Estudo da atividade cardiovascular do a-terpineol em ratos : abordagens in vivo e in vitro

Abstract

The essential oils are volatiles organic constituents found in aromatic plants, which present several monoterpenes. a-terpineol is an important chemical constituent of the essential oil of many plants.. Studies have demonstrated some biologic activities such as antifungal and antispasmodic. In the present work the cardiovascular effects of a-terpineol were investigated in normotensive rats. Male Wistar rats (250-350 g) were anaesthetized and polyethylene catheters were inserted into the low abdominal aorta and inferior vena cava for blood pressure measurements and administration of drugs. Arterial pressure and heart rate were measured by using a pressure transducers coupled to a computer set and CVMS software. Isolated superior mesenteric rings (1-2 mm) were suspended by cotton threads for isometric tension recordings in Tyrode s solution (37°C, gassed with 95% O2 and 5% CO2), under 0.75g resting tension. In normotensive non-anaesthetized rats (n=6), a-terpineol (1, 5, 10, 20, 30 mg/Kg i.v., randomly) injections produced hypotension (-8,6 ± 2,25; - 18,35 ± 4,35; -33,25±6,0; -51,2±4,5 e -49,5±6,5 mmHg, n=6 , respectively followed by tachycardia (44,6±5,3; 24,5±8,4; 109,8±7,3; 113,2±12,4 e 35,8±14,0 bpm, n=6, respectively). However, hypotensive and tachycardic responses were significantly attenuated after L-NAME (20 mg/Kg ,i.v.) administration i.v (-1,5±0,6; -4,9±2,0; - 6,9±2,8; -22,0±9,0 e -22,1±9,0 mmHg, n=4). In intact isolated rat mesenteric rings a- terpineol (10-12 10-5M) induced concentration-dependent relaxation of the contractions induced by phylephrine (10μM) [Emax=62.41±13.79%]. After endothelium removal the vasorelaxant elicited by a-terpineol was significantly attenuated [Emax= 20.08±4.95]. Similar results were obtained in the presence LNAME 100 or 300 μM, a competitive antagonist of NOS, hydroxocobalamin 30 μM, a NO scavenger or ODQ 10μM, a selective inhibitor of soluble guanylyl cyclase [Emax= 18.33± 3.85% Emax= 23.24± 3.93% Emax= 23.49±7.05 Emax= 20.79 ± 1.06% respectively, p<0,001]. Furthermore, vasorelaxation was significantly attenuated in the presence of 20 mM KCl a modulator K+ efflux [Emax=23.07±14.36%] or several blocking of potassium channels: 1mM 4-aminopirimidine [Emax=26.48±10.50 %], 10 μM glibenclamide [Emax=27.97±3.7%], was not significantly modified after 1 mM tetraethylammonium [Emax=55.40±17.56%]. In conclusion, the present study demonstrated that a-terpineol induced hypotensive effect, probably due to a decrease of peripheral vascular resistances, which seems to be mediated by endothelium derived relaxant factors, at least NO.induced. These results suggest that vasorelaxant response, almost completely mediated by the endothelium, likely via NO release and activation of NO-cGMP pathway and consequently by potassium channels activation at least, KV, and KATP are involved in the vasorelaxant effect induced by a-terpineol.