Aldosterone induces arterial stiffness in absence of oxidative stress and endothelial dysfunction

Abstract

Monocyte/macrophages participate in inflammatory responses that may play an important role in mineralocorticoid-induced vascular damage. We hypothesized that monocyte/macrophages modulate aldosterone effects on oxidative stress, endothelial function, and ultimately vascular stiffness. Adult heterozygous osteopetrotic (Op/+) and wild-type mice were infused with aldosterone (600 microg/kg per day s.c. with Alzet osmotic minipumps) and received 1% NaCl in drinking water or were infused with vehicle for 14 days. Blood pressure was measured by the tail-cuff method. Endothelial function was determined in mesenteric arteries on a pressurized myograph by the response to acetylcholine following norepinephrine preconstriction. Extracellular matrix was quantified by immunohistochemistry, reactive oxygen species by image analysis of dihydroethidium staining, and reduced nicotinamide adenine dinucleotide phosphate oxidase activity by chemiluminescence. Body weight and blood pressure did not change following aldosterone treatment. Aldosterone induced stiffening of resistance arteries among all treated animals, as reflected by decreased sum of squares of strain from 2.07 +/- 0.15 to 1.54 +/- 0.29 in wild type, and from 2.68 +/- 0.28 to 2.04 +/- 0.15 in Op/+, and increased fibronectin-to-elastin ratio from 1.12 +/- 0.40 to 4.52 +/- 0.47 and 0.92 +/- 0.47 to 5.26 +/- 0.88, respectively. Endothelial function was impaired and reactive oxygen species increased only in aldosterone-treated wild-type mice. Reduced nicotinamide adenine dinucleotide phosphate oxidase activity was unaffected. Monocyte/macrophage deficiency in Op/+ mice results in absence of aldosterone-induced oxidative stress and endothelial dysfunction, but does not play a role in aldosterone-induced arterial stiffness. Thus, although monocyte/macrophage-mediated inflammatory responses play a role in oxidative stress and endothelial dysfunction, vascular stiffening in response to aldosterone may be independent of inflammation.