Vasorelaxant and Antihypertensive Effects of Salicylaldehyde: Involvement of Renin-Angiotensin System and Calcium/Potassium Channel Modulation

ETHNOPHARMACOLOGICAL RELEVANCE: Natural products are widely used in traditional medicine for managing cardiovascular disorders, including hypertension. Salicylaldehyde, a naturally occurring aromatic aldehyde found in plant-derived preparations, remains poorly characterized regarding its vascular effects. AIM OF THE STUDY: This study aimed to evaluate the vasorelaxant and antihypertensive properties of salicylaldehyde and to elucidate its underlying mechanisms of action. MATERIALS AND METHODS: Molecular docking was performed to assess interactions with key vascular targets. In vitro vasorelaxant activity was investigated using isolated rat thoracic aortic rings precontracted with epinephrine (EP, 10 μM) or potassium chloride (KCl, 80 mM). The involvement of endothelium-dependent and independent pathways was examined using pharmacological inhibitors and angiotensin II-induced contraction assays. In vivo effects were evaluated following oral administration of salicylaldehyde (20 and 40 mg/kg) in normotensive and N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Blood pressure was measured using a tail-cuff system during acute (6 h) and sub-chronic (7 days) treatments. RESULTS: Salicylaldehyde showed strong binding affinities toward angiotensin-converting enzyme (ACE) and angiotensin II Type 1 Receptor. It induced concentration-dependent vasorelaxation, significantly reduced after endothelial removal and under KCl-induced contraction. Its effects were attenuated by inhibitors of ACE, ACE2, ATP-sensitive K CONCLUSION: Salicylaldehyde exerts antihypertensive effects via multiple mechanisms and may contribute to the cardiovascular activity of plant-derived remedies.