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 activity during hypoxia was studied in anesthetized pigs (n = 21). Hypoxia (fractional concentration of O2 in inspired air = 0.1) increased pulmonary arterial pressure and decreased arterial blood pressure and peripheral vascular resistance. Renal sympathetic nerve activity (RSNA) was moderately increased during hypoxia but decreased instantaneously on reoxygenation. Blockade of NO synthesis by NG-nitro-L-arginine (L-NNA, 0.3 mmol/l) administered to the ventral surface of the medulla oblongata (VLM) significantly enhanced RSNA increases induced by hypoxia and abolished the RSNA response to reoxygenation. Furthermore, L-NNA significantly reduced peripheral hypoxic vasodilation but did not affect pulmonary vasoconstriction. The inactive enantiomer D-NNA had no measurable effects at the same concentration. Actions of L-NNA were effectively counteracted by the NO donor S-nitroso-N-acetyl-penicillamine (0.1 mmol/l). Deafferentiation (carotid sinus and vagal nerves cut) abolished sympathetic responses to hypoxia and their modulation by NO. The results suggest that activation of peripheral chemoreceptors induces NO release in the VLM that buffers sympathoexcitation during hypoxia and contributes to sympathoinhibition during reoxygenation.
I. Physiologisches Institut, Universität Heidelberg, D-69120 Heidelberg, Germany.
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Zanzinger
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Czachurski
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Seller
D000818:Animals; D001794:Blood Pressure; D002302:Cardiac Output; D006339:Heart Rate; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology*; D007263:Infusions, Parenteral; D007668:Kidney / Q000294:innervation; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine / Q000008:administration & dosage / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011651:Pulmonary Artery / Q000502:physiology / Q000503:physiopathology; D026423:S-Nitroso-N-Acetylpenicillamine; D013238:Stereotaxic Techniques; D013552:Swine; D013564:Sympathetic Nervous System / Q000502:physiology / Q000503:physiopathology*; D014655:Vascular Resistance
D019335:Nitroarginine; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D010396:Penicillamine