Diminazene aceturate-induced relaxation in isolated rat thoracic aorta: Contribution of cannabinoid and vanilloid...

The renin-angiotensin system (RAS) is a key regulator of cardiovascular homeostasis, and its alternative ACE2/Ang (1-7) axis exerts vasodilatory, anti-inflammatory, and antifibrotic effects. Functional crosstalk between the RAS and the endocannabinoid system (ECS) has been suggested. In this study, we investigated the relaxant effects of diminazene aceturate (DIZE), an experimental ACE2 activator, in endothelium-denuded rat thoracic aorta and evaluated the contribution of the ECS, TRPV1 receptors, along with tissue ACE2 and Ang (1-7) levels. Thoracic aortic rings isolated from 30 male Wistar albino rats were mechanically denuded of endothelium and mounted in organ baths under standard conditions. Following phenylephrine-induced precontraction, cumulative concentrations of DIZE were applied in the absence or presence of the CB1 receptor antagonist AM251, the CB2 receptor antagonist AM630, the TRPV1 antagonist capsazepine, the FAAH inhibitor URB597, or anandamide. The effects of DIZE on electrical field stimulation (EFS)-induced neurogenic relaxation responses were examined. ACE2 and Ang-(1-7) levels in thoracic aortic tissue were measured by ELISA. DIZE produced marked concentration-dependent relaxation in endothelium-denuded aortic rings. This effect was not significantly altered by CB1, CB2, or TRPV1 receptor antagonism, whereas anandamide and URB597 enhanced DIZE-induced relaxation. DIZE also augmented EFS-induced neurogenic relaxation, an effect reversed by AM630, while anandamide and URB597 suppressed the DIZE response. Although DIZE did not significantly change tissue ACE2 or Ang-(1-7) levels, the findings indicate an interaction with the ECS at multiple levels. These results suggest that DIZE may represent a promising therapeutic candidate in cardiovascular conditions associated with endothelial dysfunction.