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Unravelling the cardiovascular effects induced by α‐terpineol: A role for the nitric oxide–cGMP pathway
Author(s) -
Ribeiro Thaís P,
Porto Dayanne L,
Menezes Camilla P,
Antunes Alessandra A,
Silva Darízy F,
De Sousa Damião P,
Nakao Lia S,
Braga Valdir A,
Medeiros Isac A
Publication year - 2010
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2010.05383.x
Subject(s) - terpineol , chemistry , hydroxocobalamin , nitric oxide , phenylephrine , pharmacology , stereochemistry , endocrinology , biochemistry , chromatography , medicine , blood pressure , organic chemistry , cyanocobalamin , vitamin b12
Summary 1. α‐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 α‐terpineol in rats. 2. In normotensive rats, administration of α‐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., α‐terpineol were significantly attenuated following the administration of N G ‐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 μmol/L phenylephrine (PE)‐precontracted mesenteric artery rings, α‐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 α‐terpineol was attenuated (maximum relaxation 20 ± 1%; P < 0.05; n = 7). In addition, vasorelaxation induced by α‐terpineol in rings pretreated with 100 or 300 μmol/L l ‐NAME, 30 μmol/L hydroxocobalamin or 10 μmol/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 α‐terpineol induced concentration‐dependent increases in nitric oxide (NO) levels (12 ± 6, 18 ± 9 and 34 ± 12%Δ fluorescence, respectively; n = 3). 5. In conclusion, using combined functional and biochemical approaches in the present study, we were able to demonstrate that α‐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.