Testosterone decreases myocardial ischaemia in men with coronary artery disease via a coronary vasodilatory action. However, long-term therapy may increase the risk of prostatic carcinoma via activation of the nuclear AR (androgen receptor). In the present study, we have investigated the mechanism of testosterone-induced vasodilatation using isolated rat coronary arteries and thoracic aortae from control and AR-deficient testicular-feminized mice. Vasodilatation induced by testosterone, T-3-OCMO [testosterone 3-(O-carboxymethyl)oxime] or T-3-OCMO conjugated to BSA was initially measured in preconstricted vessels that had undergone endothelial denudation or incubation with flutamide (10 μM). Cellular fluorescence was also measured in primary aortic SMCs (smooth muscle cells) following exposure to the above fluorescent-labelled agents. Subsequently, vessels were incubated with testosterone (100 μM) or vehicle prior to constriction with KCl (1–100 mM). Testosterone-induced vasodilatation was unaffected by endothelial denudation, flutamide treatment, AR deficiency or conjugation to BSA. Cells exposed to T-3-OCMO–BSA (10 μM) had a higher fluorescence than control cells (32.8±4.5 compared with 14.5±1.8 arbitrary units respectively; P<0.01). Incubation with testosterone (100 μM) reversibly attenuated coronary vasoconstriction to KCl (1–100 mM; 0.08±0.09 compared with 0.79±0.08 mN/mm respectively; P<0.0001). Testosterone-induced vasodilatation is independent of the vascular endothelium and nuclear AR, and is initiated at the SMC membrane, which contains testosterone binding sites. A direct calcium antagonistic action is implicated.
Skip Nav Destination
Article navigation
August 2004
-
Cover Image
Cover Image
- PDF Icon PDF LinkTable of Contents
Research Article|
July 27 2004
Testosterone-induced coronary vasodilatation occurs via a non-genomic mechanism: evidence of a direct calcium antagonism action
Richard D. JONES;
*Hormone and Vascular Biology Group, Academic Unit of Endocrinology, Division of Genomic Medicine, The University of Sheffield, Sheffield S10 2RX, U.K.
Correspondence: Dr Richard Jones (email R.D.Jones@sheffield.ac.uk).
Search for other works by this author on:
Kate M. ENGLISH;
Kate M. ENGLISH
†Department of Cardiology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Trust, Sheffield S10 2JF, U.K.
Search for other works by this author on:
T. Hugh JONES;
T. Hugh JONES
*Hormone and Vascular Biology Group, Academic Unit of Endocrinology, Division of Genomic Medicine, The University of Sheffield, Sheffield S10 2RX, U.K.
‡Centre for Diabetes and Endocrinology, Barnsley District General Hospital, Barnsley District General Hospital NHS Trust, Barnsley S75 5RT, U.K.
Search for other works by this author on:
Kevin S. CHANNER
Kevin S. CHANNER
†Department of Cardiology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Trust, Sheffield S10 2JF, U.K.
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
November 24 2003
Revision Received:
February 24 2004
Accepted:
March 01 2004
Accepted Manuscript online:
March 01 2004
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2004
Clin Sci (Lond) (2004) 107 (2): 149–158.
Article history
Received:
November 24 2003
Revision Received:
February 24 2004
Accepted:
March 01 2004
Accepted Manuscript online:
March 01 2004
Citation
Richard D. JONES, Kate M. ENGLISH, T. Hugh JONES, Kevin S. CHANNER; Testosterone-induced coronary vasodilatation occurs via a non-genomic mechanism: evidence of a direct calcium antagonism action. Clin Sci (Lond) 1 August 2004; 107 (2): 149–158. doi: https://doi.org/10.1042/CS20030386
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.