Abstract TP100: Angiotensin Type 2 Receptor Stimulation With Compound 21 Improves Stroke Outcome in Female Rats: Possible Role for Peroxisome Proliferator-activated Receptor Gamma

Stroke ◽  
2018 ◽  
Vol 49 (Suppl_1) ◽  
Author(s):  
Wael Eldahshan ◽  
Bindu Pillai ◽  
Mohammed Sayed ◽  
Tauheed Ishrat ◽  
Adviye Ergul ◽  
...  
Keyword(s):  
Female Rats ◽  
Peroxisome Proliferator ◽  
Stroke Outcome ◽  
Receptor Stimulation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Angiotensin Type 2 Receptor ◽  
Compound 21 ◽  
Angiotensin Type

Abstract WP101: Involvement of the Contralesional Angiotensin Type 2 Receptor in Compound 21 Mediated Functional Recovery After Stroke

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Abdelrahman Y Fouda ◽  
Tauheed Ishrat ◽  
Heba Ahmed ◽  
Bindu Pillai ◽  
Sandeep Artham ◽  
...  
Keyword(s):  
Western Blotting ◽  
Functional Recovery ◽  
Artery Occlusion ◽  
Behavioral Outcome ◽  
Brain Hemisphere ◽  
Angiotensin Type 2 Receptor ◽  
Male Wistar Rats ◽  
Compound 21 ◽  
Angiotensin Type

Introduction: We have recently shown that the angiotensin type 2 receptor (AT2R) agonist, compound 21 (C21), provides sustained functional recovery after ischemic stroke. This was associated with upregulation of the AT2R and the neurotrophin, brain derived neurotrophic factor (BDNF), in the contralesional brain hemisphere. Here, we aimed to study the contribution of this hemisphere in C21 mediated functional recovery after stroke through localized knockdown of the AT2R. Methods: male wistar rats (34) received two intrastriatal injections of short hairpin RNA (shRNA) lentiviral particles against AT2R, or non-targeting control vector (NTC) into the left brain hemisphere to achieve localized AT2R knockdown. After 14 days, rats were subjected to 90 minutes right middle cerebral artery occlusion (MCAO) and received either C21 (0.03 mg/kg) or saline at reperfusion (IV) then daily (IP) for 7 days. Rats were blindly assessed for behavioral outcome up to 10 days as well as molecular analysis. Results (table): PCR and Western blotting confirmed successful knockdown of the AT2R in the left (contralesional) hemisphere by about 50%. All groups showed worsened outcome on days 1 to 3 then recovered on days 7 to 10. The C21/NTC group showed better behavioral outcome compared to other groups at days 7 and 10, while the saline/shRNA group was associated with the least recovery. Using Western blotting, C21/NTC group showed higher BDNF and lower proBDNF (pro-form) levels in the ischemic and contralesional hemispheres respectively. Expression of the pro-apoptotic P75NTR receptor of proBDNF was decreased with C21 treatment irrespective of AT2R knockdown. Conclusion: Contralesional AT2R could be involved in C21 mediated functional recovery after stroke.

scholarly journals Relaxin attenuates organ fibrosis via an angiotensin-type 2 receptor mechanism in aged hypertensive female rats

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0002722021
Author(s):  
Giannie Barsha ◽  
Sarah L Walton ◽  
Edmund Kwok ◽  
Katrina M Mirabito Colafella ◽  
Anita P Pinar ◽  
...  
Keyword(s):  
Vascular Function ◽  
Cardiac Fibrosis ◽  
Female Rats ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Spontaneously Hypertensive ◽  
Angiotensin Type 2 Receptor ◽  
Models Of Disease ◽  
Angiotensin Type

Background: The anti-fibrotic effects of recombinant human relaxin (RLX) in the kidney are dependent on an interaction between its cognate receptor (RXFP1) and the angiotensin type 2 receptor (AT2R) in male models of disease. Whether RLX has therapeutic effects, which are also mediated via the AT2R, in hypertensive adult and aged/reproductively senescent females is unknown. Thus, we determined whether treatment with RLX provides cardiorenal protection, via an AT2R-dependent mechanism, in adult and aged female stroke prone-spontaneously hypertensive rats (SHRSP). Methods: In 6- (6MO) and 15-month-old (15MO; reproductively senescent) female SHRSP, systolic blood pressure (SBP), glomerular filtration rate (GFR) and proteinuria were measured before and after 4 weeks treatment with vehicle (Veh), RLX (0.5 mg/kg/day s.c.) or RLX+PD123319 (AT2R antagonist; 3 mg/kg/day s.c.). Aortic endothelium-dependent relaxation and fibrosis of the kidney, heart and aorta were assessed. Results: In 6MO SHRSP, RLX significantly enhanced GFR by ~25% (P=0.001) and reduced cardiac fibrosis (P=0.01) as compared to vehicle-treated counterparts. These effects were abolished or blunted by PD123319 co-administration. In 15MO females, RLX reduced interstitial renal (P=0.02) and aortic (P=0.003) fibrosis, and lowered SBP (13±3 mmHg; P=0.04) relative to controls. These effects were also blocked by PD123319 co-treatment (all p<0.05 versus RLX treatment alone). RLX also markedly improved vascular function by ~40% (P<0.0001) in 15MO SHRSP, but this was not modulated by PD123319 co-treatment. Conclusion: The anti-fibrotic and organ-protective effects of RLX, when administered to a severe model of hypertension, conferred cardiorenal protection in adult and reproductively senescent female rats, to a great extent via an AT2R-mediated mechanism.

Attenuation of stroke damage by angiotensin II type 2 receptor stimulation via peroxisome proliferator-activated receptor-gamma activation

2018 ◽  
Vol 41 (10) ◽  
pp. 839-848 ◽  
Author(s):  
Bao-Shuai Shan ◽  
Masaki Mogi ◽  
Jun Iwanami ◽  
Hui-Yu Bai ◽  
Harumi Kan-no ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Peroxisome Proliferator ◽  
Gamma Activation ◽  
Receptor Stimulation ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals The angiotensin type 2 receptor agonist Compound 21 elicits cerebroprotection in endothelin-1 induced ischemic stroke

2014 ◽  
Vol 81 ◽  
pp. 134-141 ◽  
Author(s):  
Jason P. Joseph ◽  
Adam P. Mecca ◽  
Robert W. Regenhardt ◽  
Douglas M. Bennion ◽  
Vermali Rodríguez ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Receptor Agonist ◽  
Endothelin 1 ◽  
Angiotensin Type 2 Receptor ◽  
Compound 21 ◽  
Angiotensin Type
Sign in / Sign up

Export Citation Format

Share Document