Smooth muscle contractile diversity in the control of regional circulations

Abstract

Each regional circulation has unique requirements for blood flow and thus unique mechanisms by which it is regulated. In this review we consider the role of smooth muscle contractile diversity in determining the unique properties of selected regional circulations and its potential influence on drug targeting in disease. Functionally smooth muscle diversity can be dichotomized into fast versus slow contractile gene programs, giving rise to phasic versus tonic smooth muscle phenotypes, respectively. Large conduit vessel smooth muscle is of the tonic phenotype; in contrast, there is great smooth muscle contractile diversity in the other parts of the vascular system. In the renal circulation, afferent and efferent arterioles are arranged in series and determine glomerular filtration rate. The afferent arteriole has features of phasic smooth muscle, whereas the efferent arteriole has features of tonic smooth muscle. In the splanchnic circulation, the portal vein and hepatic artery are arranged in parallel and supply blood for detoxification and metabolism to the liver. Unique features of this circulation include the hepatic-arterial buffer response to regulate blood flow and the phasic contractile properties of the portal vein. Unique features of the pulmonary circulation include the low vascular resistance and hypoxic pulmonary vasoconstriction, the latter attribute inherent to the smooth muscle cells but the mechanism uncertain. We consider how these unique properties may allow for selective drug targeting of regional circulations for therapeutic benefit and point out gaps in our knowledge and areas in need of further investigation.