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Planta Med 2002; 68(9): 784-789
DOI: 10.1055/s-2002-34443
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

Kavain Attenuates Vascular Contractility Through Inhibition of Calcium Channels

Hugh B. Martin1 , Michael McCallum1 , William D. Stofer1 , Mark R. Eichinger2
  • 1Department of Anesthesiology, University of New Mexico Health Sciences Center Albuquerque, N.M., U.S.A.
  • 2Department of Pediatrics, University of New Mexico Health Sciences Center, Albuquerque, N.M., U.S.A.
Further Information

Publication History

Received: December 28, 2001

Accepted: March 29, 2002

Publication Date:
30 September 2002 (online)

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Abstract

Kavain is a biologically active compound from the Oceanic plant Piper methysticum (kava). Traditional medicinal uses of the kava root are many. Kava is increasingly being utilized by Western societies for its anxiolytic effects. Recent reports indicate that kavain blocks ion channels in neural tissue, relaxes precontracted ileum, and relaxes precontracted airway. Thus, we investigated the potential ability of this plant-derived compound to alter vascular smooth muscle function. Thoracic aortae were isolated from Sprague-Dawley rat and cut into 4 mm rings. Rings were placed in tissue baths and suspended from force-displacement transducers for the measurement of isometric tension. In a dose-dependent manner, kavain (10-6 M to 10-3 M) was found to relax aortic rings precontracted with phenylephrine (PE). This response was not dependent on functional endothelium. In addition, kavain pretreatment (3 × 10-5 M or 3 × 10-4 M) attenuated vascular smooth muscle contraction evoked by PE. However, kavain failed to attenuate PE-mediated contraction in calcium (Ca++)-free buffer, indicating that intracellular signaling processes were likely not affected. Also, kavain did attenuate the contraction elicited by administration of Ca++ to depolarized tissue. Interestingly, in rings pre-treated with the selective L-type Ca++ channel blocker nifedipine, kavain-mediated relaxation was inhibited. Lastly, in rings selectively contracted with an L-type calcium channel activator, kavain elicited dose-dependent (and ultimately complete) relaxation. These data strongly suggest that kavain impairs vascular smooth muscle contraction, likely through inhibition of Ca++ channels.

Key words

Kavain - rat - aortae - nifedipine - Piper methysticum - Piperaceae

References

  • 1 Cawte J. Psychoactive substances of the South Seas: betel, kava and pituri.  Australian and New Zealand Journal of Psychiatry. 1985;  19 83-7
    PubMedGoogle Scholar
  • 2 Schirrmacher K, Busselberg D, Langosch J M, Walden J, Winter U, Bingmann D. Effects of (+/-)-kavain on voltage-activated inward currents of dorsal root ganglion cells from neonatal rats.  European Neuropsychopharmacology. 1999;  9 171-6
    PubMedGoogle Scholar
  • 3 Jamieson D D, Duffield P H. The antinociceptive actions of kava components in mice.  Clinical and Experimental Pharmacology and Physiology. 1990;  17 495-507
    PubMedGoogle Scholar
  • 4 Martin H B, Stofer W D, Eichinger M R. Kavain inhibits murine airway smooth muscle contraction.  Planta Medica. 2000;  66 601-6
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Seitz U, Ameri A, Pelzer H, Gleitz J, Peters T. Relaxation of evoked contractile activity of isolated guinea-pig ileum by (+/-)-kavain.  Planta Medica. 1997;  63 303-6
    PubMedGoogle Scholar
  • 6 Kanagy N L, Webb R C. Increased responsiveness and decreased expression of G proteins in deoxycorticosterone hypertension.  Hypertension. 1996;  27 740-5
    PubMedGoogle Scholar
  • 7 DeLean A, Munson P, Robard D. Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose response curves.  American Journal of Physiology. 1978;  4 E97-102
    PubMedGoogle Scholar
  • 8 Friese J, Gleitz J. Kavain, dihydrokavain, and dihydromethysticin non-competitively inhibit the specific binding of [3 H]-batrachotoxinin-A 20-alpha-benzoate to receptor site 2 of voltage-gated Na+ channels.  Planta Medica. 1998;  64 458-9
    PubMedGoogle Scholar
  • 9 Gleitz J, Beile A, Peters T. (+/-)-Kavain inhibits veratridine-activated voltage-dependent Na+-channels in synaptosomes prepared from rat cerebral cortex.  Neuropharmacology. 1995;  4 1133-8
    PubMedGoogle Scholar
  • 10 Magura E I, Kopanitsa M V, Gleitz J, Peters T, Krishtal O A. Kava extract ingredients, (+)-methysticin and (+/-)-kavain inhibit voltage-operated Na+-channels in rat CA1 hippocampal neurons [published erratum: appears in Neuroscience. 1998; 84(1):323].  Neuroscience. 1997;  81 345-51
    CrossrefPubMedGoogle Scholar
  • 11 Liu S J, Kennedy R H. α1-adrenergic activation of L-type Ca current in rat ventricular myocytes: perforated patch-clamp recordings.  American Journal of Physiology. 1998;  274 H2203-7
    PubMedGoogle Scholar
  • 12 Graham R M, Perez D M, Hwa J, Piascik M T. α1-adrenergic receptor subtypes.  Circulation Research. 1996;  78 737-49
    PubMedGoogle Scholar
  • 13 Eckert R E, Karsten A J, Utz J, Ziegler M. Regulation of renal artery smooth muscle tone by α1-adrenoceptors: role of voltage-gated calcium channels and intracellular calcium stores.  Urology Research. 2000;  28 122-7
    PubMedGoogle Scholar

Mark R. Eichinger, Ph. D.

Department of Pediatrics

University of New Mexico Health Sciences Center

2211 Lomas Blvd. NE/ ACC, 3rd Floor

Albuquerque, New Mexico 87131-5311, U.S.A.

Fax: +505-272-6845

Email: meichinger@salud.unm.edu

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