Effects of camp dependent protein kinase and guanylate cyclase
inhibition on intestinal microvascular responses to norepinephrine in
chronic portal hypertension.
Wu, Zhi-Yong, and Joseph N. Benoit.
DEPARTMENT OF PHYSIOLOGY, UNIVERSITY OF SOUTH ALABAMA COLLEGE OF
MEDICINE, MOBILE, ALABAMA 36688 AND DEPARTMENT OF PHYSIOLOGY AND
BIOPHYSICS, LOUISIANA STATE UNIVERSITY MEDICAL CENTER, SHREVEPORT,
LOUISIANA 71130
APStracts 3:0225G, 1996.
The purpose of the present study was to determine whether selective
blockade of cAMP or cGMP mediated events modulated norepinephrine
responses in intestinal microvessels of normal and portal
hypertensive rats. Vascular norepinephrine responses were evaluated
before and after inhibition of cAMP dependent kinase with Rp
-adenosine-3'-5'-cyclic monophosphothioate (Rp-cAMPs) or guanylate
cyclase with Ly-83583. Male Sprague-Dawley rats were divided into two
groups: portal hypertension by portal vein stenosis and normal
controls. The small intestine was prepared for microcirculatory
studies. Arteriolar diameter and erythrocyte velocity were monitored,
microvascular flow was calculated from velocity and diameter data.
The preparation was challenged with incremental concentrations of
norepinephrine before and after addition of Rp-cAMPs (50 [mu]M) or
LY-83583 (30 [mu]M). Arteriolar diameter and blood flow were
significantly elevated in portal hypertensive rats; norepinephrine
responses were significantly depressed. LY-83583 did not alter
arteriolar diameter, blood flow or norepinephrine responsiveness in
normal or portal hypertensive rats. Rp-cAMPs did not affect
arteriolar diameter, blood flow or norepinephrine responsiveness in
normal rats. However in portal hypertensive rats, Rp-cAMPs reduced
blood flow by nearly equal to 20% (p < 0.05) and completely
restored vascular norepinephrine responses to normal. The results
indicate that cAMP but not cGMP dependent events are primarily
responsible for the loss of microvascular norepinephrine
responsiveness in portal hypertensive intestine.
Received 5 September 1995; accepted in final form 22 October
1996.
APS Manuscript Number G391-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996