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

• DOI: 10.1152/ajpregu.00283.2018
• Publication Date: 2019-03-20T17:49:09Z
• Authors: Allyson G. Hindle; Kaitlin N. Allen; Annabelle J. Batten; Luis A. Hückstädt; Jason Turner-Maier; S. Anne Schulberg; Jeremy Johnson; Elinor Karlsson; Kerstin Lindblad-Toh; Daniel P. Costa; Donald B. Bloch; Warren M. Zapol; Emmanuel S. Buys
• Keywords: Soluble guanylyl cyclase; Hypoxia; Hypoxic pulmonary vasoconstriction

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