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

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.