Administration of angiotensin II in the paraventricular nucleus protects gastric mucosa from ischemia-reperfusion injury.
Our previous study demonstrated that electrical stimulation of the hypothalamic paraventricular nucleus (PVN) protects against gastric ischemia-reperfusion (GI-R) injury, but it is still unknown whether angiotensin II (Ang II) in the PVN plays a role in the development of GI-R. The purpose of this study was to investigate the effect of Ang II in the PVN on GI-R injury. GI-R injury was induced in rats by clamping the celiac artery for 30 min, and then reperfusing for 30 min, 1 h, 3 h, 6 h or 24 h, respectively. A cannula was inserted into the unilateral PVN for microinjection of Ang II. The extent of gastric mucosal damage was determined by gross and histological methods. We found that microinjection of pharmacological doses of Ang II (3, 30, and 300 ng) into the PVN dose-dependently inhibited GI-R injury, and that Ang II (30 ng) markedly attenuated GI-R injury at 1 h and 3 h after reperfusion. The effect of Ang II was prevented by pretreatment with the Ang II AT1 receptor antagonist losartan (5 microg) into the lateral cerebral ventricle. Furthermore, the protective effect of Ang II on GI-R injury was abolished by propranolol (1 mg/kg, i.v.) or disconnection of the nerves innervating the adrenal glands, was augmented by sympathectomy or phentolamine (1 mg/kg, i.v.), and was not affected by subdiaphragmatic vagotomy or atropine (1 mg/kg, i.v.). These results indicate that the PVN is a responsive site for central Ang II-induced protection against GI-R injury. The central effects of Ang II are mediated by AT1 receptors in the PVN, and the peripheral effects by a sympathetic-adrenal gland/beta-adrenoceptor pathway.
Zhang
Yong-Mei
YM
Department of Pharmacology, School of Medicine, Zhejiang University, 388, Yu Hang Tang Road, Hangzhou 310058, China.
Wei
Er-Qing
EQ
Hu
Xia
X
Xu
Ming
M
Shi
Yue
Y
Zhang
Jian-Fu
JF
D000804:Angiotensin II / Q000008:administration & dosage*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects*; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology* / Q000517:prevention & control; D013562:Sympathectomy / Q000379:methods; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D011433:Propranolol; D019808:Losartan; D010646:Phentolamine