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Vol. 70, No. 1, 2004
Issue release date: January 2004
Pharmacology 2004;70:31–38
(DOI:10.1159/000074240)

Evidence for the Mechanisms Underlying the Effects of Pimaradienoic Acid Isolated from the Roots of Viguiera arenaria on Rat Aorta

Tirapelli C.R. · Ambrosio S.R. · da Costa F.B. · de Oliveira A.M.
aDepartamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo; bDepartamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto; cLaboratório de Farmacognosia, Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto e dLaboratório de Farmacologia, Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Brazil

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Abstract

The present study examines the effects of the diterpene ent-pimara-8(14),15-dien-19-oic acid (PA) on rat thoracic aorta. PA (10–5, 3 × 10–5 and 10–4 mol/l) caused concentration-dependent inhibition of phenylephrine (Phe)-induced contraction in either endothelium-intact or endothelium-denuded aortic rings. PA attenuated the contraction induced by CaCl2 in Ca2+-free solution containing Phe (10–7 mol/l) or KCl (30 mmol/l). This diterpene did not interfere with Ca2+ release from intracellular stores mediated by either Phe (10–6 mol/l) or caffeine (30 mmol/l). PA (10–6 to 3 × 10–4 mol/l) concentration dependently relaxed Phe-pre-contracted rings with intact (92.64 ± 7.60%) or denuded endothelium (98.82 ± 1.56%). Pre-incubation of denuded aortic rings with NG-nitro-L-arginine methyl ester (10–4 mol/l), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10–6 mol/l) or indomethacin (10–5 mol/l) reduced PA-induced relaxation (percentage of relaxation: 77.50 ± 3.95, 78.56 ± 2.81, 77.11 ± 6.22, respectively). However, the relaxant responses induced by PA on Phe-pre-contracted rings were unaffected by tetraethylammonium (1 and 5 mmol/l). PA also relaxed KCl-pre-contracted rings with intact (97.44 ± 3.66%) or denuded endothelium (95.95 ± 3.72%). Collectively, these results support the notion that the effects elicited by PA on vascular smooth muscle are endothelium-independent and involve extracellular Ca2+ influx blocked. In addition, PA effects are partly dependent on the release of nitric oxide from the vascular smooth muscle through an activation of guanylyl cyclase-dependent mechanism and are related to the release of metabolites derived from the arachidonic acid pathway. Finally, our results demonstrated that the PA relaxant action is not related with the opening of potassium (K+) channels.



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References

  1. Cheung HT, Fu SL, Smal MA: Inhibition of platelet aggregation by diterpenes acids from Pinus massoniana resin. Arzneimittelforschung 1994;44:17–25.
  2. Ulubelen A, Topcu G, Johansson CB: Norditerpenoids and diterpenoids from Salvia multicaulis with antituberculous activity. J Nat Prod 1997;60:1275–1280.
  3. Suh YG, Kim YH, Park MH, Choi YH, Lee HK, Moon JY, Min KH, Shin DY, Jung JK, Park OH, Jeon RO, Park HS, Kang SA: Pimarane cyclooxygenase 2 (COX-2) inhibitor and its structure-activity relationship. Bioorg Med Chem Lett 2001;11:559–562.
  4. Ohashi K, Bohgaki T, Matsubara T, Shibuya H: Indonesian medicinal plants. XXIII. Chemical structures of two new migrated pimarane-type diterpenes, neoorthosiphols A and B, and suppressive effects on rat thoracic aorta of chemical constituents isolated from the leaves of Orthosiphon aristatus (Lamiaceae). Chem Pharm Bull 2000;48:433–435.
  5. Ambrosio SR, Tirapelli CR, Bonaventura D, De Oliveira AM, Da Costa FB: Pimarane diterpene from Viguiera arenaria (Asteraceae) inhibit rat carotid contraction. Fitoterapia 2002;73:484–489.
  6. Shibata S, Mihashi S, Tanaka O: The occurrence of (–)-pimarane-type diterpene in Aralia cordata Thumb. Tetrahedron Lett 1967;51:5241–5243.

    External Resources

  7. Matsuo A, Uto S, Nakayama M, Hayashi S: (–)-Thermarol, a new ent-pimarane-class diterpene diol from Jungermania thermarum (liverwort). Tetrahedron Lett 1976;28:2451–2454.
  8. Furchgott RF, Zawadzki JV: The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980;288:373–376.
  9. David FL, Montezano ACI, Rebouças NA, Nigro D, Fortes ZB, Carvalho MHC, Tostes RCA: Gender differences in vascular expression of endothelin and ETA/ETB receptors, but not in calcium-handling mechanisms, in deoxycorticosterone acetate-salt hypertension. Braz J Med Biol Res 2002;35:1061–1068.
  10. Eckert RE, Karsten AJ, Utz J, Ziegler M: Regulation of renal artery smooth muscle tone by α1-adrenoceptors: Role of voltage-gated calcium channels and intracellular calcium stores. Urol Res 2000;28:122–127.
  11. Leitjen PAA, van Breemen C: The effects of caffeine on the noradrenaline-sensitive Ca2+ store in rabbit aorta. J Physiol 1984;357:327–339.
  12. Hudgins A, Weiss G: Effects of calcium removal upon vascular smooth muscle contraction induced by norepinephrine, histamine and potassium. J Pharm Exp Ther 1968;159:91–97.
  13. Hirata S, Enoki T, Kitamura R, Vinh VH, Nakamura K, Mori K: Effects of isoflurane on receptor-operated Ca2+ channels in rat aortic smooth muscle. Br J Anesth 1998;81:578–583.
  14. Gibson A, Pollock D: The effects of drugs on the sensitivity of the rat anococcygeus muscle to agonists. Br J Pharmacol 1973;49:506–513.
  15. Moncada S, Palmer RMJ, Higgs EA: Nitric oxide: Physiology, pathophysiology and pharmacology. Pharmacol Rev 1991;43:109–142.
  16. Robertson BE, Schubert R, Hescheler J, Nelson MT: cGMP-dependent protein kinase activates Ca-activated K channels in cerebral artery smooth muscle cells. Am J Physiol 1993;265:C299–C303.
  17. Garthwaite J, Southam E, Boulton CL, Nielsen EB, Schmidt K, Mayer B: Potent and selective inhibition of nitric oxide-sensitive guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. Mol Pharmacol 1995;48:184–188.
  18. Hamilton TC, Weston AH: Cromakalim, nicorandil and pinacidil: Novel drugs which open potassium channels in smooth muscle. Gen Pharmacol 1989;20:1–9.
  19. Nelson MT, Quayle JM: Physiological roles and properties of potassium channels in arterial smooth muscle. Am J Physiol 1995;268:C799–C822.


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