Diminazene Aceturate-Induced Relaxation in Isolated Rat Thoracic Aorta: Contribution of Cannabinoid and Vanilloid Signaling.

Okcay Y.; Rumanli Z.; Avci E.; Vural I. · European journal of pharmacology · 2026

**Background & Methods** This experimental pharmacology study investigated the vasodilatory mechanisms of diminazene aceturate (DIZE), an ACE2 activator, using isolated endothelium-denuded rat thoracic aortic rings from 30 male Wistar albino rats. Researchers evaluated DIZE-induced relaxation responses in the presence of selective antagonists targeting cannabinoid receptors (CB1, CB2), TRPV1 receptors, and the endocannabinoid system (ECS), while measuring tissue ACE2 and angiotensin (1-7) levels via ELISA. **Key Findings** • DIZE produced marked concentration-dependent relaxation in endothelium-denuded aortic rings; this effect was not significantly altered by CB1, CB2, or TRPV1 receptor antagonism alone, suggesting these pathways are not primary mediators of the direct relaxant effect. • Anandamide (an endogenous cannabinoid) and URB597 (a FAAH inhibitor that increases endocannabinoid levels) enhanced DIZE-induced relaxation, indicating functional crosstalk between the ACE2/angiotensin (1-7) axis and the ECS at multiple regulatory levels. • DIZE augmented electrical field stimulation (EFS)-induced neurogenic relaxation, with CB2 receptor antagonism (AM630) reversing this effect, while anandamide and URB597 suppressed the DIZE response in this context, suggesting complex interactions in neurovascular signaling. **Dosage & Administration** Not reported. The study utilized cumulative concentrations of DIZE applied to organ bath preparations without specification of absolute doses. **Safety & Adverse Effects** Not reported. This was an isolated tissue preparation study without in vivo safety data or adverse effect documentation. **Evidence Quality** This preclinical in vitro study has significant limitations regarding clinical translational value. The use of endothelium-denuded aortic rings eliminates the endothelial layer critical for in vivo vascular physiology, limiting physiological relevance. The study was conducted exclusively in rat tissue, and findings require validation in intact vascular preparations and animal models before human applicability can be assessed. The apparent negative findings with receptor antagonists contrasted against enhancement by ECS modulators suggests complex, incompletely characterized mechanisms. As a 2026 publication, methodology and peer review status require verification. Overall, this represents early-stage basic science evidence with low to moderate strength for informing clinical applications in cardiovascular disease.

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