Regulation of vasopressin receptors in deoxycorticosterone acetate-salt hypertension

Deborah Trinder, Paddy A. Phillips, John Risvanis, Jayne M. Stephenson, Colin I. Johnston

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Since arginine vasopressin may play a role in mineralocorticoid hypertension, we examined the effects of deoxycorticosterone acetate (DOCA)-salt on vasopressin V1 and V2 receptor binding and their second messengers, inositol phosphate and adenylate cyclase, respectively, in liver and kidney to determine whether altered vasopressin receptor binding is pathogenetic in mineralocorticoid hypertension. The mean arterial blood pressure of mineralocorticoid (DOCA-salt)-treated rats (163±1 mm Hg) was increased compared with control salt-treated rats (salt) (122±1 mm Hg) and water-treated rats (120±1 mm Hg; p<0.001). Mineralocorticoid treatment also increased plasma sodium, osmolality, and vasopressin concentration (p<0.001). In the hypertensive animals, there was a reduction in hepatic V1 (DOCA-salt, 91±12; salt, 132±13; and water, 145±13 fmol/mg protein; p<0.05) and renal V2 receptor binding density (DOCA-salt, 53±5; salt, 93±9; and water, 95±9 fmol/mg protein; p<0.01), although receptor affinities remained unaltered. In contrast, the density of renal V1 receptors was increased by mineralocorticoid treatment (DOCA-salt, 24±2; salt, 16±2; water, 18±1 fmol/mg protein; p<0.05), although the affinity was unchanged. Downregulation of V2 receptors was associated with a decrease in maximum cyclic adenosine monophosphate levels (DOCA-salt, 19±4; salt, 49±6; water, 53±9 pmol · mg protein-1 · 10 min-1; p<0.05), whereas changes in V1 receptor levels were not associated with changes in maximum inositol phosphate levels. Therefore, changes in plasma vasopressin levels rather than changes in vasopressin receptors and their maximum second messenger levels are more likely to play a role in the development of mineralocorticoid hypertension.

Original languageEnglish
Pages (from-to)569-574
Number of pages6
JournalHypertension
Volume20
Issue number4
DOIs
Publication statusPublished - Oct 1992
Externally publishedYes

Keywords

  • Deoxycorticosterone
  • Hypertension, mineralocorticoid
  • Vasopressins

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