AJP - Regulatory, Integrative and Comparative Physiology, Vol 256, Issue 2 523-R530, Copyright © 1989 by American Physiological Society
Chronic CEI alters effect of low Na+ diet in normal and coarcted pups. I. BP, renin, and GFR
S. P. Bagby and E. Fuchs
Department of Medicine, Portland Veterans Administration Medical Center, Oregon Health Sciences University 97207.
To assess the renin-angiotensin (RA) dependence of evolving neonatally
induced coarctation hypertension (NICH) in inbred pups, we randomized
sex-matched littermates to a high dose of converting-enzyme inhibitor
(CEI:MK-421) or placebo from the time of neonatal aortic banding (coarcted)
vs. no banding (control). In phase 1 studies, pups were examined serially
on normal diet (Bagby and Fuchs, Hypertension In press.): chronic CEI
lowered systolic blood pressure (BP) equally in coarcted and controls and
failed to prevent systolic BP excess in coarcted dogs. In phase 2 studies,
the same pups were exposed to a low sodium (LS) diet at 4 mo of age, a time
when the untreated NICH model exhibits increased forelimb systolic BP.
Measurements of systolic BP, RA components, renal function, and
extracellular volume (ECV) were made before and serially during 12 days on
the LS diet. Responses of coarcted and control pups to the LS diet were
similar, with or without CEI, providing no evidence for exaggerated
angiotensin II (ANG II) dependence in evolving NICH. Independently of
coarctation status, chronic CEI significantly modified RA and renal
functional responses to the LS diet: a greater renin rise but abnormal
renin substrate fall, thus no rise in ANG I or ANG I generation rate; a
greater rise in creatinine and a trend toward a greater fall in glomerular
filtration rate (GFR). Despite these findings compatible with sustained ANG
II deficit, chronic CEI unexpectedly failed to impair maintenance of
systolic BP during a superimposed LS diet.(ABSTRACT TRUNCATED AT 250 WORDS)
