title: Effects of angiotensin (1-7) upon right ventricular function in experimental rat pulmonary embolism.
abstract: Right ventricular (RV) dysfunction contributes to poor clinical prognosis after pulmonary embolism (PE). The present studies evaluate the effects of angiotensin (1-7) (ANG (1-7)) upon RV function during experimental PE in rats. Circulating ANG II increased 8-fold 6 hr after PE (47±13 PE vs. 6±3 pg/mL, control, p<0.05). ACE2 protein was uniformly localized in the RV myocardium of control rats, but showed a patchy distribution with some cells devoid of stain after 6 or 18 hr of PE. RV function decreased 18 hr after PE compared with control treated animals (19±4 vs. 41±1 mmHg, respectively, p<0.05; 669±98 vs. 1354±77 mmHg/sec, respectively, p<0.05), while left ventricular function (LV) was not significantly changed. Animals treated with ANG (1-7) during PE showed improved RV +dP/dt and peak systolic pressure development to values not significantly different from control animals. Protection of RV function by ANG (1-7) was associated with improved arterial blood sO2, base excess and pH. Supplemental delivery of ANG (1-7) reduced the development of RV dysfunction, suggesting a novel approach to protecting RV function in the setting of acute experimental PE.
authors.affiliation: Department of Emergency Medicine, Carolinas Medical Center, Charlotte, NC 28232-2861, USA. jwatts@carolinas.org
authors.forename: J A
authors.initials: JA
authors.lastname: Watts
authors.forename: M A
authors.initials: MA
authors.lastname: Gellar
authors.forename: L
authors.initials: L
authors.lastname: Stuart
authors.forename: M
authors.initials: M
authors.lastname: Obraztsova
authors.forename: M R
authors.initials: MR
authors.lastname: Marchick
authors.forename: J A
authors.initials: JA
authors.lastname: Kline
mesh_terms: D000803:Angiotensin I / Q000378:metabolism / Q000494:pharmacology*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism / Q000494:pharmacology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011655:Pulmonary Embolism / Q000150:complications* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018497:Ventricular Dysfunction, Right / Q000209:etiology / Q000378:metabolism; D016278:Ventricular Function, Right / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D010446:Peptide Fragments; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)