Role of the adventitia in the cyclic GMP-mediated relaxant effect of N-hydroxy-L-arginine in rat aorta.
N(omega)-hydroxy-L-arginine (L-NOHA), the stable intermediate of the nitric oxide synthase (NOS)-catalyzed reaction, can induce NO/cyclic GMP-dependent relaxation in the rat aorta, in an endothelium- and NOS-independent manner. In this study, the role of the adventitia in the endothelium-independent effect of L-NOHA was investigated. Despite a decrease in norepinephrine (NE)-induced precontraction, adventitia removal in the rat aorta did not markedly alter the relaxant effect of forskolin, S-nitroso-N-acetylpenicillamine or glyceryl trinitrate. In contrast, both inhibition of NE-induced contraction and relaxation of NE-precontracted rings produced by L-NOHA were diminished in the absence of adventitia. Moreover, exposure to L-NOHA significantly enhanced the cyclic GMP level in the media of the aorta with, but not without adventitia. These findings demonstrate the role of the adventitia in the L-NOHA-induced decrease in tone and increase in cyclic GMP in the endothelium-denuded rat aorta. They suggest that NO or an NO-related compound formed from L-NOHA in the adventitia may produce paracrine effects.
Pharmacologie et Physico-Chimie, UMR CNRS 7034, Université Louis Pasteur de Strasbourg, France.
Petra
P
Beranova
Christa
C
Schott
Karel
K
Chalupsky
Andrei L
AL
Kleschyov
Jean-Claude
JC
Stoclet
Bernard
B
Muller
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003238:Connective Tissue / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
C068309:N(omega)-hydroxyarginine; D001120:Arginine; D006152:Cyclic GMP; D009638:Norepinephrine