Canrenoic Acid, a Mineralocorticoid Receptor Antagonist, Attenuates Resistance Artery Remodeling in Stroke‐Prone Spontaneous Hypertensive Rats

Abstract

Chronic hypertension causes structural changes in the resistance vasculature through the process of remodeling. Middle cerebral artery (MCA) remodeling increases the risk for ischemic stroke. We have previously shown that the mineralocorticoid receptor (MR) is involved in MCA remodeling. Therefore, we hypothesized that MR antagonism with canrenoic acid (CANR) would attenuate the process. Six‐week old male stroke‐prone spontaneously hypertensive rats (SHRSP) were treated with CANR (20mg/kg/day, n=7) in the drinking water for six weeks. Untreated SHRSP were used as controls (n=12). MCA and mesenteric resistant artery (MRA) passive structure was analyzed by pressure myography. Data are shown as mean ± SEM, CANR vs control respectively. In the MCA, at 80mmHg, CANR treatment increased lumen diameter (277±6 vs 240±5μm, p<0.05) and decreased wall thickness (17.1±1.1 vs 25.6±1.2μm, p<0.05) and wall‐to‐lumen ratio (0.06±0.01 vs 0.11±0.01, p<0.05), without changing vessel stiffness (β‐coefficient: 10.4±1.4 vs 8.16±1.6, p<0.05). In the MRA, at 90 mmHg, CANR treatment reduced wall thickness (17.0±0.7 vs 27±1.7μm, p<0.05) and wall‐to‐lumen ratio (0.16±0.01 vs 0.10±0.01, p<0.05), without changing lumen diameter (274±8 vs 265±9μm) or vessel stiffness (β‐coefficient: 5.5±0.7 vs 5.5±0.5). These data suggest that MR antagonism attenuates cerebral and peripheral remodeling by different mechanisms.