NAD(P)H oxidase in paraventricular nucleus contributes to the effect of angiotensin II on cardiac sympathetic afferent reflex.
We previously reported that reactive oxygen species (ROS) in paraventricular nucleus (PVN) modulated cardiac sympathetic afferent reflex (CSAR) and mediated the effect of angiotensin II (Ang II) in the PVN on the CSAR. In the present study, we investigated whether the NAD(P)H oxidase in the PVN was a key source of ROS which modulated the CSAR and contributed to the effect of Ang II on the CSAR. In anesthetized rats with sinoaortic denervation and vagotomy, renal sympathetic nerve activity (RSNA) and arterial pressure were recorded. The CSAR was evaluated by the RSNA response to epicardial application of bradykinin (BK). The NAD(P)H oxidase activity in the PVN was measured with lucigenin-enhanced chemiluminescent method. Microinjection of the NAD(P)H oxidase inhibitor, either apocynin (1.0 nmol) or phenylarsine oxide (PAO, 1.0 nmol), into the PVN significantly inhibited the CSAR. Microinjection of Ang II (0.3 nmol) into the PVN significantly augmented the CSAR. The effects of Ang II were not only abolished by pretreatment with either apocynin or PAO in the PVN but also partially inhibited by xanthine oxidase inhibitor allopurinol. Either epicardial application of BK or microinjection of Ang II into the PVN significantly increased NAD(P)H oxidase activity in the PVN. The effect of Ang II on NAD(P)H oxidase activity was abolished by pretreatment with AT(1) receptor antagonist losartan in the PVN. These findings suggested that NAD(P)H oxidase in the PVN was a major source of the ROS in modulating the CSAR, and the NAD(P)H oxidase contributes to the effect of Ang II on the CSAR.
Zhang
Ying
Y
Department of Physiology, Nanjing Medical University, Nanjing 210029, China.
Yu
Yang
Y
Zhang
Feng
F
Zhong
Ming-Kui
MK
Shi
Zhen
Z
Gao
Xing-Ya
XY
Wang
Wei
W
Zhu
Guo-Qing
GQ
D000344:Afferent Pathways / Q000187:drug effects; D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000294:innervation*; D008297:Male; D008845:Microinjections / Q000379:methods; D019255:NADPH Oxidases / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D019255:NADPH Oxidases; D001920:Bradykinin