title: The new nitric oxide donor cyclohexane nitrate induces vasorelaxation, hypotension, and antihypertensive effects via NO/cGMP/PKG pathway.
abstract: We investigated the cardiovascular effects induced by the nitric oxide donor Cyclohexane Nitrate (HEX). Vasodilatation, NO release and the effects of acute or sub-chronic treatment with HEX on cardiovascular parameters were evaluated. HEX induced endothelium-independent vasodilatation (Maximum effect [efficacy, ME] = 100.4 ± 4.1%; potency [pD2] = 5.1 ± 0.1). Relaxation was attenuated by scavenging nitric oxide (ME = 44.9 ± 9.4% vs. 100.4 ± 4.1%) or by inhibiting the soluble guanylyl cyclase (ME = 38.5 ± 9.7% vs. 100.4 ± 4.1%). In addition, pD2 was decreased after non-selective blockade of K(+) channels (pD2 = 3.6 ± 0.1 vs. 5.1 ± 0.1) or by inhibiting KATP channels (pD2 = 4.3 ± 0.1 vs. 5.1 ± 0.1). HEX increased NO levels in mesenteric arteries (33.2 ± 2.3 vs. 10.7 ± 0.2 au, p < 0.0001). Intravenous acute administration of HEX (1-20 mg/kg) induced hypotension and bradycardia in normotensive and hypertensive rats. Furthermore, starting at 6 weeks after the induction of 2K1C hypertension, oral treatment with the HEX (10 mg/Kg/day) for 7 days reduced blood pressure in hypertensive animals (134 ± 6 vs. 170 ± 4 mmHg, respectively). Our data demonstrate that HEX is a NO donor able to produce vasodilatation via NO/cGMP/PKG pathway and activation of the ATP-sensitive K(+) channels. Furthermore, HEX acutely reduces blood pressure and heart rate as well as produces antihypertensive effect in renovascular hypertensive rats.
authors.affiliation: Biotechnology Center, Federal University of Paraíba João Pessoa, Brazil.
authors.forename: Leônidas das G
authors.initials: Ld
authors.lastname: Mendes-Júnior
authors.affiliation: Biotechnology Center, Federal University of Paraíba João Pessoa, Brazil.
authors.forename: Driele D
authors.initials: DD
authors.lastname: Guimarães
authors.affiliation: Biotechnology Center, Federal University of Paraíba João Pessoa, Brazil.
authors.forename: Danilo D A
authors.initials: DD
authors.lastname: Gadelha
authors.affiliation: Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais Belo Horizonte, Brazil.
authors.forename: Thiago F
authors.initials: TF
authors.lastname: Diniz
authors.affiliation: Department of Chemistry, Federal University of Paraíba João Pessoa, Brazil.
authors.forename: Maria C R
authors.initials: MC
authors.lastname: Brandão
authors.affiliation: Department of Chemistry, Federal University of Paraíba João Pessoa, Brazil.
authors.forename: Petrônio F
authors.initials: PF
authors.lastname: Athayde-Filho
authors.affiliation: Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais Belo Horizonte, Brazil.
authors.forename: Virginia S
authors.initials: VS
authors.lastname: Lemos
authors.affiliation: Biotechnology Center, Federal University of Paraíba João Pessoa, Brazil.
authors.forename: Maria do S
authors.initials: Mdo S
authors.lastname: França-Silva
authors.affiliation: Biotechnology Center, Federal University of Paraíba João Pessoa, Brazil.
authors.forename: Valdir A
authors.initials: VA
authors.lastname: Braga
keywords: KATP channels; hypertension; mesenteric artery; nitric oxide; nitric oxide donors