The Role of Cyclic Nucleotides in the Vasculature

Abstract

The role of cyclic AMP and GMP in the vasculature is reviewed with reference to contractile state, adrenergic receptors, occurrence and function in endothelial and smooth muscle cells, vascular disease and cellular sites of action. An attempt has been made to interpret the often conflicting and fragmented reports in order to summarize the present state of knowledge of this field. Evidence is presented supporting the thesis that, in vascular muscle, cyclic AMP is a mediator of β-adrenergic relaxation. The evidence is less complete for the involvement of cyclic AMP with other mediators of vascular muscle relaxation. Cyclic GMP also appears less likely to be a mediator or determinant of adaptive responses of vascular smooth muscle. The occurrence and possible function of cyclic nucleotides in vascular endothelial cells is discussed. The knowledge of hormonal control of this vascular cell type is in its infancy and thus far our understanding of the role of cyclic nucleotides is at a speculative stage. Studies which attempt to correlate cyclic AMP concentration in arterial tissue of hypertensive or arteriosclerotic animals with the altered vascular state of these disease are reviewed. These reports raise the possibility that cyclic nucleotide metabolism may be altered in such disease states. The site and biochemical mechanism(s) of action of cyclic AMP within vascular smooth muscle are discussed, with particular emphasis on the possible action of the nucleotide on calcium ion translocation.