title: Vascular contractile reactivity in hypotension due to reduced renal reabsorption of Na+and restricted dietary Na.
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.
authors.affiliation: Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA.
authors.forename: Saeed
authors.initials: S
authors.lastname: Alshahrani
authors.affiliation: Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA. robert.rapoport@uc.edu.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Rapoport
authors.affiliation: Research Service, Veterans Affairs Medical Center, Cincinnati, OH, 45220, USA.|Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA.
authors.forename: Manoocher
authors.initials: M
authors.lastname: Soleimani
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics / Q000378:metabolism; D001011:Aorta / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D001794:Blood Pressure; D004039:Diet, Sodium-Restricted; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D007022:Hypotension / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D018345:Mice, Knockout; D010641:Phenotype; D065608:Renal Reabsorption; D012982:Sodium, Dietary / Q000378:metabolism*; D064486:Solute Carrier Family 12, Member 3 / Q000235:genetics / Q000378:metabolism; D000076988:Sulfate Transporters; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D027321:Anion Transport Proteins; C578875:Slc12a3 protein, mouse; C494849:Slc26a4 protein, mouse; D012982:Sodium, Dietary; D064486:Solute Carrier Family 12, Member 3; D000076988:Sulfate Transporters; D014662:Vasoconstrictor Agents
keywords: Aorta; Contraction; Hypotension; Intravascular volume depletion; Knockout; Na+ reabsorption; Na-Cl cotransporter; Pendrin; Renal