Cyclic nucleotides in disease; on the biochemical etiology of hypertension.

The importance of cyclic nucleotide aberrations and the central role of nucleotidyl cyclase hormonal sensitivity in disease are outlined. The hypothesis is presented that sustained increases in sympathetic nerve activity or renin-angiotensin levels early in the development of hypertension may lead to the irreversible loss of vascular adenylyl cyclase hormonal sensitivity coupled with increased phosphodiesterase activity. This leads to increased cyclic GMP: cyclic AMP ratio in the vasculature which translates into elevated vascular smooth muscle tone and sensitivity and mediates the increased vascular smooth muscle proliferation that results in increased wall to lumen ratio. Both these effects underlie the increased peripheral resistance that maintains the hypertensive state.