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Low guanylyl cyclase activity in Weddell seals : implications for peripheral vasoconstriction and perfusion of the brain during diving

Hindle, Allyson G. (författare)
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
Allen, Kaitlin N. (författare)
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
Batten, Annabelle J. (författare)
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
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Huckastadt, Luis A. (författare)
Univ Calif Santa Cruz, Dept Ecol & Evolutionary Biol, Santa Cruz, CA 95064 USA
Turner-Maier, Jason (författare)
Brd Inst Massachusetts Inst Technol & Harvard Uni, Vertebrate Genome Biol, Cambridge, MA USA
Schulberg, S. Anne (författare)
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
Johnson, Jeremy (författare)
Brd Inst Massachusetts Inst Technol & Harvard Uni, Vertebrate Genome Biol, Cambridge, MA USA
Karlsson, Elinor (författare)
Brd Inst Massachusetts Inst Technol & Harvard Uni, Vertebrate Genome Biol, Cambridge, MA USA
Lindblad-Toh, Kerstin (författare)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Brd Inst Massachusetts Inst Technol & Harvard Uni, Vertebrate Genome Biol, Cambridge, MA USA
Costa, Daniel P. (författare)
Univ Calif Santa Cruz, Dept Ecol & Evolutionary Biol, Santa Cruz, CA 95064 USA
Bloch, Donald B. (författare)
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, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA
Zapol, Warren M. (författare)
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
Buys, Emmanuel S. (författare)
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
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 (creator_code:org_t)
AMER PHYSIOLOGICAL SOC, 2019
2019
Engelska.
Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : AMER PHYSIOLOGICAL SOC. - 0363-6119 .- 1522-1490. ; 316:6, s. R704-R715
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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.

Ämnesord

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)

Nyckelord

dive response
NO-cGMP signaling
pinniped
soluble guanylate cyclase

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