Angiotensin AT1 receptor blockers suppress ischemia/reperfusion-induced gastric injury in rats.
Ischemia/reperfusion (I/R) damages gastric mucosa via reactive oxygen species (ROS) activity. ROS was reportedly produced through angiotensin II stimulation in tissues such as kidney, heart and brain. To determine whether AT1 receptor plays a role in gastric mucosal damage, we examined the effect of AT1 receptor blocker (ARB; losartan, candesartan, valsartan) on I/R-induced gastric injury in rats. I/R produced microscopic gastric hemorrhagic injury, and increased gastric microvascular permeability and H(2)O(2) production in rats. The mucosal lesions induced by I/R were attenuated by pretreatment of each ARB. The increase in microvascular permeability was suppressed by losartan pretreatment. Additionally, I/R-caused H(2)O(2) activation was not observed by pretreatment of losartan, candesartan and valsartan. These results suggest that angiotensin II stimulation via AT1 receptor and following ROS production in the stomach contribute to the pathogenesis of the gastric I/R injury.
Nakagiri
A
A
Department of Pharmacotherapeutics, Doshisha Women's College of Liberal Arts, Kodo, Kyotanabe, Kyoto 610-0395, Japan. anakagir@dwc.doshisha.ac.jp
Sunamoto
M
M
Murakami
M
M
D000804:Angiotensin II / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D002199:Capillary Permeability / Q000187:drug effects; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects* / Q000473:pathology; D006861:Hydrogen Peroxide / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000804:Angiotensin II; D000068756:Valsartan; D006861:Hydrogen Peroxide; D014633:Valine; D019808:Losartan; C081643:candesartan