Effect Of Perinatal Captopril Treatment On Renal Function Of Young Adult, Conscious Rats: Exacerbation Due To Discontinuation Of Treatment

Abstract

Perinatal, systemic inhibition of the renin-angiotensin system appears to improve renal function and decrease hypertension in the adult spontaneously hypertensive rats, but some studies indicate that this early treatment can damage the kidney. Further, in normotensive, salt-resistant rats perinatal
inhibition of the renin-angiotensin system increases the hypertensive response of these animals to a high NaCl diet. This study tests the hypothesis that perinatal inhibition of angiotensin converting enzyme (i.e., from conception onward) decreases renal function in young adult normotensive rats, especially in rats in which the treatment is discontinued. Male Sprague-Dawley rats were treated from conception onward with oral captopril (lifetime), or treated with captopril from conception to 5 weeks of age (acute). A third group was untreated (control; n = 9/group). At 7 weeks of age, all rats were implanted with arterial, venous, and bladder catheters, and 48 hours later, arterial pressure was measured continuously in restrained, awake rats before, during, and after an intravenous
infusion of isotonic saline (5% of body weight, 0.5 ml/min). Urine and blood samples were collected before and up to 90 minutes after saline infusion. The lifetime (but not the acute) captopril treatment significantly blunted body weight gain (142.4 ± 3.4 g (lifetime), 207.0 ± 5.0 g (acute), and 221.2 ± 4.0 g (control)), heart weight (0.53 ± 0.02 g (lifetime), 0.83 ± 0.02 g (acute), and 0.85 ± 0.02 g (control)), and kidney weight (1.45 0 ± 02 g (lifetime), 2.20 ± 0.15 g (acute), and 1.86 ± 0.04 g (control)). The treatment reduced mean arterial pressure in the lifetime group but not in the acute group (86.8 ± 2.4 mm Hg (lifetime), 112.6 ± 2.7 mm Hg (acute), and 114.6 ± 1.4 mm Hg (control)). Although the acute captopril treatment did not alter mean arterial pressure, it lowered basal urine flow rate, sodium excretion, and fractional water excretion. Following saline infusion, water excretion, sodium excretion, and glomerular filtration rate were similar between the lifetime and the acute captopril-treated rats, but compared to controls all three functions were impaired in the treated groups. Fractional sodium excretion was not significantly different among the three groups throughout the study. Compared to the control, only the acute perinatal captopriltreated rats displayed lower percent water and sodium excretion per gram of kidney weight. These data suggest that perinatal angiotensin converting enzyme inhibition blunts renal function in young adult rats.