Enhanced vasopressin (V2-receptor)-induced sodium retention in mineralocorticoid hypertension.
The deoxycorticosterone acetate (DOCA)-Na model of hypertension requires the presence of vasopressin for expression of high blood pressure. In the present study, the effects of vasopressin V2-receptor stimulation were examined in kidneys from rats receiving 1 wk of DOCA-Na or control (olive oil-tap water) treatment. The dose response to vasopressin (10(-10) to 10(-6) M) was tested in microdissected cortical collecting tubule (CCT) segments and adenosine 3',5'-cyclic monophosphate (cAMP) accumulation was significantly increased in segments from DOCA-Na rats vs. controls, confirming our previous study. In other experiments, kidneys from DOCA-Na and control rats were perfused with a modified Krebs-Henseleit buffer (37 degrees C, pH 7.4) and treated with either vehicle or 0.21-2.1 pM 1-desamino-8-D-arginine vasopressin (DDAVP). DDAVP caused significant (P less than 0.05) dose-related reductions in urine excretion (UV) and urinary sodium excretion (UNaV) in both DOCA-Na and control kidneys in the absence of changes in renal hemodynamics. However, DDAVP produced earlier and significantly greater reductions in UV and UNaV in kidneys from DOCA-Na vs. control rats. Percent fractional excretion of sodium was reduced significantly only in the DOCA-Na group (2.1 pM DDAVP). A small degree of antikaluresis was seen with DDAVP in both groups. Thus, DOCA-Na treatment augmented cAMP accumulation in the CCT, accompanied by a significant enhancement of DDAVP-stimulated urinary sodium and water reabsorption at the level of the intact kidney.(ABSTRACT TRUNCATED AT 250 WORDS)
Jeffries
W B
WB
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235.
Wang
Y
Y
Pettinger
W A
WA
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D003900:Desoxycorticosterone; D004573:Electrolytes / Q000652:urine; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000378:metabolism*; D017483:Receptors, Vasopressin; D012964:Sodium / Q000378:metabolism*
D004573:Electrolytes; D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D003900:Desoxycorticosterone; D012964:Sodium; D000242:Cyclic AMP; D003894:Deamino Arginine Vasopressin