Role of local vasoconstrictors in diving performance of two pinniped species
Authors: Cupani Sebastiano , Hindle Allyson G 
Published: May 2024

Diving mammals extend submergence time through bradycardia and reduced peripheral perfusion to certain tissues. Thus, local blood flow regulation under hypoxia may be an essential physiological strategy that fine-tunes metabolic expenditures during breath-hold. We focused on a potent local vasoconstrictor, Endothelin-1 (ET1) and its receptors ETR-A and ETR-B, to determine their potential role in mammalian diving. We hypothesized that less perfused organs (kidney) would have higher signatures of local vasoconstriction (i.e. higher ET1 and receptors), compared to organs known to have higher relative perfusion underwater (heart/left ventricle). Additionally, we compared pinniped species with higher (Weddell seal) and lower (California sea lion) relative dive capabilities. Differences in mRNA expression of vasoconstrictive elements were assessed by 2-way ANOVA to compare tissue and species. In adult animals (n=7 both species) there were significant differences in expression of ET1 between species (F1,16=9.2, p=0.08) and tissues (F1,16=18.4, p=0.0006), with sea lions having consistently higher levels of ET1. ET1 expression was highest in the kidney, with sea lion kidney expressing 25x more ET1 mRNA than heart (posthoc p=0.0007). The expression ratio of ET A and B receptors also differed across tissue (F1,16=19.83 p=0.0004) with B/A highest in the kidney in both species. This is counter to expectations that submergence capability would relate to vasoconstriction potential across species, but supports the hypothesis that within a species, the less-perfused kidney should demonstrate higher potential for local vasoconstriction compared to the heart. Relative expression of ET receptors between tissues also runs counter to our hypothesis. In both divers, the heart expresses relatively more ETR-A, which has a critical role in vasoconstrictive signaling. On the other hand, ETR-B can signal for either vasoconstriction or vasodilation depending on its location within the endothelium or smooth muscle. Kidney in both species expresses relatively more ETR-B, indicating potential for nuanced vasoregulatory control through the endothelin pathway in this tissue. Receptor localization will be determined by immuno-staining to investigate functional differences between tissues. We also investigated the development of diving by comparing the same biomarkers in adults versus pups (n=10 seals, n=3 sea lions) using a separate 2-way ANOVA for each species. We expected that signatures of vasoregulatory potential would be less evident in the novice diving pups. Concordantly, ET1 is lower in sea lion pups than adults (F1,12=5.097, p=0.043); ET1 mRNA is 23x lower in the pup kidney compared to adult (posthoc p=0.02). Receptor expression followed the same patterns in both species, with the highest expression of ETR-A noted in the pup heart, indicating high vasoconstrictive potential in pups, but through tissue specific mechanisms. These results point to differences in the control of local vasoconstriction that occur with development and highlight the physiological components essential to the development of diving. Funding by NSF #2020706. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.