NONRECEPTOR-MEDIATED INTESTINAL VASOCONSTRICTION IN PORTAL HYPERTENSIVE RATS

Previous studies have demonstrated that receptor-mediated vasoconstric tion is impaired in chronic portal hypertension (PH). Furthermore, it has been suggested that altered vasoconstrictor effectiveness in chron ic PH is due to a defect in the intracellular events associated with s mooth muscle activation and not to impaired coupling of vasoconstricto rs with vascular smooth muscle receptors. The present study was design ed 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 prot eins, KCl-induced depolarization, caffeine-induced release of intracel lular 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 studie s and transferred to a video microscope. First-order arteriolar (1A) d iameter and red cell velocity were measured on-line. Blood flow was ca lculated from the product of velocity and microvessel cross-sectional area. After a control period, the microvasculature was exposed to a so lution containing aluminum chloride plus sodium fluoride, potassium ch loride, caffeine, or l-indolactam. Maximal decreases in arteriolar dia meter produced by aluminum fluoride, KCl, caffeine, and l-indolactam w ere significantly greater in Norm rats when compared with PH rats. Cha nges in arteriolar blood flow were also larger in Norm than in PH rats . The results of the present study provide the first direct evidence o f an impaired response to second-messenger activation in the PH circul ation.