Antihypertensive Effects of Benzaldehyde in Rats: Involvement of Endothelium-Independent and Endothelium-Dependent Vasorelaxation via Prostacyclin (PGI2)/cAMP Pathway Activation and Calcium Channel Inhibition

Aims: Globally, cardiovascular disorders represent the foremost contributor to mortality, and elevated arterial pressure constitutes one of their principal risk determinants. Despite the availability of various treatments, optimal blood pressure control is rarely achieved. The present work was undertaken to assess the antihypertensive and vasorelaxant properties of benzaldehyde, a naturally occurring aromatic aldehyde whose role in the regulation of arterial pressure has, to our knowledge, not yet been documented. Materials and Methods: Antihypertensive activity was evaluated in normotensive Wistar rats and in animals rendered hypertensive by chronic administration of Nω-nitro-L-arginine methyl ester (L-NAME). Benzaldehyde was administered orally at doses of 20 and 40 mg/kg under both acute (6 h) and subacute (7-day) treatment protocols. Arterial pressure was recorded non-invasively by means of a tail-cuff plethysmography system. Vasorelaxant activity was examined in vitro using isolated rat aortic rings precontracted with either Epinephrine (EP, 10 μM) or potassium chloride (KCl, 80 mM). Endothelium-dependent and endothelium-independent components were dissected by pre-incubating the rings with selective pharmacological inhibitors. Additionally, the effects of benzaldehyde on both phasic and tonic contractions induced by extracellular Ca2+ were assessed in EP-precontracted rings in Ca2+-free Krebs solution. Key Findings: In hypertensive animals, benzaldehyde produced a dose-related decrease in both systolic and diastolic arterial pressure. It induced concentration-dependent vasorelaxation in both endothelium-intact and -denuded aortic rings. Relaxation was also observed in KCl-precontracted rings. Vasorelaxant responses were significantly attenuated by Indomethacin, Nifedipine, and 2-Aminoethoxydiphenyl borinate (2-APB). Significance: These findings demonstrate that benzaldehyde lowers blood pressure through both endothelium-dependent and -independent mechanisms. These include activation of the prostacyclin (PGI2)/cAMP pathway, inhibition of L-type calcium channels, and blockade of store-operated calcium channels (SOCCs).