Differences in Mortality Rate between Abrupt and Progressive Carotid Ligation in the Gerbil: Role of Endogenous Angiotensin II

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Abstract
Studies have shown that in comparison to rapid occlusion of a vessel, gradual occlusion produces less severe tissue ischemia due to a more effective development of collateral circulation. As other studies have shown that collateral circulation can be enhanced by stimulation of the endogenous renin–angiotensin II system, it was hypothesized that this system is involved in the mechanism of protection against ischemia that obtains during gradual vascular occlusion. To test this hypothesis, mortality rates were evaluated in gerbils subjected to gradual vascular occlusion by means of progressive carotid ligation while simultaneously infused with inhibitors of the renin–angiotensin II cascade—enalaprilat or saralasin. Groups of animals with either abrupt or progressive carotid ligation infused with saline served as controls. Results showed that (1) in saline-infused animals, there was a significant decrease in the mortality rate of progressive-ligated animals when compared to abrupt-ligated animals, and (2) administration of either enalaprilat or saralasin to progressive-ligated animals resulted in mortality rates that were indistinguishable from those of saline-infused abrupt-ligated animals. These results suggest that the endogenous renin-angiotensin system is indeed involved in an adaptive mechanism that occurs during progressive ligation of the carotid artery, and more specifically, that the relatively benign effect of progressive carotid ligation may be due to the action of angiotensin II to stimulate the development of collateral circulation and reduce the severity of focal brain ischemia.