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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:729.)
© 2001 American Heart Association, Inc.

Editorials

Interactions Between NO and cAMP in the Regulation of Vascular Tone

Kathryn Lamping

From the Department of Internal Medicine, University of Iowa and the VA Medical Center, Iowa City.

Correspondence to Kathryn Lamping, PhD, Medical Services (111), VA Medical Center, Iowa City, IA 52246. E-mail kathryn-lamping@uiowa.edu

Key Words: nitric oxide • cAMP • cGMP • coronary circulation • nitric oxide synthase

Amajor focus of studies in vascular biology has been the role of the endothelium in modulating tone of vascular smooth muscle by release of nitric oxide (NO), stimulation of soluble guanylate cyclase, and the subsequent increase in intracellular cyclic guanosine monophosphate (cGMP). An alternative second-messenger pathway that plays a key role in eliciting relaxation of vascular muscle involves receptor-mediated activation of adenylate cyclase, formation of cAMP, and activation of protein kinase A and myosin light-chain kinase within smooth muscle cells. In general, cAMP-mediated relaxation of vascular smooth muscle does not involve the endothelium. Although most studies suggest that vasorelaxation to many agents is mediated by release of cGMP or cAMP alone, several studies have suggested that some "typical endothelium-independent" vasodilators may also release NO and activate guanylate cyclase.^{1 2 3 4 5 6 7 8 9 10 11 12 13} Relaxation to some classic endothelium-independent agents, including adenosine, prostacyclin, forskolin, and ß-receptor agonists, is reduced by inhibitors of NO synthase (NOS).^{1 2 3 4 5 6 7 8 9 10 11 12 13} These studies suggest that relaxation of vascular smooth muscle to selected endothelium-independent agents is mediated by an interaction between cGMP and cAMP pathways.

Complex interactions between different vasodilator pathways in vascular smooth muscle have been proposed for cyclooxygenase and NOS. For example, inhibition of either cyclooxygenase or NOS abolished the increase in cerebral blood flow in response to hypercapnia.^{14 15} Acute or chronic inhibition of NOS enhanced the role of cyclooxygenase in the regulation of vascular resistance in the coronary and renal circulations.^{16 17 18} In the coronary circulation of humans with atherosclerosis, inhibitors of both NOS or cyclooxygenase reduced flow-mediated response.¹⁹ These studies . . . [Full Text of this Article]

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