Histamine-mediated vasoconstriction and cAMP levels in coronary arteries of the isolated rabbit heart.

The role of adenosine 3',5'-monophosphate (cAMP) in histamine-mediated vasomotion of coronary vascular smooth muscle was studied in the isolated perfused rabbit heart. In paired physiological studies, histamine-mediated vasoconstriction, as indicated by change in perfusion pressure, was inhibited by the presence of either theophylline, a phosphodiesterase inhibitor, or forskolin, an adenylate cyclase activator. The inhibitory effect of theophylline, but not of forskolin, was removed with cimetidine (H2-receptor antagonist). In biochemical studies, coronary vessel cAMP was measured immediately after, and compared to, the vasomotor response to histamine alone and to histamine in the presence of forskolin, theophylline, diphenhydramine (H1-receptor antagonist) or cimetidine. These studies showed that cAMP levels correlate inversely with the vasoconstrictor response to histamine, indicating that stimulation of H1-receptors is associated with a reduction of cAMP and that H2-receptors modify this reduction.