Low Guanylyl Cyclase Activity in Weddell Seals: Implications for Peripheral Vasoconstriction and Perfusion of the Brain During Diving

Authors

Allyson G. Hindle, University of Nevada, Las VegasFollow
Kaitlin N. Allen, Massachusetts General Hospital and Harvard Medical School
Annabelle J. Batten, Massachusetts General Hospital and Harvard Medical School
Luis A. Hückstädt, University of California, Santa Cruz
Jason Turner-Maier, Broad Institute of Massachusetts Institute of Technology and Harvard University
S. Anne Schulberg, Massachusetts General Hospital and Harvard Medical School
Jeremy Johnson, Broad Institute of Massachusetts Institute of Technology and Harvard University
Elinor Karlsson, Broad Institute of Massachusetts Institute of Technology and Harvard University
Kerstin Lindblad-Toh, Broad Institute of Massachusetts Institute of Technology and Harvard University
Daniel P. Costa, University of California, Santa Cruz
Donald B. Bloch, Massachusetts General Hospital and Harvard Medical School
Warren M. Zapol, Massachusetts General Hospital and Harvard Medical School
Emmanuel S. Buys, Massachusetts General Hospital and Harvard Medical School

Document Type

Article

Publication Date

5-21-2019

Publication Title

American journal of physiology. Regulatory, integrative and comparative physiology

Volume

316

Issue

6

First page number:

R704

Last page number:

R715

Abstract

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 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−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 α-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.

Keywords

Dive response; NO-CGMP signaling; Pinniped; Soluble guanylate cyclase

Disciplines

Life Sciences | Marine Biology

Language

English

Repository Citation

Hindle, A. G., Allen, K. N., Batten, A. J., Hückstädt, L. A., Turner-Maier, J., Schulberg, S. A., Johnson, J., Karlsson, E., Lindblad-Toh, K., Costa, D. P., Bloch, D. B., Zapol, W. M., Buys, E. S. (2019). Low Guanylyl Cyclase Activity in Weddell Seals: Implications for Peripheral Vasoconstriction and Perfusion of the Brain During Diving. American journal of physiology. Regulatory, integrative and comparative physiology, 316(6), R704-R715.
http://dx.doi.org/10.1152/ajpregu.00283.2018