Exercise training prevents arterial baroreflex dysfunction in rats treated with central angiotensin II.
Angiotensin II (Ang II)-induced arterial baroreflex dysfunction is associated with superoxide generation in the brain. Exercise training (EX) improves baroreflex function and decreases oxidative stress in cardiovascular diseases linked to elevated central Ang II. The aim of this study was to determine whether previous EX prevents baroreflex impairment caused by central administration of exogenous Ang II via an Ang II-superoxide mechanism. Four groups of rats were used: non-EX artificial cerebrospinal fluid infused, non-EX Ang II infused, EX artificial cerebrospinal fluid infused, and EX Ang II infused. Rats were treadmill trained for 3 to 4 weeks and subjected to intracerebroventricular infusion of Ang II over the last 3 days of EX. Twenty-four hours after the end of EX, the arterial baroreflex was assessed in anesthetized rats. Compared with non-EX artificial cerebrospinal fluid-infused rats, Ang II significantly decreased baroreflex sensitivity (maximum gain: 3.0+/-0.2% of maximum per millimeter of mercury versus 1.6+/-0.1% of maximum per millimeter of mercury; P<0.01), which was abolished by acute intracerebroventricular infusion of the Ang II type 1 receptor antagonist losartan and the reduced nicotinamide-adenine dinucleotide phosphate oxidase inhibitor apocynin. EX prevented the decrease in baroreflex sensitivity and downregulated Ang II type 1 receptor and NADPH oxidase subunit protein expression in the paraventricular nucleus of Ang II-infused rats. Finally, EX decreased superoxide production in the paraventricular nucleus of Ang II-infused rats. These results indicate that EX improves arterial baroreflex function in conditions of high brain Ang II, which is mediated by the central Ang II type 1 receptor and associated with a reduction in central oxidative stress.
Pan
Yan-Xia
YX
Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198-5850, USA.
Gao
Lie
L
Wang
Wei-Zhong
WZ
Zheng
Hong
H
Liu
Dongmei
D
Patel
Kaushik P
KP
Zucker
Irving H
IH
Wang
Wei
W
D000804:Angiotensin II / Q000008:administration & dosage*; D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000517:prevention & control*; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D005080:Exercise Test; D008297:Male; D019255:NADPH Oxidases / Q000096:biosynthesis; D018384:Oxidative Stress / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis; D013481:Superoxides / Q000008:administration & dosage / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*
D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D013481:Superoxides; D000804:Angiotensin II; D019255:NADPH Oxidases