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This Article Full Text Full Text (PDF) All Versions of this Article: 293/6/L1463    most recent 00249.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by He, L. Articles by Fidone, S. Search for Related Content PubMed PubMed Citation Articles by He, L. Articles by Fidone, S.

Enhanced nitric oxide-mediated chemoreceptor inhibition and altered cyclic GMP signaling in rat carotid body following chronic hypoxia

Department of Physiology, University of Utah School of Medicine, Salt Lake City, Utah

Submitted 28 June 2007 ; accepted in final form 2 October 2007

Multiple studies have shown that chronic hypoxia (CH) elicits a time-dependent upregulation of carotid body chemoreceptor sensitivity in mammals. In the present study, we demonstrate that enhanced excitation is accompanied by a parallel increase of nitric oxide (NO)-dependent inhibition, which acts via a CH-induced modification of the normal mechanism in O₂-sensitive type I cells. The NO synthase inhibitor, N^G-nitro-L-arginine methyl ester (L-NAME), elicits a progressively larger increase in carotid sinus nerve (CSN) chemoreceptor activity following incremental increases in CH exposure lasting 1–16 days. The inhibitory effect of the NO donor, S-nitroso-N-acetyl-penicillamine (SNAP), on CSN activity is enhanced following CH. However, the activation of soluble guanylate cyclase (sGC) by SNAP, assessed via production of cGMP, is impaired, along with decreased expression of sGC mRNA transcript. Inhibition of hypoxia-evoked Ca²⁺ responses by SNAP is mediated via a cGMP/protein kinase G (PKG)-dependent mechanism in normal type I cells that is sensitive to the PKG inhibitor KT-5823, but following CH, inhibitory responses are minimally sensitive to PKG inhibition. The data are consistent with the hypothesis that CH hampers cGMP-mediated inhibition of type I cells in favor of an alternative mechanism.

chemoreceptor sensitivity