Title | Hydrogen sulphide is involved in testosterone vascular effect. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Bucci M, Mirone V, Di Lorenzo A, Vellecco V, Roviezzo F, Brancaleone V, Ciro I, Cirino G |
Journal | Eur Urol |
Volume | 56 |
Issue | 2 |
Pagination | 378-83 |
Date Published | 2009 Aug |
ISSN | 1873-7560 |
Keywords | Animals, Hydrogen Sulfide, In Vitro Techniques, Male, Rats, Rats, Wistar, Testosterone, Vasodilation |
Abstract | 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 H(2)S 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 degrees C and mounted to isometric force transducers. H(2)S 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 microM). Results were expressed as nmoles/mg protein. MEASUREMENTS: Vascular reactivity was evaluated by using isometric transducers. H(2)S determination was performed by using a cystathionine beta-synthetase (CBS) and cystathionine gamma 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 H(2)S. This effect was significantly reduced by PGG and BCA, two specific inhibitors of CSE. T (10 nM-10 microM) 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 H(2)S, a novel gaseous mediator. T modulates H(2)S levels by increasing the enzymatic conversion of L-cysteine to H(2)S. |
DOI | 10.1016/j.eururo.2008.05.014 |
Alternate Journal | Eur Urol |
PubMed ID | 18511180 |
Related Lab:
Related Faculty:
Annarita Di Lorenzo, Ph.D.