title: Renin-angiotensin II response to the hemodynamic pathology of ovines with ventricular septal defect.
abstract: 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 II 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 less than 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, p less than 0.05). Inhibition of angiotensin II effect with saralasin (10 micrograms/kg/min) or angiotensin II production with captopril (2 mg/kg) lowered systemic resistance (Rs) by 14% and 34%, respectively (p less than 0.05), and raised pulmonary resistance (Rp) by 35% and 77%, respectively (p less than 0.05). Thirty minutes following captopril, the ratio of pulmonary to systemic flow (Qp/Qs) decreased from 3.31 +/- 0.18 to 2.15 +/- 0.18 (p less than 0.05) while total pulmonary flow fell from 7.15 +/- 0.38 to 5.92 +/- 0.34 l/min/M2 (p less than 0.05, n = 11). Systemic flow increased from 2.17 +/- 0.14 to 2.86 +/- 0.33 l/min/M2 (p less than 0.05) despite a reduction in left atrial pressure (17.3 +/- 1.0 vs. 13.0 +/- 1.7, p less than 0.01). Reinfusion of angiotensin II (0.02 micrograms/kg/min) into the central aorta after captopril returned the hemodynamics to baseline including a rise in Rs and fall in Rp. Exogenous angiotensin II alone (0.08 micrograms/kg/min) or a threefold stimulation in PRA with furosemide (2 mg/kg) caused little hemodynamic effect.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pediatrics, University of Utah College of Medicine, Salt Lake City.
authors.forename: M M
authors.initials: MM
authors.lastname: Boucek
authors.forename: R
authors.initials: R
authors.lastname: Chang
authors.forename: D P
authors.initials: DP
authors.lastname: Synhorst
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D004195:Disease Models, Animal; D005665:Furosemide / Q000494:pharmacology; D006345:Heart Septal Defects, Ventricular / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects; D012504:Saralasin / Q000494:pharmacology; D012756:Sheep; D012757:Sheep Diseases / Q000503:physiopathology*
chemical_list: D000804:Angiotensin II; D005665:Furosemide; D002216:Captopril; D012083:Renin; D012504:Saralasin