Angiotensin II type 2 receptor stimulation with compound 21 improves neurological function after stroke in female rats: a pilot study.

Authors:
Wael Eldahshan
Wael Eldahshan
Charlie Norwood VA Medical Center and Center for Pharmacy and Experimental Therapeutics
Tauheed Ishrat
Tauheed Ishrat
Jamia Hamdard (Hamdard University)
India
Bindu Pillai
Bindu Pillai
University of Alberta
Mohammed A Sayed
Mohammed A Sayed
Misr University for Science and Technology
Egypt
Abdulrahman Alwhaibi
Abdulrahman Alwhaibi
Clinical and Experimental Therapeutics
Abdelrahman Y Fouda
Abdelrahman Y Fouda
University of Georgia
United States
Adviye Ergul
Adviye Ergul
Medical College of Georgia
United States
Susan C Fagan
Susan C Fagan
College of Pharmacy
United States

Am J Physiol Heart Circ Physiol 2019 May 1;316(5):H1192-H1201. Epub 2019 Mar 1.

Program in Clinical and Experimental Therapeutics, Charlie Norwood Veterans Affairs Medical Center and University of Georgia, College of Pharmacy , Augusta, Georgia.

The angiotensin II type 2 receptor (ATR) agonist, compound 21 (C21), has been shown to be neurovascularly protective after ischemic stroke in male rats. In the current study, we aim to study the impact of C21 treatment on female rats. Young female Wistar rats were subjected to different durations of middle cerebral artery occlusion (MCAO) (3 h, 2 h, and 1 h) using a silicone-coated monofilament, treated at reperfusion with 0.03 mg/kg ip of C21 and followed up for different times (1, 3, and 14 days) after stroke. Behavioral tests were performed (Bederson, paw grasp, beam walk, and rotarod), and animals were euthanized for infarct size analysis and Western blot analysis. In vitro, primary male and female brain microvascular endothelial cells (ECs) were grown in culture, and the expression of the ATR was compared between males and females. At 1 day, C21 treatment resulted in an improvement in Bederson scores. However, at 3 days and 14 days, the impact of C21 on stroke outcomes was less robust. In vitro, the expression of the ATR was significantly higher in female ECs compared with male ECs. In conclusion, C21 improves Bederson scores after stroke in female rats when administered early at reperfusion. The ability of C21 to exert its neuroprotective effects might be affected by fluctuating levels of female hormones. The present study shows the neuroprotective impact of C21 on ischemic stroke in female rats and how the protective effects of C21 can be influenced by the hormonal status of female rodents.

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http://dx.doi.org/10.1152/ajpheart.00446.2018DOI Listing
May 2019
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