MINIREVIEW
Inducible NO Synthase Activity in Blood Vessels and Heart:
New Insight into Cell Origin and Consequences
B. MULLER, A. L. KLESCHYOV,
K. GYORGY, J.-C. STOCLET
Pharmacologie et Physico-Chimie des Interactions Cellulaires
et Moléculaires UMR CNRS 7034, Université Louis Pasteur de
Strasbourg, Faculté de Pharmacie, Illkirch, France
Received July
30, 1999
Accepted September 21, 1999
Summary
Induction of the inducible form of nitric oxide synthase (iNOS)
in the vascular and cardiac tissue by several inflammatory
stimuli may result in the production of large amounts of nitric
oxide (NO) for a sustained period. Recent data obtained in the
rat aorta in which iNOS was induced by lipopolysaccharide (LPS)
have demonstrated that adventitial cells represent the main site
of NO production. Adventitial-derived NO can exert an immediate
down-regulatory effect on smooth muscle contraction (via
activation of the cyclic GMP pathway) but may also initiate
longer lasting effects through the formation of NO stores within
the medial layer. One candidate for such NO stores are
dinitrosyl non-heme iron complexes. Low molecular weight thiols
interact with preformed NO stores and promote vasorelaxation by
a cyclic GMP-independent mechanism involving the activation of
potassium channels. In the heart, the induction of iNOS is
involved in delayed protection against
ischemia-reperfusion-induced functional damages. Recent data
obtained with monophosphoryl lipid A, a non-toxin derivative of
LPS, strongly suggest that iNOS-derived NO in the rat heart does
not act as an immediate mediator of the cardioprotection but
rather as a trigger of long-term protective mechanisms. Thus,
the present data reveal the important role of adventitial cells
as a site of iNOS expression and activity in intact blood
vessels. The induction of adaptive mechanisms in the heart and
the formation of releasable NO stores in blood vessels are
examples of long-term consequences of iNOS induction. These new
information are relevant for a better understanding of the
circumstances in which NO overproduction by iNOS may play either
a beneficial or deleterious role in these tissues.
Key
words
Blood vessels · Cardioprotection · Dinitrosyl-iron complexes · Inducible NO synthase ·
Nitric oxide stores
Reprint
requests
B. Muller, Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires,
UMR CNRS 7034, Université Louis Pasteur, Faculty of Pharmacy, BP 24, 67401 Illkirch,
Cedex, France. e-mail: bmuller@pharma.u-strasbg.fr
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