NITRIC-OXIDE IN THE VENTROLATERAL MEDULLA REGULATES SYMPATHETIC RESPONSES TO SYSTEMIC HYPOXIA IN PIGS

The role of nitric oxide (NO) in the regulation of sympathetic activit y during hypoxia was studied in anesthetized pigs (n = 21). Hypoxia (f ractional concentration of O-2 in inspired air = 0.1) increased pulmon ary arterial pressure and decreased arterial blood pressure and periph eral vascular resistance. Renal sympathetic nerve activity (RSNA) was moderately increased during hypoxia but decreased instantaneously on r eoxygenation. Blockade of NO synthesis by N-G-nitro-L-arginine (L-NNA, 0.3 mmol/l) administered to the ventral surface of the medulla oblong ata (VLM) significantly enhanced RSNA increases induced by hypoxia and abolished the RSNA response to reoxygenation. Furthermore, L-NNA sign ificantly reduced peripheral hypoxic vasodilation but did not affect p ulmonary vasoconstriction. The inactive enantiomer D-NNA had no measur able effects at the same concentration. Actions of L-NNA were effectiv ely counteracted by the NO donor S-nitroso-N-acetyl-penicillamine (0.1 mmol/l). Deafferentiation (carotid sinus and vagal nerves cut) abolis hed sympathetic responses to hypoxia and their modulation by NO. The r esults suggest that activation of peripheral chemoreceptors induces NO release in the VLM that buffers sympathoexcitation during hypoxia and contributes to sympathoinhibition during reoxygenation.