Effects of propranolol on intestinal microcirculation of normal and portal hypertensive rats.
OBJECTIVE
The goal of the present study was to compare the efficacy of locally and systemically administered propranolol in normal and 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 intestine 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) blood flow was calculated from the product of mean velocity and microvessel cross-sectional area. In separate experiments, diameter responses of 2A and 3A were monitored. Once steady-state conditions were achieved, the preparation was challenged by topically applied doses of propranolol (0.01-100.00 microM) in the presence and absence of the alpha-receptor 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.


RESULTS
Propranolol produced significant vasoconstriction and decreased blood flow in both normal and portal hypertensive rats. Portal hypertensive arterioles exhibited an attenuated response to propranolol. Local administration of phentolamine completely blocked the propranolol-induced diameter changes. Comparison of equivalent concentrations of local and systemic propranolol indicated that both routes of administration were equally effective.


CONCLUSIONS
The results of the present study suggest that the cardiovascular actions of propranolol are predominantly mediated through blockade of peripheral beta 2-adrenoceptor.
Wu
Z Y
ZY
Department of Physiology & Biophysics Louisiana State University Medical Center Shreveport 71130-3932, USA.
Benoit
J N
JN
D000818:Animals; D004333:Drug Administration Routes; D006439:Hemodynamics; D006975:Hypertension, Portal / Q000188:drug therapy / Q000503:physiopathology*; D007422:Intestines / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010646:Phentolamine / Q000008:administration & dosage; D011433:Propranolol / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*
D011433:Propranolol; D010646:Phentolamine