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Research ArticleCARDIOVASCULAR

Enhanced Responses to 17β-Estradiol in Rat Hearts Treated with Isoproterenol: Involvement of a Cyclic AMP-Dependent Pathway

Hong-Yu Li, Jin-Song Bian, Yiu Wa Kwan and Tak Ming Wong
Journal of Pharmacology and Experimental Therapeutics May 2000, 293 (2) 592-598;
Hong-Yu Li
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Jin-Song Bian
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Yiu Wa Kwan
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Tak Ming Wong
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Abstract

We determined the effects of 17β-estradiol, the most effective estrogen, acutely administered, on the heart/ventricular myocyte with or without treatment with isoproterenol (Iso). At 0.1 to 1 nM, 17β-estradiol, which itself had no effect, reduced the heart rate and developed pressures in the isolated perfused heart treated with 10−7 M Iso. One nanomolar 17β-estradiol also inhibited the cyclic AMP (cAMP) production in Iso-treated ventricular myocytes. At 10 nM to 1 μM, 17β-estradiol itself reduced the heart rate and incidence of ischemia/reperfusion-induced arrhythmias, with the exception of diastolic pressure. The effects of 17β-estradiol on heart rate, systolic and mean pressures, and arrhythmias were significantly enhanced in the heart/ventricular myocyte treated with Iso. Tamoxifen, an estrogen receptor antagonist, did not antagonize the effect of 17β-estradiol on the Ca2+ current in ventricular myocytes treated with Iso, nor did it alter the effect of the hormone on the cAMP production augmented by Iso and forskolin. The effects of 17β-estradiol on Ca2+ current in the presence or absence of tamoxifen and/or Iso were similar in male rats, which do not possess the estrogen receptor, and female rats, which have the estrogen receptor. In conclusion, we have shown for the first time that estrogen at physiological concentrations modulates negatively the stimulatory actions of Iso on the heart rate and cardiac contractility. The effects may result from activation of an unknown membrane receptor and the adenylate cyclase/cAMP pathway, which enhances Ca2+influx across the L-type Ca2+ channel.

Footnotes

  • Send reprint requests to: Tak Ming Wong, Ph.D., Department of Physiology, Faculty of Medicine, The University of Hong Kong, Li Shu Fan Bldg., Sassoon Rd., Hong Kong, China. E-mail:wongtakm{at}hkucc.hku.hk

  • ↵1 This study was supported by the Committee of Research and Conference Grants, The University of Hong Kong to T.M.W., and National Natural Science Foundation of China Grant 39770323 to H.-Y.L.

  • 2 H.-Y.L. and J.-S.B. were on leave from the Western China University of Medical Sciences and Nanjing Medical University, respectively.

  • Abbreviations:
    Iso
    isoproterenol
    AC
    adenylate cyclase
    cAMP
    cyclic AMP
    KB
    Kraftebruhe
    DMSO
    dimethylsulfoxide
    • Received September 16, 1999.
    • Accepted January 19, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 293 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 293, Issue 2
1 May 2000
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Research ArticleCARDIOVASCULAR

Enhanced Responses to 17β-Estradiol in Rat Hearts Treated with Isoproterenol: Involvement of a Cyclic AMP-Dependent Pathway

Hong-Yu Li, Jin-Song Bian, Yiu Wa Kwan and Tak Ming Wong
Journal of Pharmacology and Experimental Therapeutics May 1, 2000, 293 (2) 592-598;

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Research ArticleCARDIOVASCULAR

Enhanced Responses to 17β-Estradiol in Rat Hearts Treated with Isoproterenol: Involvement of a Cyclic AMP-Dependent Pathway

Hong-Yu Li, Jin-Song Bian, Yiu Wa Kwan and Tak Ming Wong
Journal of Pharmacology and Experimental Therapeutics May 1, 2000, 293 (2) 592-598;
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