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Low guanylyl cyclase activity in Weddell seals: implications for peripheral vasoconstriction and perfusion of the brain during diving
Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA;Harvard Med Sch, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA;Harvard Med Sch, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA;Harvard Med Sch, Boston, MA 02115 USA.
Univ Calif Santa Cruz, Dept Ecol & Evolutionary Biol, Santa Cruz, CA 95064 USA.
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2019 (English)In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 316, no 6, p. R704-R715Article in journal (Refereed) Published
Abstract [en]

Nitric oxide (NO) is a potent vasodilator, which improves perfusion and oxygen delivery during tissue hypoxia in terrestrial animals. The vertebrate dive response involves vasoconstriction in select tissues. which persists despite profound hypoxia. Using tissues collected from Weddell seals at necropsy, we investigated whether vasoconstriction is aided by downregulation of local hypoxia signaling mechanisms. We focused on NO-soluble guanylyl cyclasc (GC)-cGMP signaling, a well-known vasodilatory transduction pathway. Seals have a lower GC protein abundance. activity, and capacity to respond to NO stimulation than do terrestrial mammals. In seal lung homogenates, GC produced less cGMP (20.1 +/- 3.7 pmol.mg protein(-1).min(-1)) than the lungs of dogs (-80 +/- 144 pmol.mg protein(-1).min(-1) less than seals), sheep (-472 +/- 96), rats (-664 +/- 104) or mice ( -1,160 +/- 104, P < 0.0001). Amino acid sequences of the GC enzyme alpha-subunits differed between seals and terrestrial mammals, potentially affecting their structure and function. Vasoconstriction in diving Weddell seals is not consistent across tissues; perfusion is maintained in the brain and heart but decreased in other organs such as the kidney. A NO donor increased median GC activity 49.5-fold in the seal brain but only 27.4-fold in the kidney. consistent with the priority of cerebral perfusion during diving. Nos3 expression was high in the seal brain, which could improve NO production and vasodilatory potential. Conversely, Pde5a expression was high in the seal renal artery, which may increase cGMP breakdown and vasoconstriction in the kidney. Taken together, the results of this study suggest that alterations in the NO-cGMP pathway facilitate the diving response.

Place, publisher, year, edition, pages
AMER PHYSIOLOGICAL SOC , 2019. Vol. 316, no 6, p. R704-R715
Keywords [en]
dive response, NO-cGMP signaling, pinniped, soluble guanylate cyclase
National Category
Physiology
Identifiers
URN: urn:nbn:se:uu:diva-386431DOI: 10.1152/ajpregu.00283.2018ISI: 000469020400002PubMedID: 30892912OAI: oai:DiVA.org:uu-386431DiVA, id: diva2:1330945
Available from: 2019-06-26 Created: 2019-06-26 Last updated: 2019-06-26Bibliographically approved

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Lindblad-Toh, Kerstin

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Department of Medical Biochemistry and MicrobiologyScience for Life Laboratory, SciLifeLab
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