ROLE OF NITRIC-OXIDE AND PROSTAGLANDINS IN THE REGULATION OF DIAPHRAGMATIC ARTERIOLAR TONE IN THE RAT

We evaluated by intravital microscopy in rats the relative importance of nitric oxide (NO) and prostaglandins in 1) the maintenance of basal diaphragmatic arteriolar tone and 2) the response of diaphragmatic arterioles to the endothelium-dependent vasodilator acetylcholine (ACh). One hundred two mechanically ventilated rats were studied. Separate applications of N omega-nitro-L-arginine (L-NNA) and mefenamic acid (MA), which are specific inhibitors of NO and prostaglandin synthesis, respectively, elicited a significant reduction in basal diaphragmatic arteriolar diameter. A dramatic potentiation of the effect of each inhibitor was observed when both agents were applied simultaneously. ACh application induced a significant and dose-dependent increase in arteriolar diameter that was not significantly modified by the separate application of L-NNA or MA. Conversely, the simultaneous administration of L-NNA. and MA almost completely prevented ACh-induced arteriolar dilatation. Dilatation in response to sodium nitroprusside was not significantly modified in the presence of both inhibitors. These results suggest that NO and prostaglandins act in concert to regulate basal diaphragmatic arteriolar tone and to mediate diaphragmatic arteriolar response to ACh.