Regulation of vasopressin receptors in deoxycorticosterone acetate-salt hypertension.
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 less than 0.001). Mineralocorticoid treatment also increased plasma sodium, osmolality, and vasopressin concentration (p less than 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 less than 0.05) and renal V2 receptor binding density (DOCA-salt, 53 +/- 5; salt, 93 +/- 9; and water, 95 +/- 9 fmol/mg protein; p less than 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 less than 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 less than 0.05), whereas changes in V1 receptor levels were not associated with changes in maximum inositol phosphate levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Trinder
D
D
University of Melbourne, Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.
Phillips
P A
PA
Risvanis
J
J
Stephenson
J M
JM
Johnston
C I
CI
D000262:Adenylyl Cyclases / Q000096:biosynthesis; D000818:Animals; D001127:Arginine Vasopressin; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone / Q000494:pharmacology*; D004195:Disease Models, Animal; D006973:Hypertension / Q000209:etiology*; D007295:Inositol Phosphates / Q000096:biosynthesis; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000502:physiology*; D015290:Second Messenger Systems; D012965:Sodium Chloride / Q000494:pharmacology*
D007295:Inositol Phosphates; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D000262:Adenylyl Cyclases