Inhibition of Renin-Angiotensin System from Conception to Young Mature Life Induces Salt-Sensitive Hypertension via Angiotensin II-Induced Sympathetic Overactivity in Adult Male Rats

Abstract

Previous studies indicate that perinatal compromise of taurine causes cardiovascular disorders in adults via the influence of taurine on renin-angiotensin system (RAS). This study tested whether perinatal inhibition of the RAS would itself alter the adult cardiovascular system in a similar way. Female Sprague-Dawley rats were fed normal rat chow and given water alone (Control) or water containing captopril (400 mg/l) from conception until weaning. Then, the male offspring drank water or water containing captopril until 5 weeks of age followed by normal rat chow and water alone until 7 weeks of age. Thereafter, they drank water alone (Control, Captopril) or 1% NaCl solution (Control+1%, Captopril+1%). At 9 weeks of age, all animals were implanted with femoral arterial and venous catheters. Forty-eight hours later, blood chemistry, glucose tolerance, and hemodynamic parameters were determined in freely moving conscious rats. Then, the same experiments were repeated 2 days after captopril treatment. Body weights, kidney and heart to body weight ratios, fasting and non-fasting blood sugar, glucose tolerance, and heart rates were not significantly different among groups. Further, plasma sodium, mean arterial pressure, and sympathetic activity significantly increased whereas baroreflex sensitivity decreased in Captopril+1% compared to other groups. These changes were normalized by acute captopril treatment and the arterial pressure differences also by acute ganglionic and central adrenergic blockade. The present study suggests that inhibition of the RAS in the early life induces RAS overactivity, leading to salt-sensitive hypertension via sympathetic nervous system overactivity and depressed baroreflex sensitivity in adult male rats.