Study of the rapid vasodilating effect induced by 5β-dihydrotestosterone in the isolated pulmonary arteries of female and male rats

INTRODUCTION: The vasoactive androgen 5β-dihydrotestosterone (5β-DHT), which lacks androgenic or estrogenic activity, induces potent vasorelaxation across vascular beds in several mammals, thereby eliciting hypotension. Therefore, a potential vasorelaxation may occur in the pulmonary arteries of rats, which could be relevant to pulmonary arterial hypertension. METHODOLOGY: Pulmonary arteries from female and male rats were isometrically recorded and pre-constricted with KCl. 5β-DHT and its precursor, testosterone (T), were tested separately at different concentrations. Cumulative concentration-response curves were obtained, and potency (inhibitory concentration 50) and efficacy were calculated and compared. RESULTS: The potency of T did not differ between females and males. 5β-DHT was 2.2 times more potent than T in females and 6.6 times more potent in males, with greater efficacy than T in males. The rank order of vasodilating potency was: 5β-DHT>>T in females and 5β-DHT >>>>>>>T in males. The acute vasorelaxation of 5β-DHT was operative in the pulmonary arteries of females and males; the effect had a very rapid time course and was reversible after washout. Protein synthesis or transcription inhibitors did not affect its vasodilating effect, indicating that it acts through a nongenomic mechanism in pulmonary arteries. CONCLUSION: The data showed that 5β-DHT induced stronger nongenomic vasorelaxation than its precursor in females and males, which may be due to their different structural conformations. Pulmonary arteries are a target for this 5β-reduced androgen to induce relaxation.