Angiotensin II promoted axonal regeneration in the optic nerve of adult rats via the AT2 receptor, an effect abolished by an AT2 antagonist but not an AT1 antagonist.
Angiotensin II promotes axonal regeneration in the central nervous system of adult mammals specifically via the AT2 receptor, revealing a novel neurotrophic function of the renin-angiotensin system.
The renin-angiotensin system (RAS) has been traditionally linked to blood pressure and volume regulation mediated through the angiotensin II (ANG II) type 1 (AT1) receptor. Here we report that ANG II via its ANG II type 2 (AT2) receptor promotes the axonal elongation of postnatal rat retinal explants (postnatal day 11) and dorsal root ganglia neurons in vitro, and, moreover, axonal regeneration of retinal ganglion cells after optic nerve crush in vivo. In retinal explants, ANG II (10(-7)-10(-5) M) induced neurite elongation via its AT2 receptor, since the effects were mimicked by the AT2 receptor agonist CGP 42112 (10(-5) M) and were entirely abolished by costimulation with the AT2 receptor antagonist PD 123177 (10(-5) M), but not by the AT1 receptor antagonist losartan (10(-5) M). To investigate whether ANG II is able to promote axonal regeneration in vivo, we performed optic nerve crush experiments in the adult rats. After ANG II treatment (0.6 nmol), an increased number of growth-associated protein (GAP)-43-positive fibers was detected and the regenerating fibers regularly crossed the lesion site (1.6 mm). Cotreatment with the AT2 receptor antagonist PD 123177 (6 nmol), but not with the AT1 receptor antagonist losartan (6 nmol), completely abolished the ANG II-induced axonal regeneration, providing for the first time direct evidence for receptor-specific neurotrophic action of ANG II in the central nervous system of adult mammals and revealing a hitherto unknown function of the RAS.
Lucius et al. (Mon,) conducted a other in Optic nerve injury. Angiotensin II vs. AT2 receptor antagonist PD 123177 or AT1 receptor antagonist losartan was evaluated on Axonal elongation and regeneration (GAP-43-positive fibers). Angiotensin II promoted axonal regeneration in the optic nerve of adult rats via the AT2 receptor, an effect abolished by an AT2 antagonist but not an AT1 antagonist.