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Endogenous testosterone increases L-type Ca2+ channel expression in porcine coronary smooth muscle

1 Department of Biomedical Sciences, Center for Gender Physiology and Environmental Adaptation, 2 Veterinary Pathobiology, and 3 Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri 65211 Submitted 15 March 2004 ; accepted in final form 6 July 2004 Evidence indicates tha...

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Published in:American journal of physiology. Heart and circulatory physiology 2004-11, Vol.287 (5), p.H2091-H2098
Main Authors: Bowles, D. K, Maddali, K. K, Ganjam, V. K, Rubin, L. J, Tharp, D. L, Turk, J. R, Heaps, C. L
Format: Article
Language:English
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Summary:1 Department of Biomedical Sciences, Center for Gender Physiology and Environmental Adaptation, 2 Veterinary Pathobiology, and 3 Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri 65211 Submitted 15 March 2004 ; accepted in final form 6 July 2004 Evidence indicates that gender and sex hormonal status influence cardiovascular physiology and pathophysiology. We recently demonstrated increased L-type voltage-gated Ca 2+ current ( I Ca,L ) in coronary arterial smooth muscle (CASM) of male compared with female swine. The promoter region of the L-type voltage-gated Ca 2+ channel (VGCC) (Ca v 1.2) gene contains a hormone response element that is activated by testosterone. Thus the purpose of the present study was to determine whether endogenous testosterone regulates CASM I Ca,L through regulation of VGCC expression and activity. Sexually mature male and female Yucatan swine (7–8 mo; 35–45 kg) were obtained from the breeder. Males were left intact (IM, n = 8), castrated (CM, n = 8), or castrated with testosterone replacement (CMT, n = 8; 10 mg/day Androgel). Females remained gonad intact ( n = 8). In right coronary arteries, both Ca v 1.2 mRNA and protein were greater in IM compared with intact females. Ca v 1.2 mRNA and protein were reduced in CM compared with IM and restored in CMT. In isolated CASM, both peak and steady-state I Ca were reduced in CM compared with IM and restored in CMT. In males, a linear relationship was found between serum testosterone levels and I Ca . In vitro, both testosterone and the nonaromatizable androgen, dihydrotestosterone, increased Ca v 1.2 expression. Furthermore, this effect was blocked by the androgen receptor antagonist cyproterone. We conclude that endogenous testosterone is a primary regulator of Ca v 1.2 expression and activity in coronary arteries of males. voltage clamp; vascular; voltage-gated calcium channels Address for reprint requests and other correspondence: D. K. Bowles, E102 Veterinary Medicine, Univ. of Missouri, Columbia, MO 65211 (E-mail: BowlesD{at}missouri.edu )
ISSN:0363-6135
1522-1539
DOI:10.1152/ajpheart.00258.2004