© 2001 American Heart Association, Inc.
Vascular Biology |
cAMP Signal Transduction Cascade, a Novel Pathway for the Regulation of Endothelial Nitric Oxide Production in Coronary Blood Vessels
From the Department of Physiology, New York Medical College, Valhalla, NY.
Correspondence to Thomas H. Hintze, PhD, Professor, Department of Physiology, New York Medical College, Valhalla, NY 10595. E-mail Thomas_Hintze{at}nymc.edu
Abstract—The
aim of this study was to determine whether cAMP signal transduction
plays a role in the regulation of endothelial nitric
oxide (NO) production. Canine coronary blood vessels
were isolated, and nitrite, the hydration product of NO, from these
vessels was quantified by using the Griess reaction. Forskolin
(10-4 mol/L), 8-bromo-cAMP
(10-2 mol/L), or isoproterenol
(10-4 mol/L) significantly increased
nitrite release to 168±10, 162±13, or 149±13 pmol/mg, respectively,
from isolated coronary microvessels (all
P<0.05; control, 86±3
pmol/mg). Adrenomedullin and calcitonin gene–related peptide (CGRP),
both potent vasodilator peptides, also increased coronary
microvascular nitrite production.
N
-nitro-L-arginine
methyl ester, a competitive inhibitor of NO synthase, or
Rp-cAMP, a protein kinase A inhibitor, markedly blocked the
nitrite release induced by these agents. Forskolin and adrenomedullin
also potentiated coronary NO production induced by
bradykinin. In large coronary arteries, removal of the
endothelium eliminated nitrite production to
both forskolin and acetylcholine. Our data demonstrate that stimulation
of cAMP signal transduction can substantially increase coronary
NO production, indicating that there is a cAMP-mediated,
endothelial NO–forming system in coronary
blood vessels. Because the cAMP signal cascade can be activated
by CGRP or adrenomedullin and enhance kinin-mediated nitrite
production, the cAMP-NO pathway may play an important role in
the regulation of cardiovascular function.
Key Words: cAMP • nitric oxide • endothelium • protein kinase B • coronary blood vessels
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