Cyclic angiotensin-(1-7) contributes to rehabilitation of animal performance in a rat model of cerebral stroke

• Published in: Peptides (New York, N.Y. : 1980) Vol. 123; p. 170193
• Main Authors: Kuipers, Anneke, Moll, Gert N., Levy, Aharon, Krakovsky, Michael, Franklin, Rick
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2020
• Subjects: Angiotensin I - pharmacology; Angiotensin-(1-7); Animals; Arteries; Brain; Disease Models, Animal; Endothelium; Lanthionine; Lanthipeptide; Male; Peptide Fragments - pharmacology; Peptides, Cyclic - pharmacology; Rats; Rats, Sprague-Dawley; Recovery of Function - drug effects; Stroke - drug therapy; Stroke - physiopathology; Stroke Rehabilitation; Lanthionine; Brain; Lanthipeptide; Angiotensin-(1-7); Arteries; Endothelium
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2019.170193

•cAng-(1-7) induces an increase in cerebral capillary density.•cAng-(1-7) improves neurological severity score.•cAng-(1-7) improves performance in the stepping and forelimb placement tests.•cAng-(1-7) improves performance in the body swing test.•cAng-(1-7) is equally effective as bolus and via alzet pump.
Peptidase-resistant, lanthionine-stabilized angiotensin-(1-7), termed cAng-(1-7), has shown therapeutic efficacy in animal models of cardiovascular, metabolic, kidney and pulmonary disease. Goal of the present study was testing the capacity of subcutaneously administered cAng-(1-7) to induce rehabilitation of animal performance in the transient middle cerebral artery occlusion rat model of cerebral stroke. 24 h after ischemic stroke induction, cAng-(1-7) was administered for 28 days at a dose of 500 μg/kg/day, either daily via subcutaneous injection or continuously via an alzet pump. Both ways of administration of cAng-(1-7) were equally effective. Measurements were continued until day 50. Compared to vehicle, cAng-(1-7) clearly demonstrated significantly increased capillary density (p < 0.01) in the affected hemisphere and improved motor and somatosensory functioning. The modified neurological severity score (p < 0.001 at days 15 and 50), stepping test (p < 0.001 at days 36–50), forelimb placement test (p < 0.001 at day 50), body swing test (p < 0.001 at days 43 and 50) all demonstrated that cAng-(1-7) caused significantly improved animal performance. Taken together the data convincingly indicate rehabilitating capacity of subcutaneously injected cAng-(1-7) in cerebral ischemic stroke.