Histamine-Mediated Vasoconstriction and cAMP Levels in Coronary Arteries of the Isolated Rabbit Heart

Abstract

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 H₂-receptors is associated with a reduction of cAMP and that H2-receptors modify this reduction.

Function and Role of Histamine H1 Receptor in the Mammalian Heart

“…Receptor binding studies have revealed histamine H 1 receptors in bovine aortic smooth muscle cells [ 139 ]. The vasoconstrictory effects of histamine H 1 receptor stimulation in rabbit coronary arteries were accompanied by a decrease in cAMP levels measured in these arteries [ 140 ]. This was interpreted as evidence of a direct or indirect inhibitory action of histamine H 1 receptors on adenylyl cyclase activity [ 140 ].…”