{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T22:49:54Z","timestamp":1762642194534,"version":"3.37.3"},"reference-count":63,"publisher":"American Physiological Society","issue":"6","funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation (NSF)","doi-asserted-by":"publisher","award":["1443554"],"award-info":[{"award-number":["1443554"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["U54 HG003067-08"],"award-info":[{"award-number":["U54 HG003067-08"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2019,6,1]]},"abstract":"<jats:p>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\u2013soluble 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\u2009\u00b1\u20093.7 pmol\u00b7mg protein<jats:sup>\u22121<\/jats:sup>\u00b7min<jats:sup>\u22121<\/jats:sup>) than the lungs of dogs (\u221280\u2009\u00b1\u2009144 pmol\u00b7mg protein<jats:sup>\u22121<\/jats:sup>\u00b7min<jats:sup>\u22121<\/jats:sup>less than seals), sheep (\u2212472\u2009\u00b1\u200996), rats (\u2212664\u2009\u00b1\u2009104) or mice (\u22121,160\u2009\u00b1\u2009104, P &lt; 0.0001). Amino acid sequences of the GC enzyme \u03b1-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.<\/jats:p>","DOI":"10.1152\/ajpregu.00283.2018","type":"journal-article","created":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T17:49:09Z","timestamp":1553104149000},"page":"R704-R715","source":"Crossref","is-referenced-by-count":13,"title":["Low guanylyl cyclase activity in Weddell seals: implications for peripheral vasoconstriction and perfusion of the brain during diving"],"prefix":"10.1152","volume":"316","author":[{"given":"Allyson G.","family":"Hindle","sequence":"first","affiliation":[{"name":"Anesthesia Center for Critical Care Medicine, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaitlin N.","family":"Allen","sequence":"additional","affiliation":[{"name":"Anesthesia Center for Critical Care Medicine, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annabelle J.","family":"Batten","sequence":"additional","affiliation":[{"name":"Anesthesia Center for Critical Care Medicine, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis A.","family":"H\u00fcckst\u00e4dt","sequence":"additional","affiliation":[{"name":"Department of Ecology and Evolutionary Biology, University of California, Santa Cruz, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Turner-Maier","sequence":"additional","affiliation":[{"name":"Vertebrate Genome Biology, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. 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