Abstract 1109: Aldosterone and Not Angiotensin II is an Early Inducer of the Expression of Renal Profibrotic Factors in Saline-Drinking Stroke-Prone Spontaneously Hypertensive Rats
Aldosterone induces renal injury independent of raising blood pressure suggesting a direct effect of aldosterone on tissue damage. Aldosterone can induce plasminogen activator inhibitor-1 in cardiovascular and renal tissues, which may be dependent on transforming growth factor-β1 (TGF-β1) activation. In the present study, we examined the effect of bilateral adrenalectomy (ADX) on the expression of PAI-1 and other factors related to fibrosis in kidneys of stroke- prone spontaneously hypertensive rats (SHRSP) and the ability of aldosterone or angiotensin II (Ang II) infusion to restore these levels. Saline-drinking male SHRSP underwent ADX (n=6), sham operation for adrenalectomy (SHAM, n=3), ADX + Angiotensin II (ADX+Ang II, 25 ng/min, subcutaneously, n=6) or ADX + aldosterone (ADX+ALDO, 40 μg/kg/day, subcutaneously, n=6). Two weeks later, circulating aldosterone levels were reduced to the limit of detection, renal PAI-1, TGF-β1 and osteopontin expression were decreased several fold and SMAD-7 (an inhibitory regulator of TGF-β1 action) expression was increased in ADX when compared with SHAM. Infusion of aldosterone into ADX SHRSP restored the renal expression of PAI-1, TGF-β1 and osteopontin mRNA and reduced that of SMAD-7. The ADX+Ang II SHRSP group, however, did not display increased PAI-1, TGF-β1, or OPN expression compared with ADX. These findings suggest that ALDO and Ang II have distinct roles in the renal injury in saline-drinking SHRSP model and would be consistent with the notion that the adverse renal effects of Ang II are in large part dependent on the participation of ALDO.