changes in cAMP and cGMP levels released from the rat mesenteric arterial bed. We conclude that this method may provide information about the function of the endothelium of resistance vessels.