Nonreceptor-mediated intestinal vasoconstriction in portal hypertensive rats.

Abstract

Previous studies have demonstrated that receptor-mediated vasoconstriction is impaired in chronic portal hypertension (PH). Furthermore, it has been suggested that altered vasoconstrictor effectiveness in chronic PH is due to a defect in the intracellular events associated with smooth muscle activation and not to impaired coupling of vasoconstrictors with vascular smooth muscle receptors. The present study was designed to determine whether nonreceptor-mediated vasoconstrictor responses are impaired in the PH intestinal microcirculation. Specifically, we examined the effects of aluminum fluoride-induced activation of G proteins, KCl-induced depolarization, caffeine-induced release of intracellular Ca2+, and l-indolactam-induced activation of protein kinase C on the intestinal microcirculation of normal (Norm, n = 39) and PH (n = 42) rats. The small intestine was prepared for microcirculatory studies and transferred to a video microscope. First-order arteriolar (1A) diameter and red cell velocity were measured on-line. Blood flow was calculated from the product of velocity and microvessel cross-sectional area. After a control period, the microvasculature was exposed to a solution containing aluminum chloride plus sodium fluoride, potassium chloride, caffeine, or l-indolactam. Maximal decreases in arteriolar diameter produced by aluminum fluoride, KCl, caffeine, and l-indolactam were significantly greater in Norm rats when compared with PH rats. Changes in arteriolar blood flow were also larger in Norm than in PH rats. The results of the present study provide the first direct evidence of an impaired response to second-messenger activation in the PH circulation.