Aldosterone Decreases Nitric Oxide Mediated Dilatation through a Histamine H2 Dependent Mechanism in Intracerebral Arteries from Human and Mice

Abstract

Background Prolonged exposure to aldosterone has a contractile effect through inhibition of NO-mediated vasodilatation in mice mesenteric arteries. This effect involves histamine release from perivascular mast cells. Furthermore, high plasma aldosterone gives exacerbated outcome after stroke. It was hypothesized that aldosterone affects intracerebral vessels by histamine receptor H2 activation resulting in vasospasms. Method: Changes in luminal diameter were measured in perfused intracerebral arteries (size 25–45 μm) from humans with operable brain tumors and mice. Results: Secondary dilatation (recovery) in response to high K+ was observed in human (50.4 %) and mice intracerebral arteries (52.5 %). Pretreatment with aldosterone (10-9M, 60 min) significantly inhibited recovery in mice (12.3 %). The inhibition was fully reversible. Pretreatment with N(G)-nitro-L-arginine methyl ester (10-5M) significantly inhibited recovery in response to high K+ in mice (13.5 %). Similar tendencies were seen on human intracerebral arteries. The effect of aldosterone on recovery in mice arteries was inhibited by the histamine H2 receptor antagonist cimetidine (10-5M, 55.3 %). RT-PCR showed expression of the mineralocorticoid receptor in human cerebral cortex and human intracerebral arteries. Conclusion Aldosterone inhibits NO dependent dilatation in both human and mice intracerebral arteries. The inhibition is mediated through the histamine H2 receptor. This mechanism could potentially be involved in cerebral vasospasms occurring after stroke. Foundation: Danish Research Council and Danish Heart Foundation.