Abstract
Reduced renal Na+ reabsorption along with restricted dietary Na+ depletes intravascular plasma volume which can then result in hypotension. Whether hypotension occurs and the magnitude of hypotension depends in part on compensatory angiotensin II-mediated increased vascular resistance. We investigated whether the ability of vascular resistance to mitigate the hypotension was compromised by decreased contractile reactivity. In vitro reactivity was investigated in aorta from mouse models of reduced renal Na+ reabsorption and restricted dietary Na+ associated with considerable hypotension and renin-angiotensin system activation: (1) the Na+-Cl−-Co-transporter (NCC) knockout (KO) with Na+ restricted diet (0.1%, 2 weeks) and (2) the relatively more severe pendrin (apical chloride/bicarbonate exchanger) and NCC double KO. Contractile sensitivity to KCl, phenylephrine, and/or U46619 remained unaltered in aorta from both models. Maximal KCl and phenylephrine contraction expressed as force/aorta length from NCC KO with Na+-restricted diet remained unaltered, while in pendrin/NCC double KO were reduced to 49 and 64%, respectively. Wet weight of aorta from NCC KO with Na+-restricted diet remained unaltered, while pendrin/NCC double KO was reduced to 67%, consistent with decreased medial width determined with Verhoeff-Van Gieson stain. These findings suggest that hypotension associated with severe intravascular volume depletion, as the result of decreased renal Na+ reabsorption, may in part be due to decreased contractile reactivity as a consequence of reduced vascular hypertrophy.
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Acknowledgements
This study was supported by a Merit Review award from the Department of Veterans Affairs, funds from the Center on Genetics of Transport and Epithelial Biology at the University of Cincinnati, and grants from the Dialysis Clinic, Inc. (DCI) and US Renal Care (MS) and a predoctoral scholarship from Jazan University, Saudi Arabia (SA). We thank Dr. David Witte (Department Pathology, Cincinnati Children’s Hospital Medical Center) for his suggestions.
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All procedures were approved by the Institutional Animal Care and Use Committee of the University of Cincinnati and were performed in accordance with the Guide for the Care and Use of Laboratory Animals of the National Research Council USA.
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Saeed Alshahrani and Robert M. Rapoport are first authors
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Alshahrani, S., Rapoport, R.M. & Soleimani, M. Vascular contractile reactivity in hypotension due to reduced renal reabsorption of Na+ and restricted dietary Na+ . Naunyn-Schmiedeberg's Arch Pharmacol 390, 321–326 (2017). https://doi.org/10.1007/s00210-017-1340-0
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DOI: https://doi.org/10.1007/s00210-017-1340-0