Several new bioactive compounds of the N-acylhydrazone class were developed from the safrole, a Brazilian natural product obtained from sassafras oil (Ocotea pretiosa).

This work investigated the effects on cardiovascular system of LASSBio-897, a new analogue of the lead compound 3,4-methylenedioxybenzoyl-2-thienylhydrazone named LASSBio-294.

Thoracic aorta from Wistar–Kyoto (WKY) rats was prepared for isometric tension recording and for cGMP content determination.

• Blood pressure (BP) was measured in WKY rats and spontaneously hypertensive rats (SHR)
• after treatment with 1 mg/kg intravenously of LASSBio-897 and during 14 days' treatment of SHR with 1 mg/kg/day perorally.

LASSBio-897 (0.05–1 µmol/l) exhibited a potent vasodilatory activity in phenylephrine (Phe)-contracted aortic rings from WKY rats.

This effect was abolished in endothelium-denuded aortic rings and after treatment with the nitric oxide (NO) synthase inhibitor, N^G-nitro-L-arginine methyl ester (L-NAME) or the guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ).

Also, LASSBio 897 (1 µmol/l) increased about 15 times the intracellular content of cGMP.

LASSBio-897-induced vasodilation was totally inhibited by the muscarinic antagonist atropine and by the M₃ subtype selective antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), indicating the involvement of M₃ receptors.

Intravenous administration of LASSBio-897 (1 mg/kg) produced significant hypotensive response in both WKY and SHR. The hypotensive effect of LASSBio-897 was also observed during the 14 days of oral administration.

The novel N-acylhydrazone derivative LASSBio-897 exhibited a potent vasodilatory activity in aortic rings mediated by the NO/cGMP pathway via activation of endothelial M₃ receptors and was orally effective in reducing BP on SHR.

American Journal of Hypertension 2010; doi:10.1038/ajh.2009.238

Gisele Zapata-Sudo¹, Sharlene L. Pereira¹, Hellen J.V. Beiral¹, Arthur E. Kummerle^2,3, Juliana M. Raimundo¹, Fernanda Antunes⁴, Roberto T. Sudo¹, Eliezer J. Barreiro^2,3 and Carlos A.M. Fraga^2,3

• ¹Programa de Desenvolvimento de Fármacos, Departamento de Farmacologia Basica e Clinica, ICB, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
• ²Programa de Pós-Graduação em Química, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
• ³Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
• ⁴Laboratório de Sanidade Animal, Universidade Estadual Norte Fluminense Darcy Ribeiro, Campos, Brazil

Correspondence: Gisele Zapata-Sudo, (gsudo@farmaco.ufrj.br)