Besides the well-known renal effects of
aldosterone, the
hormone is now known to have direct vascular effects. Clinical observations underline substantial adverse effects of
aldosterone on cardiovascular function. The source of systemic circulating
aldosterone is the adrenal gland zona glomerulosa cells through stimulus-secretion coupling involving depolarization, opening of L- and
T-type calcium channels and
aldosterone synthase activation. Local formation and release in peripheral tissues such as perivascular fat is recognized. Where does
aldosterone affect the vasculature?
Mineralocorticoid receptors (MRs) are present in endothelial and vascular smooth muscle cells, and MR-independent pathways are also involved. The vascular effects of
aldosterone are complex, both concentration and temporal and spatial aspects are relevant. The acute response includes vasodilation through endothelial
nitric oxide formation and
vasoconstrictor effects through endothelial-contracting
cyclooxygenase-derived factors and a changed
calcium handling. The response to
aldosterone can change within the same blood vessels depending on the exposure time and status of the endothelium. Chronic responses involve changed levels of reactive
oxygen radicals, endothelial Na-influx and smooth muscle
calcium channel expression. Furthermore, perivascular cells for example mast cells have also been suggested to participate in the chronic response. Moreover, the vascular effect of
aldosterone depends on the status of the endothelium which is likely the cause of the very different responses to
aldosterone and MR treatment observed in human studies going from increased to decreased flow depending on whether the patient had prior
cardiovascular disease with endothelial dysfunction or not. A preponderance of constrictor versus dilator responses to
aldosterone could therefore be involved in the detrimental vascular actions of the
hormone in the setting of endothelial dysfunction and contribute to explain the beneficial action of MR blockers on blood pressure and target organ injury.