Deciphering the Mechanisms Behind the Vasodilation and Antihypertensive Properties of a Novel N-Acylhydrazone Derivative

The study introduces a new N-acylhydrazone derivative, LASSBio-1289, synthesized from safrole and investigated for its cardiovascular effects. This compound has been found to possess significant vasodilation and antihypertensive properties. The research involved the use of thoracic aorta and left papillary muscles from both Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) for isometric tension recording.

LASSBio-1289 was observed to induce relaxation in aortic rings from both WKY and SHR, with varying potencies. The compound's vasodilatory activity was augmented in KCl-contracted aortas. It also reduced the contracture induced by calcium in depolarized aortas from both rat strains. The relaxation induced by LASSBio-1289 in endothelium-intact aortas from WKY rats was not affected by various antagonists but was notably reduced by L-NAME and ODQ, suggesting a nitric oxide (NO)/cyclic GMP pathway involvement.

At higher concentrations, LASSBio-1289 decreased the contractility of papillary muscles. Furthermore, acute intravenous injection of LASSBio-1289 induced a significant hypotensive response in SHR, which was also observed during a 14-day administration period via intraperitoneal and oral routes.

The study concludes that LASSBio-1289 promotes both endothelium-independent vasorelaxation through the inhibition of calcium influx via L-type calcium channels and endothelium-dependent relaxation mediated by the NO/cyclic GMP pathway. These findings indicate the potential of LASSBio-1289 as a therapeutic agent for cardiovascular conditions, particularly hypertension.