Chronic hypoxia selectively augments endothelium-dependent
pulmonary arterial vasodilation.
Resta, Thomas C., and Benjimen R. Walker.
Department of Physiology, University of New Mexico, School of
Medicine, Albuquerque, New Mexico 87131
APStracts 2:0339H, 1995.
A Previous study from our laboratory has demonstrated enhanced
arterial dilation to the endothelium-derived nitric oxide (EDNO)
-dependent pulmonary vasodilator arginine vasopressin (AVP) in lungs
isolated from chronically hypoxic (CH) rats compared to lungs from
control animals. The present study examined 1) whether this change in
arterial reactivity is also observed with other agents that act via
stimulation of constitutive nitric oxide synthase (cNOS), 2) whether
arterial vascular smooth muscle reactivity to NO is enhanced by CH,
or 3) whether arterial vasodilation in lungs from CH rats is
augmented by release of other endothelium-derived dilators such as
endothelin (ET) or an endothelium-derived hyperpolarizing factor
(EDHF). We examined responses in U-46619 constricted, isolated
perfused lungs from control and CH rats to the receptor-mediated
EDNO-dependent dilators histamine and endothelin-1 (ET-1), the non
-receptor-mediated EDNO-dependent dilator ionomycin, and the NO donors
spermine NONOate and S-nitroso-N-acetylpenicillamine (SNAP).
Additional experiments examined responses to AVP in the presence of
the ET receptor antagonist PD145065 or the K+ channel blockers
glibenclamide or tetraethylammonium (TEA) in lungs from both groups.
Segmental resistances were assessed by double occlusion technique.
Total and arterial vasodilatory responses to histamine, ET-1 and
ionomycin were augmented in lungs from CH vs control rats over a
range of doses. However, no differences were observed in the
vasodilatory responses to spermine NONOate or SNAP between the two
groups. PD145065, glibenclamide, and TEA had no effect on responses
to AVP in lungs from either control or CH rats. We conclude that the
augmented pulmonary arterial dilation to EDNO-dependent vasodilators
that occurs with exposure to CH may involve changes in the activity
of cNOS within the pulmonary arterial vasculature.
Received 5 May 1995; accepted in final form 3 August 1995.
APS Manuscript Number H424-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.