title: Hypernatremia-induced vasopressin secretion is not altered in TRPV1-/- rats.
abstract: Changes in osmolality or extracellular NaCl concentrations are detected by specialized neurons in the hypothalamus to increase vasopressin (VP) and stimulate thirst. Recent in vitro evidence suggests this process is mediated by an NH2-terminal variant of the transient receptor potential vanilloid type 1 (TRPV1) channel expressed by osmosensitive neurons of the lamina terminalis and vasopressinergic neurons of the supraoptic nucleus. The present study tested this hypothesis in vivo by analysis of plasma VP levels during acute hypernatremia in awake control and TRPV1(-/-) rats. TRPV1(-/-) rats were produced by a Zinc-finger-nuclease 2-bp deletion in exon 13. Intravenous injection of the TRPV1 agonist capsaicin produced hypotension and bradycardia in control rats, but this response was absent in TRPV1(-/-) rats. Infusion of 2 M NaCl (1 ml/h iv) increased plasma osmolality, electrolytes, and VP levels in both control and TRPV1(-/-) rats. However, plasma VP levels did not differ between strains at any time. Furthermore, a linear regression between plasma VP versus osmolality revealed a significant correlation in both control and TRPV1(-/-) rats, but the slope of the regression lines was not attenuated in TRPV1(-/-) versus control rats. Hypotension produced by intravenous injection of minoxidil decreased blood pressure and increased plasma VP levels similarly in both groups. Finally, both treatments stimulated thirst; however, cumulative water intakes in response to hypernatremia or hypotension were not different between control and TRPV1(-/-) rats. These findings suggest that TRPV1 channels are not necessary for VP secretion and thirst stimulated by hypernatremia.
authors.affiliation: Department of Neural & Behavioral Sciences, Penn State College of Medicine, Hershey, Pennsylvania.
authors.forename: Andrew Blake
authors.initials: AB
authors.lastname: Tucker
authors.affiliation: Department of Neural & Behavioral Sciences, Penn State College of Medicine, Hershey, Pennsylvania sstocker@hmc.psu.edu.
authors.forename: Sean D
authors.initials: SD
authors.lastname: Stocker
mesh_terms: D000818:Animals; D004326:Drinking; D006955:Hypernatremia / Q000378:metabolism*; D008297:Male; D018345:Mice, Knockout; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D013894:Thirst; D014667:Vasopressins / Q000097:blood* / Q000378:metabolism; D014882:Water-Electrolyte Balance
chemical_list: D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D014667:Vasopressins
keywords: antidiuretic hormone; hypernatremia; osmoreceptor; thirst