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

Authors

Barbara J Morgan, University of Wisconsin-Madison
Nicole Schrimpf, University of Wisconsin-Madison
Morgan Rothman, University of Wisconsin-Madison
Ann Mitzey, University of Wisconsin-Madison
Mark S Brownfield, University of Wisconsin-Madison
Robert Charles Speth, Nova Southeastern UniversityFollow
John M Dopp, University of Wisconsin-Madison

Publication Title

Clinical and Experimental Hypertension

Publisher

Taylor & Francis Group

ISSN

1064-1963

Publication Date

3-21-2018

Keywords

Immunohistochemistry, Rostroventrolateral medulla, Paraventricular nucleus of the hypothalamus, Chemoreflex, Sympathetic Nervous System, Blood Pressure, Rats

Abstract

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 (F_IO₂ = 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.

DOI

10.1080/10641963.2018.1451536

Volume

41

Issue

2

First Page

130

Last Page

136

Comments

This research was supported by a grant from the National Heart, Lung, and Blood Institute (UO-1 105365; J.M. Dopp, PI).

Disciplines

Medicine and Health Sciences | Pharmacy and Pharmaceutical Sciences

NSUWorks Citation

Morgan, Barbara J; Schrimpf, Nicole; Rothman, Morgan; Mitzey, Ann; Brownfield, Mark S; Speth, Robert Charles; and Dopp, John M, "Effect of Chronic Intermittent Hypoxia on Angiotensin II Receptors in the Central Nervous System." (2018). Faculty Articles. 112.
https://nsuworks.nova.edu/hpd_corx_facarticles/112