Vasopressin response in collecting ducts of rats resistant to mineralocorticoid hypertension.
In previous studies we found that vasopressin stimulation of both cyclic AMP (cAMP) formation in cortical collecting tubules (CCT) and sodium reabsorption in isolated perfused kidneys was markedly exaggerated in rats with mineralocorticoid hypertension. In the present study, we tested the response (cAMP accumulation) of cortical and outer medullary collecting tubules (OMCT) to vasopressin in two rat models that are resistant to deoxycorticosterone acetate (DOCA)-induced hypertension, the Wistar-Furth strain and NaCl-deficient rats. The blood pressure of normal outbred Wistar rats rose to hypertensive levels (systolic pressure more than 165 mm Hg) during a 5-week treatment with DOCA (10 mg/week) and 1% saline to drink. Significant hypertrophy of the heart and kidneys was also observed. Vasopressin (10(-8) M)-induced cAMP formation was enhanced 3.4-fold in the CCT (OMCT unchanged) of hypertensive rats compared with normotensive controls. Significant hypertrophy (as indexed by tubule diameter) of the CCT but not the OMCT was also observed in DOCA-salt hypertensive rats. Restriction of dietary NaCl (0.13% in chow, tap water to drink) completely prevented DOCA-induced hypertension, organ and CCT hypertrophy, and enhancement of vasopressin-stimulated cAMP formation in the CCT. In Wistar-Furth rats, DOCA-salt treatment did not alter blood pressure or cause significant organ hypertrophy. However, DOCA-salt treatment enhanced vasopressin-stimulated cAMP formation by 4.1-fold in CCT of Wistar-Furth rats, with significant tubular hypertrophy in the CCT but not the OMCT. We conclude that DOCA-induced hypertension and changes in CCT function are dependent on excess dietary NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)
Jeffries
W B
WB
Department of Medicine, Creighton University School of Medicine, Omaha, Neb.
McArdle
S
S
Bockman
C
C
Abel
P W
PW
Pettinger
W A
WA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D000242:Cyclic AMP / Q000737:chemistry; D003900:Desoxycorticosterone / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D006984:Hypertrophy; D007685:Kidney Tubules, Collecting / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D051381:Rats; D011920:Rats, Inbred WF; D012982:Sodium, Dietary / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology*
D012982:Sodium, Dietary; D014667:Vasopressins; D003900:Desoxycorticosterone; D000242:Cyclic AMP