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1 Department of Biomedical Sciences, University of Missouri, Columbia, Missouri, USA; Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, USA
2 Department of Biomedical Sciences, University of Missouri, Columbia, Missouri, USA
3 Department of Biomedical Sciences, University of Missouri, Columbia, Missouri, USA; Veterinary Pathobiology, University of Missouri, Columbia, Missouri, USA
* To whom correspondence should be addressed. E-mail: bowlesd{at}missouri.edu.
Evidence indicates that sex and sex hormonal status influence cardiovascular physiology and pathophysiology. We recently demonstrated increased L-type voltage-gated Ca2+ current (ICa) in coronary artery smooth muscle (CASM) of male compared to female swine. The promoter region of the L-type VGCC (Cav1.2) gene contains a hormone response element which is activated by testosterone (T). Thus, the purpose of the present study was to determine if endogenous T regulates CASM L-type ICa through regulation of VGCC expression and activity. Sexually mature male and female Yucatan swine (7-8 months; 35-45 kg) were obtained from the breeder. Males were left intact (IM, n=8), castrated (CM, n=8) or castrated with T replacement (CMT, n=8; Androgel, 10 mg/day). Females remained gonad-intact (IF, n=8). In right coronary arteries (RCA), both Cav1.2 mRNA and protein were greater in IM compared to IF. Cav1.2 mRNA and protein were reduced in CM compared to IM and restored in CMT. In isolated CASM, both peak and steady-state ICa were reduced in CM compared to IM and restored in CMT. In males, a linear relationship was found between serum T levels and ICa. In vitro, both T and the non-aromatizable androgen, dihydrotestosterone (DHT) increased Cav1.2 expression. Furthermore, this effect was blocked by the androgen receptor antagonist, cyproterone. We conclude that endogenous T is a primary regulator of Cav1.2 expression and activity in coronary arteries of males.
This article has been cited by other articles:
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