Back to Search
Start Over
Macrophage depletion lowers blood pressure and restores sympathetic nerve α2-adrenergic receptor function in mesenteric arteries of DOCA-salt hypertensive rats
- Source :
- Thang, L V, Demel, S L, Crawford, R, Kaminski, N E, Swain, G M, van Rooijen, N & Galligan, J J 2015, ' Macrophage depletion lowers blood pressure and restores sympathetic nerve alpha(2)-adrenergic receptor function in mesenteric arteries of DOCA-salt hypertensive rats ', American Journal of Physiology. Heart and Circulatory Physiology, vol. 309, no. 7, pp. H1186-H1197 . https://doi.org/10.1152/ajpheart.00283.2015, American Journal of Physiology. Heart and Circulatory Physiology, 309(7), H1186-H1197. American Physiological Society
- Publication Year :
- 2015
-
Abstract
- We tested the hypothesis that vascular macrophage infiltration and O2− release impairs sympathetic nerve α2-adrenergic autoreceptor (α2AR) 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-α and p22 phox 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-α and p22 phox were localized near sympathetic nerves. Impaired α2AR 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 α2AR 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 α2AR function, causing enhanced NE release from sympathetic nerves.
- Subjects :
- Male
Sympathetic nervous system
medicine.medical_specialty
Sympathetic Nervous System
Cardiovascular Neurohormonal Regulation
Physiology
Blood Pressure
Nephrectomy
Norepinephrine (medication)
Rats, Sprague-Dawley
chemistry.chemical_compound
Desoxycorticosterone Acetate
Norepinephrine
Receptors, Adrenergic, alpha-2
Superoxides
Physiology (medical)
Adventitia
Internal medicine
Mineralocorticoids
medicine
Animals
Sodium Chloride, Dietary
Mesenteric arteries
Chemistry
Tumor Necrosis Factor-alpha
Peritoneal fluid
Macrophages
NADPH Oxidases
Mesenteric Arteries
Rats
medicine.anatomical_structure
Endocrinology
Blood pressure
Apocynin
Hypertension
Autoreceptor
Macrophages, Peritoneal
Clodronic Acid
Cardiology and Cardiovascular Medicine
medicine.drug
Subjects
Details
- ISSN :
- 15221539 and 03636135
- Volume :
- 309
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Accession number :
- edsair.doi.dedup.....e80d79857966299a5f36bd8d7fc8d962