Unravelling the cardiovascular effects induced by alpha-terpineol: a role for the nitric oxide-cGMP pathway.
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 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 micromol/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 micromol/L l-NAME, 30 micromol/L hydroxocobalamin or 10 micromol/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.
Ribeiro
Thaís P
TP
Laboratory of Pharmaceutical Technology, Federal University of Paraíba, João Pessoa, Brazil.
Porto
Dayanne L
DL
Menezes
Camilla P
CP
Antunes
Alessandra A
AA
Silva
Darízy F
DF
De Sousa
Damião P
DP
Nakao
Lia S
LS
Braga
Valdir A
VA
Medeiros
Isac A
IA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002460:Cell Line; D006152:Cyclic GMP / Q000502:physiology*; D000081005:Cyclohexane Monoterpenes; D053138:Cyclohexenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D039821:Monoterpenes / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*
D002317:Cardiovascular Agents; D000081005:Cyclohexane Monoterpenes; D053138:Cyclohexenes; D004791:Enzyme Inhibitors; D039821:Monoterpenes; C016775:alpha-terpineol; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester