Abstract
Background
The renin-angiotensin system (RAS) plays a crucial role in pathophysiology of congestive heart failure and ventricular remodeling after myocardial infarction (MI). There are two components, systemic and local, in RAS. There has not been a study to analyze differentially the sequential changes of systemic and local RAS after MI. The aim of this study was to analyze the sequential change of the expression of angiotensinogen mRNA, the first component of the renin-angiotensin system, in liver and non-infarcted myocardium in rats after myocardial infarction.
Method
Female Sprague-Dawley rats (body weight 200-250 g) were subjected either to left coronary artery occlusion or to sham operation. And the rats were sacrificed at 1, 4, 18, 24 hours, 3 days, 2, 3 weeks. Hemodynamic measurement was performed and RNA was extracted from various tissues including liver and ventricle for the analysis of the expression of the angiotensinogen mRNA by northern blot analysis or RT-PCR.
Results
Coronary artery ligation resulted in comparable infarct sizes among rats at 3 weeks after MI and was accompanied by significant increases of LVEDP (preMI 11±2 vs postMI 21±3 mmHg, n=4). Systolic arterial pressure was reduced in animals with infarction (preMI 130±15 vs postMI 90±10 mmHgn n=4). The liver angiotensinogen mRNA levels increased at 4, 18, 24 hours after myocardial infarction and decreased at 3rd day to control values (Angiotensinogen/GAPDH;preMI 1.35±0.20 vs postMI 5.97±0.25, max 4-fold, n=3). After sham operation, the liver angiotensinogen mRNA levels increased also at 4, 18, 24 hours, but in a less degree (Angiotensinogen/GAPDH;preop. 2.15±1.17 vs postop. 3.41±1.76, max 1.5-fold, n=3). In contrast to the liver, small amounts of angiotensinogen mRNA were detectable in normal left ventricle of rat with RT-PCR. The myocardial angiotensinogen mRNA levels decreased transiently in acute phase after MI, and recovered at 3-day after MI and increased further afterwards upto 3rd month after MI.