Effect of Chronic Intermittent Hypoxia on Angiotensin II Receptors in the Central Nervous System

Autor: Morgan Rothman, Ann Mitzey, John M. Dopp, Robert C. Speth, Barbara J. Morgan, Nicole Schrimpf, Mark S. Brownfield
Rok vydání: 2018
Předmět:
Zdroj: Clinical and Experimental Hypertension. 41:130-136
ISSN: 1525-6006
1064-1963
Popis: Chronic intermittent hypoxia (CIH) increases basal sympathetic nervous system activity, augments chemoreflex-induced sympathoexcitation, and raises blood pressure. All effects are attenuated by systemic or intracerebroventricular administration of angiotensin II type 1 receptor (AT1R) antagonists. This study aimed to quantify the effects of CIH on AT1R- and AT2R-like immunoreactivity in the rostroventrolateral medulla (RVLM) and paraventricular nucleus of the hypothalamus (PVN), central regions that are important components of the extended chemoreflex pathway. Eighteen Sprague-Dawley rats were exposed to intermittent hypoxia (FIO2 = 0.10, 1 min at 4-min intervals) for 10 hr/day for 1, 5, 10, or 21 days. After exposure, rats were deeply anesthetized and transcardially perfused with phosphate buffered saline (PBS) followed by 4% paraformaldehyde in PBS. Brains were removed and sectioned coronally into 50 µm slices. Immunohistochemistry was used to quantify AT1R and AT2R in the RVLM and the PVN. In the RVLM, CIH significantly increased the AT1R-like immunoreactivity, but did not alter AT2R immunoreactivity, thereby augmenting the AT1R:AT2R ratio in this nucleus. In the PVN, CIH had no effect on immunoreactivity of either receptor subtype. The current findings provide mechanistic insight into increased basal sympathetic outflow, enhanced chemoreflex sensitivity, and blood pressure elevation observed in rodents exposed to CIH.
Databáze: OpenAIRE