Unravelling the cardiovascular effects induced by alpha-terpineol: A role for the nitric oxide-cGMP pathway

作者：Ribeiro Thais P; Porto Dayanne L; Menezes Camilla P; Antunes Alessandra A; Silva Darizy F; De Sousa Damiao P; Nakao Lia S; Braga Valdir A; Medeiros Isac A^*

来源：Clinical and Experimental Pharmacology and Physiology, 2010, 37(8): 811-816.

DOI：10.1111/j.1440-1681.2010.05383.x

• hypotension
• monoterpene
• nitric oxide
• rabbit aorta endothelial cells
• vasodilatation

P>1. alpha-Terpineol is a monoterpene found in the essential oils of several aromatic plant species. In the present study, we investigated the mechanisms underlying the cardiovascular changes induced by alpha-terpineol in rats.
2. In normotensive rats, administration of alpha-terpineol (1, 5, 10, 20 and 30 mg/kg, i.v.) produced a dose-dependent hypotension (-10 +/- 3, -20 +/- 8, -39 +/- 16, -52 +/- 21 and -57 +/- 23 mmHg, respectively; n = 5) followed by tachycardia. The hypotensive responses to 1, 5, 10, 20 and 30 mg/kg, i.v., alpha-terpineol were significantly attenuated following the administration of NG-nitro-l-arginine methyl ester (l-NAME; 20 mg/kg, i.v.; -2 +/- 1, -5 +/- 2, -7 +/- 3, -22 +/- 9 and -22 +/- 10 mmHg, respectively; P < 0.05; n = 5).
3. In 10 mu mol/L phenylephrine (PE)-precontracted mesenteric artery rings, alpha-terpineol (10-12 to 10-5 mol/L) caused a concentration-dependent relaxation (maximum relaxation 61 +/- 6%; n = 7). After removal of the endothelium, the vasorelaxation elicited by alpha-terpineol was attenuated (maximum relaxation 20 +/- 1%; P < 0.05; n = 7). In addition, vasorelaxation induced by alpha-terpineol in rings pretreated with 100 or 300 mu mol/L l-NAME, 30 mu mol/L hydroxocobalamin or 10 mu mol/L 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one was attenuated (maximum relaxation 18 +/- 3, 23 +/- 3, 24 +/- 7 and 21 +/- 1%, respectively; n = 6; P < 0.05).
4. Furthermore, in a rabbit aortic endothelial cell line, 10-6, 10-5 and 10-4 mol/L alpha-terpineol induced concentration-dependent increases in nitric oxide (NO) levels (12 +/- 6, 18 +/- 9 and 34 +/- 12%Delta fluorescence, respectively; n = 3).
5. In conclusion, using combined functional and biochemical approaches in the present study, we were able to demonstrate that alpha-terpineol-induced hypotension and vasorelaxation are mediated, at least in part, by the endothelium, most likely via NO release and activation of the NO-cGMP pathway.

• 出版日期2010-8