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Macrophage (Mϕ) Depletion Reduced Vascular Oxidative Stress, Restored α2 Adrenergic Autoreceptor (α2AR) Function and Attenuated Blood Pressure Development in Deoxycorticosterone Acetate (DOCA)‐salt Hypertensive Rats
Author(s) -
Thang Loc Vinh,
Garver Hannah,
Galligan James J
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.654.20
Subject(s) - endocrinology , medicine , idazoxan , blood pressure , adventitia , chemistry , agonist , autoreceptor , oxidative stress , stimulation , antagonist , receptor , prazosin
There is an increase in pro‐inflammatory Mϕ in mesenteric artery (MA) adventitia, and the α 2 AR regulating norepinephrine (NE) release from perivascular sympathetic nerves is impaired in DOCA‐salt model. The cause of this impairment and the contribution of Mϕ to the pathophysiology of salt‐sensitive hypertension are unknown. We tested the hypothesis that Mϕ release O 2 − , which disrupts α 2 AR function causing increased NE release and further increases in blood pressure in DOCA‐salt rats. Liposomal clodronate encapsulate (LEC) was used to deplete adventitial Mϕ in rat MA, (# Mϕ/frame, DOCA PBS: DOCA LEC, 39.96: 4.16, p<0.05). Mϕ depletion reduced vascular O 2 − (measured using dihydroethidium) (Δ σ DOCA PBS‐DOCA LEC: 23.85, p<0.05). α 2 AR function was also restored in Mϕ depleted animals. To establish this we used focal nerve stimulation and amperometry with microelectrodes to measure NE oxidation currents at the adventitial surface of MA in the presence α 2 AR agonist, UK 14304, and antagonist, Idazoxan. (Normalized 1μM UK 14304 and Idazoxan NE current % control respectively, DOCA LEC: DOCA PBS, 0.326: 0.611, & 2.74: 2.18, P<0.05). Lastly, using radio telemetry, we found that Mϕ depletion attenuated DOCA‐salt blood pressure development. (MAP on day 25–28,DOCA LEC: DOCA PBS, 154.8mmHg: 197.4mmHg, p<0.05). These data support the hypothesis that Mϕ increased blood pressure in DOCA‐salt rats by releasing O 2 − , which disrupted α 2 AR function and enhanced sympathetic nerve activity.