Cyclic intermittent hypoxia enhances renal sympathetic response to ICV ET-1 in conscious rats.
To test the hypothesis that central changes in sympathoregulation might contribute to sympathoexcitation after cyclic intermittent hypoxia (CIH) we exposed male Sprague-Dawley rats to CIH or to room air sham (Sham) for 8h/d for 3 weeks. After completion of the exposure we assessed heart rate, mean arterial pressure and renal sympathetic nerve activity in conscious animals before and after intracerebroventricular (i.c.v.) administration of endothelin-1 (ET-1, 3 pmol). CIH-exposed animals had a significantly greater sympathetic response to ET-1 than did Sham-exposed animals (CIH 137.8+/-15.6% of baseline; Sham 112.2+/-10.0% of baseline; CIH vs. Sham, P=0.0373). This enhanced sympathetic response to i.c.v. ET-1 was associated with greater expression of endothelin receptor A (ETA) protein in the subfornical organs of CIH-exposed relative to Sham-exposed rats. We conclude that 3-week CIH exposure enhances central ET-1 receptor expression and the sympathetic response to i.c.v. ET-1 suggesting central endothelin may contribute to the sympathetic and hemodynamic response to cyclic intermittent hypoxia.
Pulmonary and Sleep Research Laboratory, Division of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Jianhua
J
Huang
Tian
T
Xie
Yuming
Y
Wu
Xianghong
X
Li
Sara
S
Lusina
En-Sheng
ES
Ji
Shuanglin
S
Xiang
Yuzhen
Y
Liu
Shiva
S
Gautam
J Woodrow
JW
Weiss
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003243:Consciousness; D019332:Endothelin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D007276:Injections, Intraventricular; D007668:Kidney / Q000294:innervation; D008297:Male; D010507:Periodicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000378:metabolism; D013356:Subfornical Organ / Q000187:drug effects / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D013997:Time Factors
D019332:Endothelin-1; D044022:Receptor, Endothelin A