Protection of retinal vasculature by losartan against apoptosis and vasculopathy in rats with spontaneous hypertension

Abstract

Objectives: Retinal blood vessels may develop vasculopathy and apoptosis in response to hypertension. The present study was aimed at testing the role of losartan, a specific antagonist of angiotensin II receptor type 1 receptor in regulation of vascular apoptosis in retinal vasculature with hypertension.

Methods: Losartan potassium was administered to spontaneously hypertensive rats (SHR). Blood pressure was measured in SHR as well as normotensive Wistar-Kyoto rats (WKY). Eye fundus was examined in living animals and then tissue specimens were collected for histochemistry by hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling (TUNEL), immunohistochemistry and transmission electron microscopy.

Results: Losartan treatment for 4-8 weeks reduced blood pressure of SHR to the normal levels seen in WKY. The losartan-treated SHR showed marked improvement of retinal vascular morphology compared with untreated SHR. The retinal blood networks of the treated SHR developed lower degrees of vasculopathy and apoptosis. TUNEL and transmission electron microscopy also revealed that losartan exerted its protective effects not only on endothelial cells but on pericytes as well. The blood vessels of losartan-treated animals also showed decreased expression of bax with elevation of B-cell CLL/lymphoma 2.

Conclusion: Treatment with losartan, a medicine that lowers blood pressure by blocking angiotensin II receptor type 1 receptor, can protect the retinal vasculature against hypertensive vascular injury by inhibiting apoptosis of vascular cells and by preventing hypertensive retinopathy.