Abstract
Experiments were designed to determine the role of the L-arginine pathway in endothelium-dependent relaxations to vasopressin. The effects of L- arginine analogues N(G)-nitro-L-arginine (L-NNA), N(G)-nitro-L-arginine methyl ester (L-NAME), and N(G)-monomethyl-L-arginine (L-NMMA) on basal and vasopressin-induced activity of nitric oxide synthase were studied in isolated canine basilar arteries. Rings with and without endothelium were suspended for isometric tension recording in Krebs-Ringer bicarbonate solution bubbled with 94% O2-6% CO2 (37°C, pH 7.4). Radioimmunoassay was used to determine the level of guanosine 3',5'-cyclic monophosphate (cGMP). All experiments were performed in the presence of indomethacin, a cyclooxygenase inhibitor. L-NAME and L-NMMA caused endothelium-dependent contractions and inhibited basal production of cGMP. In contrast, L-NNA did not affect basal tone or basal production of cGMP. L-Arginine analogues inhibited relaxations to vasopressin but did not affect relaxations to a nitric oxide donor, molsidomine (SIN-1). The effects of L-NNA, L-NAME, and L- NMMA were reversed in the presence of L-arginine. The relaxations to vasopressin were associated with an increase of cGMP levels in the arterial wall. This effect of vasopressin was inhibited in the presence of L-NNA. These studies suggest that the relaxations to vasopressin are mediated by activation of the endothelial L-arginine pathway, leading to increased production of nitric oxide, with subsequent activation of guanylate cyclase in smooth muscle cells. In canine basilar artery, L-NAME and L-NMMA are nonselective inhibitors of both basal and stimulated production of nitric oxide, whereas L-NNA selectively inhibits vasopressin-induced activation of the L-arginine pathway.
Original language | English (US) |
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Pages (from-to) | H413-H418 |
Journal | American Journal of Physiology - Heart and Circulatory Physiology |
Volume | 264 |
Issue number | 2 33-2 |
DOIs | |
State | Published - 1993 |
Keywords
- cerebral arteries
- endothelium- derived relaxing factor
- guanosine 3',5'-cyclic monophosphate
- nitric oxide
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)