Evolutional Change of Vasoactive Substances in Rat Model of Chronic Heart Failure

Kim, Cheol Ho; Zo, Joo Hee; Seo, Jung Don; Lee, Young Woo; Edwards, Brooks

Abstract

BACKGROUND
Myocardial infarction(MI) in the rat is a model of ventricular dysfunction which is associated with activation of compensatory neurohumoral systems. This stydy was designed to determine the temporal evolution of the regulatory factors-atrial natriuretic peptide(ANP), endothelin(ET), plasma renin activity(PRA) in rats with more than moderate sized MI at 1,4,8 weeks in comparison to normal rats.
METHODS AND RESULTS
MI was created in female Sprague Dawley rats weighing 250gms to 300gms by ligating the anterior descending artery. Before sacrifice, hemodynamics were measured and blood was drawn in control rats(n=8) and rats with MI(n=7), 4(n=10), and 8 weeks(n=9) after surgery. Heart weight index increased from 329.0+/-7.3mg/gm at baseline to 380.6+/-18.4mg/gm, 441.1+/-23.2mg/gm at the 1st, 4th, and 8th weeks after MI. Plasma ANP increased in the 1st weeks and remained elevated(16+/-7, 259+/-65, 404+/-72, 494+/-73pg/ml at baseline, 1st, 4th, 8th weeks after MI respectively). Plasma endothelin was suppressed at 4th weeks but elevated at 8th week(7.8+/-0.2, 5.3+/-0.3, 11.9+/-1.3pg/ml at baseline, 4th, 8th weeks respectively). PRA, indirect index of plasma angiotensin also decreased at 4th week but elevated at 8th week(14.9+/-0.3, 9.8+/-1.0, 20.3+/-1.8ng/ml/hr at baseline, 4th, 8th weeks resepctively).
CONCLUSION
These results demonstrate a biphasic response of endothelin and PRA after MI despite the inhibitory effects of ANP. These data support the important differential regulation of humoral factors in the evolution of acute MI.