Testosterone relaxes abdominal aorta in male Sprague-Dawley rats by opening potassium (K) channel and blockade of calcium (Ca) channel

Aim: To investigate the direct effect of testosterone and its precursor/derivative dehydroepiandrosterone (DHEA) on isolated rat abdominal aortic rings. Materials and methods: 3 mm abdominal aortic rings that were obtained from 3 months old male Sprague-Dawley rats were suspended in organ baths containing Hepes buffered PSS bubbled with 100% oxygen. Relaxation response to testosterone and DHEA was studied in noradrenalin pre-contracted rings. The role of aromatase and androgen receptor was assessed by inhibition using aminogluthetemide and blockade using flutamide respectively. Relaxation responses of the rings to testosterone in the presence of l-NAME, indomethacin, barium chloride, apamin, charybdotoxin, iberiotoxin, and nifedipine were also determined. Results: Both aromatase inhibition and androgen receptor blockade did not block the relaxing effect of testosterone on rings from rat abdominal aorta. Also there was no significant difference between testosterone relaxation response in the presence or absence of l-NAME and indomethacin. However 3 μM, BaCl₂ almost completely abolished the aortic ring relaxation response to testosterone while 1 μM, nifedipine potentiated the vasorelaxing effect of testosterone. Conclusion: Testosterone relaxes abdominal aorta directly via a non-genomic pathway which is independent of endothelial derived vasoactive substances, but involves activation of inward rectifying potassium channel (K_IR) and blockade of l-type calcium channel.