NITRIC-OXIDE SYNTHASE ISOFORMS AND PERIPHERAL CHEMORECEPTOR STIMULATION IN CONSCIOUS RATS

To test the effect of nitric oxide synthase (NOS) blockade on the vent ilatory responses to carotid body chemoreceptor stimulation in freely behaving animals, chronically instrumented adult Sprague-Dawley rats r eceived increasing intravenous doses of sodium cyanide (NaCN; 0-300 mu g kg(-1)) before and after i.v. administration of either 100 mg kg(-1 ) N-nitro-L-arginine methyl ester (L-NAME ), a non-specific NOS blocke r, or 10 mg kg(-1) S-methyl-L-thiocitrulline (SMTC), a selective neuro nal NOS inhibitor. SMTC did not modify the NaCN dose-response curve. I n contrast, L-NAME significantly enhanced the ventilatory responses to NaCN. Western blots of equivalent amounts of protein from carotid bod y tissue homogenates revealed higher levels of endothelial NOS than of neuronal NOS. We conclude that endothelial NOS provides the major sou rce for NO within the carotid body, and exerts a down-regulatory effec t upon peripheral chemoreceptor responsivity.