EFFECTS OF PROPRANOLOL ON INTESTINAL MICROCIRCULATION OF NORMAL AND PORTAL HYPERTENSIVE RATS

Background/Aims: The goal of the present study was to compare the effi cacy of locally and systemically administered propranolol in normal an d prehepatic portal hypertensive rats, and to test the hypothesis that beta-adrenoceptor blockade reduces intestinal arteriolar diameter by allowing unopposed alpha-adrenergic activity. Methods: The small intes tine was prepared for in vivo microcirculatory studies and transferred to an intravital microscope where arteriolar diameter and erythrocyte velocity were continuously monitored, First order arteriolar (1A) blo od flow was calculated from the product of mean velocity and microvess el cross-sectional area. In separate experiments, diameter responses o f 2A and 3A were monitored, Once steady-state conditions were achieved , the preparation was challenged by topically applied doses of propran olol (0.01-100.00 mu M) in the presence and absence of the alpha-recep tor antagonist, phentolamine. In a separate group of experiments, the effects of systemically administered propranolol (10 mg/kg body weight ) were evaluated before and after local alpha-adrenoceptor blockade. R esults: Propranolol produced significant vasoconstriction and decrease d blood flow in both normal and portal hypertensive rats. Portal hyper tensive arterioles exhibited an attenuated response to propranolol, Lo cal administration of phentolamine completely blocked the propranolol- induced diameter changes, Comparison of equivalent concentrations of l ocal and systemic propranolol indicated that both routes of administra tion were equally effective, Conclusion: The results of the present st udy suggest that the cardiovascular actions of propranolol are predomi nantly mediated through blockade of peripheral beta(2)-adrenoceptor.