INCREASED EXPRESSION OF GLOMERULAR AT(1) RECEPTORS IN RATS WITH MYOCARDIAL-INFARCTION

Rats with congestive heart failure demonstrate striking intrarenal vas oconstriction that contributes to reduced renal excretory function. We previously demonstrated that inhibition of angiotensin action reverse s intrarenal vasoconstriction in rats 4-6 wk after coronary artery lig ation. In the present study we tested the hypothesis that abnormalitie s in the expression and regulation of glomerular angiotensin receptors contribute to the intrarenal vasoconstriction. Because glomerular ang iotensin type 1 (AT(1)) receptors normally downregulate in response to high local ANG II concentrations, we anticipated that glomerular AT(1 )-receptor expression would be reduced in rats after myocardial infarc tion (MI). To our surprise, the density of glomerular AT1 receptors wa s nearly double (97% increase, P < 0.002) that of controls, indicating an acquired abnormality in angiotensin receptor regulation. This was specific for renal glomeruli, because the density of angiotensin recep tors on renal vasculature was decreased in rats after MI compared with normal controls. Glomerular AT1-receptor expression was downregulated by an acute pharmacological infusion of ANG II and upregulated by acu te angiotensin-converting enzyme inhibition to a similar extent in MI and control rats. Renal cortical mRNA expression showed an increase in the renin mRNA-to-actin ratio and angiotensinogen-to-actin ratio, ind icating stimulation of the intrarenal angiotensin system in rats after MI. The data indicate a specific dysregulation of AT(1) receptors in glomeruli but not blood vessels after MI.