Macrophage depletion lowers blood pressure and restores sympathetic nerve [alpha]^sub 2^-adrenergic receptor function in mesenteric arteries of DOCA-salt hypertensive rats

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 309; no. 7; p. H1186
• Main Authors: Thang, Loc V, Demel, Stacie L, Crawford, Robert, Kaminski, Norbert E, Swain, Greg M, Van Rooijen, Nico, Galligan, James J
• Format: Journal Article
• Language: English
• Published: Bethesda American Physiological Society 01.10.2015
• Subjects: Blood pressure; Immunohistochemistry; Rodents; Veins & arteries
• ISSN: 0363-6135; 1522-1539

We tested the hypothesis that vascular macrophage infiltration and O2- release impairs sympathetic nerve a2-adrenergic autoreceptor (a2AR) function in mesenteric arteries (MAs) of DOCA-salt hypertensive rats. Male rats were uninephrectomized or sham operated (sham). DOCA pellets were implanted subcutaneously in uninephrectomized rats who were provided high-salt drinking water or high-salt water with apocynin. Sham rats received tap water. Blood pressure was measured using radiotelemetry. Treatment of sham and DOCA-salt rats with liposome-encapsulated clodronate was used to deplete macrophages. After 3-5, 10-13, and 18-21 days of DOCA-salt treatment, MAs and peritoneal fluid were harvested from euthanized rats. Norepinephrine (NE) release from periarterial sympathetic nerves was measured in vitro using amperometry with microelectrodes. Macrophage infiltration into MAs as well as TNF-a and p22phox were measured using immunohistochemistry. Peritoneal macrophage activation was measured by flow cytometry. O2- was measured using dihydroethidium staining. Hypertension developed over 28 days, and apocynin reduced blood pressure on days 18-21. O2- and macrophage infiltration were greater in DOCA-salt MAs compared with sham MAs after day 10. Peritoneal macrophage activation occurred after day 10 in DOCA-salt rats. Macrophages expressing TNF-a and p22phox were localized near sympathetic nerves. Impaired a2AR function and increased NE release from sympathetic nerves occurred in MAs from DOCA-salt rats after day 18. Macrophage depletion reduced blood pressure and vascular O2- while restoring a2AR function in DOCA-salt rats. Macrophage infiltration into the vascular adventitia contributes to increased blood pressure in DOCA-salt rats by releasing O2-, which disrupts a2AR function, causing enhanced NE release from sympathetic nerves.