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

Abstract

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.

• Authors: Thaís P Ribeiro, Dayanne L Porto, Camilla P Menezes, Alessandra A Antunes, Darízy F Silva, Damião P De Sousa, Lia S Nakao, Valdir A Braga, Isac A Medeiros
• Journal: Clinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 37 Issue 8 Pg. 811-6 (Aug 2010) ISSN: 1440-1681 [Electronic] Australia
• PMID: 20374260 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiovascular Agents
• Cyclohexane Monoterpenes
• Cyclohexenes
• Enzyme Inhibitors
• Monoterpenes
• alpha-terpineol
• Nitric Oxide
• Nitric Oxide Synthase Type III
• Cyclic GMP
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Blood Pressure (drug effects)
• Cardiovascular Agents (pharmacology)
• Cell Line
• Cyclic GMP (physiology)
• Cyclohexane Monoterpenes
• Cyclohexenes (pharmacology)
• Dose-Response Relationship, Drug
• Endothelial Cells (drug effects, metabolism)
• Enzyme Inhibitors (pharmacology)
• Heart Rate (drug effects)
• In Vitro Techniques
• Male
• Mesenteric Arteries (drug effects)
• Monoterpenes (pharmacology)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide (physiology)
• Nitric Oxide Synthase Type III (antagonists & inhibitors)
• Rats
• Rats, Wistar
• Signal Transduction (drug effects)