Renin-Angiotensin II Response to the Hemodynamic Pathology of Ovines With

We studied the response of the renin-angiotensin system (RAS) to a surgically created ventricular septal defect (VSD) in immature ovines and also the role of angiotensin n in the pathophysiology of VSD in the chronically instrumented ovine. Plasma renin activity (PRA) was increased from 2.39±1.1 to 3.78±1.4 ng/ml/hr (p<0.05, n=17) after VSD but not after sham procedure. The change in PRA was positively correlated with the amount of left-to-right shunt through the VSD (r=0.74, /?<0.05). Inhibition of angiotensin II effect with saralasin (10 pg/kg/ min) or angiotensin II production with captopril (2 mg/kg) lowered systemic resistance (RJ by 14 % and 34%, respectively (p<0.05), and raised pulmonary resistance (Rp) by 35 % and 77%, respectively (p<0.05). Thirty minutes following captopril, the ratio of pulmonary to systemic flow (Qp/QJ decreased from 3.31±0.18 to 2.15±0.18 (p<0.05) while total pulmonary flow fell from 7.15±0.38 to 5.92±0.34 l/min/M2 (p<0.05, n = l l). Systemic flow increased from 2.17±0.14 to 2.86±0.33 l/min/M2 (p<0.05) despite a reduction in left atrial pressure (17.3±1.0 vs. 13.0±1.7, p<0.01). Reinfusion of angiotensin II (0.02 /ig/kg/min) into the central aorta after captopril returned the hemodynamics to baseline including a rise in R, and fall in Rp. Exogenous angiotensin II alone (0.08 /ig/kg/min) or a threefold stimulation in PRA wit