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Aldosterone Acutely Enhances Coronary Artery Contractile Responsiveness without Inducing Endothelial Dysfunction

Inappropriate activation of the renin‐angiotensin‐aldosterone system (RAAS) contributes to increased contractility of the vasculature in many disease states. Activation of vascular mineralocorticoid receptors (MR) has recently been implicated as an important regulator of vascular function. In vascular smooth muscle, genomic mechanisms of MR activation have been implicated in vascular contractility, however, little is known regarding non‐genomic MR signaling as a modulator of vascular contractility. Based on available evidence, we hypothesized that acute aldosterone incubation of murine coronary arteries ex vivo would enhance coronary contractility via non‐genomic MR activation in smooth muscle cells (SMC). Wire myography experiments were conducted on isolated coronary arteries from C57BL/6J mice. Contractile responses to KCl (10mM–45mM) were determined by repeated measures design before and following one hour aldosterone treatment (10nM or 100nM). KCl induced dose‐dependent coronary vasoconstriction that was enhanced by aldosterone incubation in a dose dependent fashion. Vasoconstriction to 20mM KCl was doubled following incubation with 10nM aldosterone and increased >3‐fold following incubation with 100nM aldosterone. Pretreatment with the selective MR antagonist eplerenone (10μM) did not significantly reduce enhanced KCl vasoconstriction in response to 100nM aldosterone. Furthermore, endothelium‐dependent coronary vasodilation to acetylcholine was unchanged following one hour aldosterone incubation regardless of dose. In conclusion, acute aldosterone incubation enhances coronary vasoconstrictor responses to KCl that, at least in response to high dose aldosterone (100nM), is not dependent on MR activation. Importantly, this effect appears to be smooth muscle‐specific and not secondary to aldosterone‐induced endothelial dysfunction as acute aldosterone incubation did not impair endothelium‐dependent coronary vasodilation. These results highlight important vascular cell‐specific effects of aldosterone that may underlie enhanced coronary contractility in disease states associated with inappropriate RAAS activation.