Abstract 021: Macrophage-dependent Impairment of the Alpha 2-adrenergic Receptor Occurs in DOCA-salt but Not Obesity-associated Hypertension

Abstract

Inflammation and increased sympathetic activity contribute to hypertension. Alpha 2-adrenergic receptor (α2AR) activation decreases norepinephrine (NE) release from sympathetic nerves by inhibiting Ca 2+ channels. We hypothesized that macrophage infiltration into mesenteric arteries (MA) impairs α2AR in salt-sensitive and obesity-associated hypertensive rats. Uniphrectomized Sprague Dawley (SD) rats were given water (SHAM) or 200mg/kg DOCA (pellet, sc) and water containing 1% NaCl, 0.2% KCl (DOCA) for 4 weeks. A high fat diet (HFD, 60% kcal from fat, 0.33% NaCl, 1% K + ) or normal fat diet (NFD, 10% kcal from fat, 0.24% NaCl, 0.36% K + ) was given to a second group of SD rats for 20 weeks and to Dahl salt-sensitive (SS) rats for 24-26 weeks after weaning (3 weeks). Immunohistochemistry for CD163 (macrophage marker) was used to count macrophages in MA. Whole-cell patch clamp was used on dissociated celiac ganglion neurons to evaluate α2AR-mediated Ca 2+ current inhibition with NE (1 μM). Liposome-encapsulated clodronate (Clod) was used to deplete rats of macrophages. Plasma aldosterone levels were assessed by ELISA. Summary data is provided in Table 1. Systolic blood pressure was higher in DOCA vs SHAM and HFD vs NFD rats. Vascular macrophage number increased in DOCA vs SHAM but not in HFD vs NFD rats. NE inhibited Ca 2+ current to a greater degree in neurons of SHAM vs DOCA but not NFD vs HFD rats. Clodronate reduced vascular macrophages in all rats and preserved α2AR-mediated inhibition of Ca 2+ current in DOCA rats. HFD did not affect plasma aldosterone levels. Therefore, we conclude that macrophage-associated impairment of α2AR may only occur in states of mineralocorticoid and salt excess.