The antiproteinuric action of enalapril in stroke-prone spontaneously hypertensive rats is unrelated to alterations in urinary prostaglandins.
We examined whether the renal protective effect of the angiotensin I converting enzyme inhibitor enalapril in stroke-prone spontaneously hypertensive rats (SHRSP) is dose-related and associated with alterations in the urinary excretion of prostaglandin (PG) E2 and 6-keto-PGF1 alpha, a stable breakdown product of prostacyclin. Enalapril maleate at 1.5, 5 and 15 mg/kg/day or vehicle was chronically administered to saline-drinking SHRSP (six per group) starting at 8.1 weeks of age. Vehicle-treated SHRSP developed severe hypertension, proteinuria and strokes (age at death, 14 +/- 1 weeks; mean +/- S.E.). Enalapril prolonged survival dose-dependently and reduced proteinuria; all SHRSP given 15 mg/kg/day lived beyond 23 weeks of age without evidence of stroke or proteinuria. There was no effect of enalapril at any dose on systolic arterial blood pressure in spite of variable levels of urinary protein excretion and onset of stroke in the different groups. Likewise, urinary 6-keto-PGF1 alpha and PGE2 excretion did not differ among the groups except for an increase in 6-keto-PGF1 alpha in the 15 mg/kg/day group at one week after initiation of enalapril therapy. These results are consistent with a dose-related renal protective action of enalapril in saline-drinking SHRSP that is not closely associated with sustained alterations in urinary excretion of renal vasodilatory PGs.
Stier
C T
CT
Department of Pharmacology, New York Medical College, Valhalla.
Mahboubi
K
K
DiPippo
V A
VA
Levine
S
S
Chander
P N
PN
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000517:prevention & control*; D004656:Enalapril / Q000494:pharmacology*; D006973:Hypertension / Q000150:complications*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D011453:Prostaglandins / Q000652:urine*; D011507:Proteinuria / Q000517:prevention & control*; D051381:Rats; D011918:Rats, Inbred SHR
D011453:Prostaglandins; D004656:Enalapril