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

08:00 EDT 20th March 2019 | BioPortfolio

Summary of "Low guanylyl cyclase activity in Weddell seals: Implications for peripheral vasoconstriction and perfusion of the brain during diving."

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 down-regulation of local hypoxia signaling mechanisms. We focused on NO-soluble guanylyl cyclase (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•min) than the lungs of dogs (-80±144 pmol•mg protein•min less than seals), sheep (-472±96), rats (-664±104) or mice (-1160±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. An 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. Nos3expression was high in the seal brain, which could improve NO production and vasodilatory potential. Conversely, Pde5aexpression 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.


Journal Details

This article was published in the following journal.

Name: American journal of physiology. Regulatory, integrative and comparative physiology
ISSN: 1522-1490


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Compunds that bind to and activate GUANYLYL CYCLASE-C RECEPTORS.

Cell surface proteins that bind ATRIAL NATRIURETIC FACTOR with high affinity and trigger intracellular changes influencing the behavior of cells. They contain intrinsic guanylyl cyclase activity.

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A non-hydrolyzable analog of GTP, in which the oxygen atom bridging the beta to the gamma phosphate is replaced by a nitrogen atom. It binds tightly to G-protein in the presence of Mg2+. The nucleotide is a potent stimulator of adenylate cyclase.

A group comprised of several species of eared seals found in two genera, in the family Otariidae. In comparison to SEA LIONS, they have an especially dense wooly undercoat.

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