Steroidogenic acute regulatory protein/aldosterone synthase participates in signaling of angiotensin II/aldosterone-induced aortic remodeling and hypertension

It has traditionally been viewed that hypertension occurs as a consequence of sodium/volume retention via aldosterone produced in the adrenals by angiotensin II (AngII). This study tested the hypothesis that Ang II/aldosterone causes vascular morphological change and hypertension through the signaling of steroidogenic acute regulatory protein (StAR)/aldosterone synthase (AS) primarily initiated in the vessels. SD rats were selected for a 4-weeks period of observation after subcutaneous implantation of osmotic minipumps, and randomized to the following groups: AngII infusion (500 ng/kg/min); AngII plus AngII AT1 receptor blocker, telmisartan (10 mg/kg/day); AngII plus aldosterone receptor antagonist, spironolactone (100 mg/kg/day); Adrenalectomy before AngII infusion; Sham control received saline infusion. Adrenals and aorta from all groups were dissected for immunohistochemical analysis, and blood pressure was measured non-invasively. Relative to Sham control, AngII infusion enhanced protein levels of the AT1 receptor, StAR, AS, and their tissue expression in the adrenals and aorta, as identified by immunohistochemical staining. Treatment with telmisartan inhibited these alterations, but dietary spironolactone did not show any effects, suggesting that the StAR/AS signaling is associated with the AT1 receptor. In coincidence with development of aortic hypertrophy, collagen deposition and elevated blood pressure by AngII, morphological examination revealed that macrophage infiltration, myofibroblast proliferation and collagen deposition are enhanced, which are significantly blocked by both telmisartan and spironolactone. Removing adrenal glands by adrenalectomy showed negative effects on StAR/AS expression in the aorta, and only partially blocked AngII-induced morphological changes. These findings suggest that in aorta, the activation of upstream AT1 receptor is involved in the aldosterone production via signaling of StAR/AS, and blockade of downstream aldosterone receptor is associated with an attenuation of vascular hypertrophy and hypertension, indicating that anti-aldosterone drug could be selected as add-on drug in treatment of hypertension.