Hydrogen Sulphide Is Involved in Testosterone Vascular Effect

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• 作者：Mariarosaria Bucci ; Vincenzo Mirone ; Annarita Di Lorenzo ; Valentina Vellecco ; Fiorentina Roviezzo ; Vincenzo Brancaleone ; Imbimbo Ciro ; Giuseppe Cirino
• 关键词：Testosterone ; Hydrogen sulphide ; L-cysteine ; Propargylglycine ; β ; -cyano-L-alanine ; Cystathionine γ ; -lyase ; Vascular reactivity
• 刊名：European Urology
• 出版年：2009
• 出版时间：August 2009
• 年：2009
• 卷：56
• 期：2
• 页码：378-384
• 全文大小：579 K

文摘

Background

Testosterone (T) induces a rapid relaxation in vascular tissues of different species due to a nongenomic effect of this steroid on vessels. Different mechanisms have been proposed to explain T-induced vasodilatation but the effective mechanism(s) and the mediators involved are still a matter of debate.

Objectives

We have evaluated if H₂S pathway is involved in T vascular effects.

Design and setting

Male Wistar rats were sacrificed and thoracic aorta was rapidly dissected and cleaned from fat and connective tissue. Rings of 2–3 mm length were cut and placed in organ baths filled with oxygenated Krebs solution at 37 °C and mounted to isometric force transducers. H₂S determination was performed on thoracic aortic rings incubated with T or vehicle and in presence of inhibitors. H2S concentration was calculated against a calibration curve of NaHS (3–250 μM). Results were expressed as nmoles/mg protein.

Measurements

Vascular reactivity was evaluated by using isometric transducers. H₂S determination was performed by using a cystathionine β-synthetase (CBS) and cystathionine γ lyase (CSE) activity assay. CSE and CBS protein levels were assessed by Western blot analysis. Statistical analysis was performed by using two-way ANOVA and unpaired Student's t-test where appropriate.

Results

T significantly increased conversion of L-cysteine to H₂S. This effect was significantly reduced by PGG and BCA, two specific inhibitors of CSE. T (10 nM–10 μM) induced a concentration-dependent vasodilatation of rat aortic rings in vitro that was significantly and concentration-dependent inhibited by PGG, BCA, and glybenclamide. Incubation of aorta with T up to 1 h did not change CBS/CSE expression, suggesting that T modulates enzymatic activity.

Conclusions

Here we demonstrate that T vasodilator effect involves H₂S, a novel gaseous mediator. T modulates H₂S levels by increasing the enzymatic conversion of L-cysteine to H₂S.