Diastolic wall stress and ANG II in cardiac hypertrophy and gene expression induced by volume overload

We investigated the effects of diastolic wall stress (WS) and angiotensin I I (ANG II) on the left ventricular (LV) hypertrophy (LVH) induced by volume overload and on the gene expression of LV adrenomedullin (AM) and atrial n atriuretic peptide (ANP) in volume overload. Diastolic WS was pharmacologic ally manipulated with (candesartan) or without (calcium channel blocker man idipine) inhibition of ANG II type 1 receptors in aortocaval-shunted rats o ver 6 wk. Diastolic WS reached a plateau at 2 wk and subsequently declined regardless of further LVH. Although diastolic WS was decreased to a similar extent by both compounds, candesartan blunted LVH over 6 wk, whereas manid ipine blunted LVH at 2 wk but not after 4 wk. Levels of AM and ANP gene exp ression increased as LVH developed but were completely suppressed by candes artan over 6 wk. ANP expression level was also attenuated by manidipine ove r 6 wk, whereas AM expression level was suppressed at 2 wk but not after 4 wk by manidipine. We concluded that diastolic WS and ANG II might be potent stimuli for the LVH and LV AM and ANP gene expression in volume overload a nd that diastolic WS could be relatively involved in the early LVH and in t he gene expression of ANP rather than of AM.