Role of nitric oxide mechanism in the cardiovascular effects of
diaspirin crosslinked hemoglobin in anesthetized rats.
Sharma, Avadhesh C., Govind Singh, and Anil Gulati.
Department of Pharmaceutics and Pharmacodynamics (m/c 865), The
University of Illinois at Chicago, 833 South Wood Street, Chicago, IL
60612
APStracts 2:0170H, 1995.
Sharma, Avadhesh C., Govind Singh, and Anil Gulati. Role of nitric
oxide mechanism in the cardiovascular effects of diaspirin
crosslinked hemoglobin in anesthetized rats. Am. J. Physiol. 000
(Heart Circulatory Physiol. 0): H000-H000, 1995. The role of nitric
oxide (NO) in the cardiovascular actions of diaspirin crosslinked
hemoglobin (DCLHb) was studied in anesthetized rats. The regional
circulatory and systemic hemodynamic effects of DCLHb (400 mg/kg iv)
were studied using a radioactive microsphere technique in control
(untreated) and l-arginine (NO precursor) pretreated rats. DCLHb
produced a significant increase in blood pressure (75%), cardiac
output (42%), stroke volume (36%) and total peripheral resistance
(45%) without affecting heart rate, when administered to control
rats. l-arginine pretreatment significantly attenuated DCLHb-induced
systemic hemodynamic effects. DCLHb induced increase in blood flow to
the skin and spleen was completely and to the heart was partially
blocked by l-arginine pretreatment suggesting that cardiovascular
actions induced by DCLHb could be antagonized by NO precursor, l
-arginine. NO synthase (NOS) inhibitor, l-NAME (NG-nitro-l-arginine
methyl ester), produced significant increases in regional vascular
resistance leading to a decrease in blood flow to all the organs
excepting heart, where an increase in blood flow and decrease in
vascular resistance was observed. DCLHb when administered in l-NAME
pretreated rats, accentuated the decrease in blood flow to the GIT,
spleen, mesentery and pancreas, skin and musculoskeletal system.
These studies provide evidence that NO precursor l-arginine can
attenuate the effects of DCLHb, and DCLHb can potentiate the effect
of NOS inhibitor, l-NAME. The role of NO in the mechanism of action
of DCLHb was further studied by estimating plasma cGMP in control,
DCLHb treated, l-NAME treated and l-NAME followed by DCLHb treated
rats. DCLHb and l-NAME significantly decreased the concentration of
circulating cGMP in the blood plasma. l-NAME pretreatment potentiated
DCLHb-induced decrease in cGMP levels. Since the formation of cGMP is
stimulated by NO, these studies provide additional evidence for the
involvement of NO in the mechanism of action of DCLHb. It is
concluded that NO plays an important role in the cardiovascular
effects of DCLHb.
Received 28 December 1993; accepted in final form 5 April 1995.
APS Manuscript Number H1139-3.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 2 May 1995.