Rapid increase in cardiac adrenomedullin gene expression caused by acute pressure overload: effect of the renin-angiotensin system on gene expression.

Abstract

To determine whether acute pressure overload (POL) can stimulate adrenomedullin (AM) production, the response of ventricular AM gene expression and plasma AM concentration to aortic banding was investigated in the rat. Furthermore, any link between AM expression and the renin-angiotensin system (RAS) enhanced by acute POL was examined using: a Ca channel blocker (manidipine), an angiotensin II type 1 receptor antagonist (candesartan), and an angiotensin-converting enzyme inhibitor (quinapril). Rats with acute POL produced by suprarenal aortic banding were studied 1, 5 and 14 days after surgery. Plasma AM concentrations in banded rats at day 1 increased 1.49-fold (p<0.01), then gradually declined to near the control level at day 14. Plasma AM concentrations correlated with plasma renin activity (PRA) (p<0.001). Adrenomedullin mRNA expression in the left ventricle (LV) increased 1.35-fold (p<0.05) at day 1. This increase was not significant at either 5 or 14 days after surgery. Adrenomedullin mRNA expression in the right ventricle on days 1 and 5 increased by 1.46-fold (p<0.05) and 1.52-fold (p<0.05), respectively. Candesartan, quinapril and manidipine reduced systolic blood pressure equally and activated PRA at day 1. However, augmented LV AM gene expression was suppressed completely by candesartan and quinapril, but remained unaffected by manidipine. In conclusion, POL induces a rapid increase in cardiac AM gene expression and in plasma AM concentrations. Cardiac AM transcription could therefore be partly regulated by RAS in suprarenal aortic banding rats.