Involvement of Nitric Oxide in the Mediation of the Hypotensive Action of the Essential Oil of Mentha × villosa in Normotensive Conscious Rats

Abstract

Recently, we showed that intravenous (i.v.) treatment with the essential oil of Mentha × villosa (EOMV) in pentobarbitone-anaesthetised rats decreased blood pressure; the effect occurred independently of the presence of an operational central autonomic drive to the cardiovascular system. This finding suggested that the hypotensive activity of EOMV may result from its vasodilatory effects directly upon vascular smooth muscle. The present study examines this possibility and whether EOMV-induced hypotension is mediated, at least in part, by an endothelial L-arginine/nitric oxide pathway. In conscious rats, i.v. injections of bolus doses (1 to 20 mg/kg) of EOMV elicited immediate and dose-dependent decreases in mean aortic pressure (MAP) and heart rate (HR). Pretreatment with i.v. hexamethonium (30 mg/kg) reduced the EOMV-induced bradycardia without affecting the hypotension. However, i.v. pretreatment with the nitric oxide synthase inhibitor, N ^G-nitro-L-arginine methyl (L-NAME, 20 mg/kg), reduced partially, but significantly, the maximal percent decreases in MAP elicited by EOMV without affecting the bradycardia. In rat isolated thoracic aorta preparations, EOMV (1 - 130 μg/ml) induced a concentration-dependent reduction of potassium (60 mM)-induced contraction. This smooth muscle-relaxant activity of EOMV was significantly reduced by the incubation of endothelium-intact rings with L-NAME (20 μM), as evidenced by the significant enhancement in the IC₅₀ for EOMV-induced reduction of potassium-induced contraction (133.8 ± 26.5 vs. 65.2 ± 8.2 μg/ml in the absence of L-NAME). Furthermore, the vasorelaxant effects of EOMV in endothelium-denuded aortic rings were also significantly reduced (IC₅₀ = 109 ± 10 μg/ml), compared to those observed in segments with intact endothelium (IC₅₀ = 61 ± 13 μg/ml). These results show that i.v. treatment with EOMV dose-dependently decreases blood pressure in conscious rats, and that this action is due to an active vascular relaxation rather than withdrawal of sympathetic tone. Released nitric oxide from vascular endothelial cells appears partially involved in the aortic relaxation induced by EOMV and in turn in the mediation of EOMV-induced hypotension. They further support the concept that EOMV-induced hypotension and bradycardia occurred independently.

Key words

Mentha × villosa - Labiatae - essential oil - cardiovascular effects - nitric oxide - isolated thoracic aorta - conscious rat

References

• 1 Matos F JA. Farmácias vivas. 3^a edição. Ed. by Edicões UFC, Fortaleza CE Brazil; 2001
• 2 Borba M OP, Silva J F, Montenegro L, Jugmann O, Cavalcanti M M, Albuquerque P MS. Frações ativas da Mentha crispa sobre camundongos albinos Swiss infectados com Schistosoma mansoni cepa São Lourenço da Mata.  In: XI Simpósio de Plantas Medicinais do Brasil, João Pessoa. PB Brazil; 1990: pp. 49
• 3 Melo A M, Pinho S, Santana C F, Santos E R, Souza I A. Primeiras observações sobre o uso da Mentha crispa em tricomoníase urogenital.  In: XI Simpósio de Plantas Medicinais de Brasil, Curitiba. PR Brazil; 1992: pp. 160
• 4 Santana C F, Almeida E R, dos Santos E R, Souza I A. Actions of Mentha crispa hydroethanolic extract in patients bearing intestinal protozoan.  Fitoterapia. 1992;  63 409-10
• 5 Hiruma C A. Estudo químico e farmacológico do óleo essencial das folhas de Mentha × villosa Hudson. Master Thesis. Departamento de Fisiologia e Farmacologia, Universidade Federal de Paraíba 1993 João Pessoa, PB, Brazil;
• 6 Matos F JA, Machado M IL, Craveiro A A, Alencar J W, Barbosa J M, da Cunhã E VL, Hiruma C A. Essential oil of Mentha × villosa Huds. from northeastern Brazil.  Journal of Essential Oil Research. 1999;  11 41-4
• 7 Sousa P JC, Magalhães P JC, Lima C C, Oliveira V S, Leal-Cardoso J H. Effects of piperitenone oxide on the intestinal smooth muscle of the guinea pig.  Brazilian Journal of Medical and Biological Research. 1997;  30 787-91
• 8 Sousa P JC. Estudo Farmacológico de óleo essencial de Mentha × villosa e seu principal constituinte, óxido de piperitenona, em músculos lisos gastrointestinais de cobaia e pressão arterial de rato. Doctoral Thesis. Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará 1999 Fortaleza, CE, Brazil;
• 9 Lahlou S, Carneiro-Filho R FL, Leal-Cardoso J H, Toscano C F. Cardiovascular effects of the essential oil of Mentha × villosa and its main constituent, piperitenone oxide, in normotensive anaesthetised rats: role of the autonomic nervous system.  Planta Medica. 2001;  67 638-43
• 10 Lahlou S, Leal-Caredoso J H, Magalhães P JC. Essential oil of Croton nepetaefolius decreases blood pressure through an action upon vascular smooth muscle: studies in DOCA-salt hypertensive rats.  Planta Medica. 2000;  66 138-43
• 11 Craveiro A A, Matos F JA, Alencar J W. Simple and inexpensive steam-generator for essential oils extraction.  Journal of Chemical Education. 1976;  53 562
• 12 Degouville A CL, Cavero I. Cross tachyphylaxis to endothelin isopeptide-induced hypotension. A phenomenon not seen with proendothelin.  British Journal of Pharmacology. 1991;  104 77-84
• 13 Sapru H N, Gonzalez E R, Krieger A J. Greater splanchnic nerve activity in the rat.  Brain Research Bulletin. 1982;  8 267-72
• 14 Boussairi H, Sassard J. Cardiovascular effects of basic fibroblast growth factor in rats.  Journal of Cardiovascular Pharmacology. 1994;  23 99-102
• 15 Lahlou S, Leal-Cardoso J H, Magalhães P JC, Coelho-de-Souza A N, Pinto Duarte G. Cardiovascular effects of the essential oil of Croton nepetaefolius in rats: role of the autonomic nervous system.  Planta Medica. 1999;  65 553-7
• 16 Fruchgott R F, Zawadzki J V. The obligatory role of endothelial-cells in the relaxation of arterial smooth-muscle by acetylcholine.  Nature. 1980;  288 373-6
• 17 Leal-Cardoso J H, Fonteles M C. Pharmacological effects of essential oils of plants of the northeast of Brazil.  Anais da Academia Brasileira de Ciências. 1999;  71 201-13
• 18 Fogaça R TH, Cavalcante A DA, Serpa A KL, Souza P JC, Coelho-de-Souza A N, Leal-Cardoso J H. The effects of essential oil of Mentha × villosa on skeletal muscle of the toad.  Phytotherapy Research. 1997;  11 552-7
• 19 Jiang M J, Morgan K G. Intracellular calcium levels in phorbol ester-induced contractions of vascular muscle.  American Journal of Physiology. 1987;  253 H1365-71
• 20 Litten R Z, Suba E A, Roth B L. Effects of a phorbol ester on rat aortic contraction and calcium influx in the presence and absence of BAY k 8644.  European Journal of Pharmacology. 1987;  144 185-91