Inhibition of renin‐angiotensin system from conception to young mature life induces salt‐sensitive increased blood pressure via angiotensin II‐induced sympathetic overactivity in adult male rats

Perinatal blockade of renin‐angiotensin system (RAS) has a long‐term antihypertensive effect in spontaneously‐hypertensive rats, whereas this treatment induces salt‐sensitive hypertension in adult normotensive strained rats. This study tests the hypothesis that inhibition of the RAS from conception to young mature life induces salt‐sensitive increased blood pressure via angiotensin II‐induced sympathetic overactivity in adult male rats. Female Sprague‐Dawley rats were fed normal rat chow and given water alone (Control) or water containing captopril (an angiotensin‐converting enzyme inhibitor, 400 mg/l; Captopril) from conception until weaning. After weaning, the male offspring drank water or water containing captopril until 5 weeks of age followed by normal rat chow and water alone for all rats until 7 weeks of age. Thereafter, they were given 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 samples were collected to measure non‐fasting blood glucose, hematocrit, and plasma sodium and potassium concentrations. Then arterial pressure and heart rate were continuously recorded and baroreflex sensitivity was determined by phenylephrine and sodium nitroprusside in freely moving conscious rats. After an overnight fasting, glucose tolerance tests were performed. All animals were then fed with a normal rat chow and captopril in drinking water for 2 days and the same experiments were repeated. Body weights, kidney weights, kidney to body weight ratios, heart to body weight ratios, fasting and non‐fasting blood sugar, glucose tolerance, and heart rates were not significantly different among groups, while plasma potassium levels significantly decreased in Control+1% and Captopril compared to Control groups. Further, resting mean arterial pressure significantly increased in Captopril+1% compared to other groups (Control 103.1 ± 2.1 mm Hg, Control+1% 97.6 ± 2.2 mm Hg, Captopril 100.6 ± 1.5 mm Hg, Captopril+1% 110.7 ± 1.4 mm Hg; p < 0.05). The increased mean arterial pressure of the Captopril+1% group is consistent to its sympathetic overactivity (estimated by arterial pressure variability), hypernatremia (Control 123.2 ± 0.0 mEq/l, Control+1% 124.0 ± 0.4 mEq/l, Captopril 124.6 ± 0.4 mEq/l, Captopril+1% 132.0 ± 0.6 mEq/l; p < 0.05), and blunted baroreflex sensitivity, compared to the other three groups. These differences were improved, at least in part, by two‐day oral captopril treatment. In addition, the arterial pressure differences were eliminated by either acute ganglionic blockade (hexamethonium) or acute central sympathetic inhibition (clonidine). The present study suggests that inhibition of the RAS in the early life induces RAS overactivity to cause salt‐sensitive increased blood pressure via sympathetic nerve stimulation and depressed baroreflex sensitivity in adult male rats. Support or Funding Information This work was supported by Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .