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Erik N.T.P. Bakker, Pieter Sipkema, Permissive effect of nitric oxide in arachidonic acid induced dilation in isolated rat arterioles, Cardiovascular Research, Volume 38, Issue 3, June 1998, Pages 782–787, https://doi.org/10.1016/S0008-6363(98)00046-7
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Abstract
Objective: Prostaglandins and nitric oxide play an important role in the regulation of arteriolar tone. l-Arginine analogues inhibit nitric oxide formation, but may also inhibit arachidonic-acid induced dilation. Nitric oxide was found to stimulate cyclooxygenase activity in cultured endothelial cells. Therefore, we hypothesized that the non-specific inhibition of prostaglandin-related dilation by l-arginine analogues is a consequence of the absence of nitric oxide. Methods: To test this hypothesis, arteriolar segments from rat cremaster muscle were studied in a pressure myograph at 75 mmHg. Segments developed spontaneous tone, the diameter reduced from 179±3 to 98±3 μm (n=41). In this condition, responses to exogenous arachidonic acid (1 μM) were recorded and compared with responses after addition of l-NNA, and addition of either SNAP, nitroprusside or 8-Br-cGMP in the presence of l-NNA. Results: Inhibition of basal nitric oxide production with l-NNA (0.1 mM) reduced arachidonic acid-induced dilation (from 52±9 to 31±6 μm). In the presence of l-NNA, responses to arachidonic acid were augmented when exogenous nitric oxide was also present (SNAP, 31±6 μm vs. 75±5 μm; nitroprusside, 31±8 μm vs. 42±7 μm). Responses were not augmented with the second messenger of nitric oxide-mediated dilation 8-Br-cGMP (37±9 μm vs. 32±9 μm). Conclusions: These results indicate that nitric oxide directly increases arachidonic acid-induced dilation. Thus, the non-specific effect of l-arginine analogues can be explained by a permissive effect of nitric oxide on endothelial arachidonic acid metabolism.
