ANGIOTENSIN-CONVERTING ENZYME-INHIBITION IN THE PREVENTION AND TREATMENT OF CHRONIC RENAL DAMAGE IN THE HYPERTENSIVE FAWN-HOODED RAT

The spontaneously hypertensive fawn-hooded rat (FHH) develops accelera ted albuminuria and focal glomerular sclerosis (FGS), leading to ESRD and shortening of lifespan. The FHH is characterized by moderate syste mic hypertension, a relatively low afferent to efferent arteriolar res istance ratio, and glomerular hypertension. The FHH study presented he re was designed to examine the efficacy of early-onset, late-onset, or early-temporary angiotensin I-converting enzyme inhibition (ACE-i) in ameliorating long-term hypertension and FGS, and improving survival, as well as to relate its protective efficacy to preexistent FGS and to reduction of glomerular pressure (P-GC) Untreated rats developed hype rtension and high P-GC, and all (N = 22) except one died of ESRD withi n the 72-wk follow-up period. Early-onset (at 7 wk of age) ACE-i preve nted development of systemic and glomerular hypertension, and it large ly prevented proteinuria and FGS; all rats survived throughout the fol low-up period. Rats treated with late-onset (22 wk) ACE-i were hyperte nsive and proteinuric at the start of ACE-i, and they showed beginning FGS. ACE-i corrected the hypertension, albuminuria, and P-GC but coul d not fully prevent some hypertension, albuminuria, and FGS at the lat er stage. Early-temporary (7 to 22 wk) ACE-i adequately controlled blo od pressure and development of FGS during therapy, but after withdrawa l of ACE-i, systemic and glomerular hypertension developed as in untre ated animals. This regimen postponed but did not control FGS developme nt and early mortality. The results of this study indicate that: (1) e arly-onset ACE-i very effectively protects against development of rena l damage in the FHH; (2) this protection is associated with normalizat ion of the elevated glomerular capillary pressure; (3) ACE-i cannot co mpletely prevent further development of previously established FGS, de spite lowering glomerular capillary pressure; (4) early-temporary ACE- i has no long-term controlling effect on arterial and glomerular press ure, and it cannot control development of FGS.