Cardiac AT(2)R expression is upregulated in the normal process of aging. In this study we determined the contribution of AT(2)R to chronic
antihypertensive and remodelling effects of AT(1)R blockade in aged hypertensive rats. Adult (20 weeks) and senescent (20 months) spontaneously hypertensive rats (SHRs) were treated with either the AT(1)R antagonist,
candesartan cilexetil (2 mg/kg/day), the AT(2)R antagonist,
PD123319 (10 mg/kg/day), or a combination of the 2 compounds. Mean arterial pressure (MAP) and left ventricular volume were markedly decreased by
candesartan cilexetil, however, simultaneous treatment with
PD123319 had no additional effect on either parameter. Perivascular
fibrosis was significantly reduced by
candesartan cilexetil in aged animals only, and this effect was reversed by concomitant
PD123319 administration. Vascular
hypertrophy was reduced by
candesartan cilexetil, and these effects were reversed by simultaneous
PD123319. These results suggest that AT(2)R stimulation does not significantly influence the
antihypertensive effect of chronic AT(1)R blockade, but plays a role in the regulation of vascular structure. The severe degree of cardiac perivascular
fibrosis in senescent animals was regressed by AT(1)R blockade and this effect was reversed by simultaneous AT(2)R inhibition, demonstrating an antifibrotic role of AT(2)R stimulation in the aging hypertensive heart.