Characterization of relaxant mechanism of H2S in mouse corpus cavernosum

AYDINOĞLU F., ÖĞÜLENER N.

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, vol.43, no.4, pp.503-511, 2016 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 43 Issue: 4
  • Publication Date: 2016
  • Doi Number: 10.1111/1440-1681.12554
  • Journal Name: CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.503-511
  • Keywords: aminooxyacetic acid, cAMP, GMP, d, l-propargylglycine, endothelium, hydrogen sulfide, KCl channel blockers, l-cysteine, mouse corpus cavernosum, SULFIDE-INDUCED RELAXATION, GASOTRANSMITTER HYDROGEN-SULFIDE, SMOOTH-MUSCLE, NITRIC-OXIDE, POTASSIUM CHANNELS, NEUROGENIC RELAXATION, MYOCARDIAL-ISCHEMIA, REPERFUSION INJURY, ERECTILE FUNCTION, OXIDATIVE STRESS
  • Çukurova University Affiliated: Yes

Abstract

Abstract

The aim of this study was to investigate the mechanism of H2S-induced relaxation in mouse corpus cavernosal tissue. l-cysteine (10(-6)x10(-3)mol/L) and exogenous H2S (NaHS; 10(-6) to 10(-3)mol/L) induced concentration-dependent relaxation. l-cysteine-induced relaxations was reduced by d,l-propargylglycine, a cystathionine gamma lyase (CSE) inhibitor but not influenced by aminooxyacetic acid, a cystathionine beta synthase (CBS) inhibitor. l-cysteine induced relaxations, but not of those of H2S diminished in endothelium-denuded tissues. N-nitro-l-arginine (l-NA; 10(-4)mol/L), a nitric oxide synthase inhibitor, and ODQ (10(-4)mol/L), a guanylyl cyclase inhibitor, increased the H2S-induced relaxation. Zaprinast (5x10(-6)mol/L) and sildenafil (10(-6)mol/L), phosphodiesterase inhibitors, inhibited H2S-induced relaxation. Adenylyl cyclase inhibitors N-ethylmaleimide (2.5x10(-5)mol/L) and SQ22536 (10(-4)mol/L) reduced relaxation to H2S. Also, H2S-induced relaxation was reduced by KCl (50mmol/L), 4-aminopyridine (10(-3)mol/L), a K-v inhibitor, glibenclamide (10(-5)mol/L), a K-ATP inhibitor or barium chloride (10(-5)mol/L), a K-IR inhibitor. However, H2S-induced relaxation was not influenced by apamin (10(-6)mol/L), a SKCa2+ inhibitor, charybdotoxin (10(-7)mol/L), an IKCa2+ and BKCa2+ inhibitor or combination of apamin and charybdotoxin. Nifedipine (10(-6)mol/L), an L-type calcium channel blocker and atropine (10(-6)mol/L), a muscarinic receptor blocker, inhibited H2S-induced relaxation. However, H2S-induced relaxation was not influenced by ouabain (10(-4)mol/L), a Na+/K+-ATPase inhibitor. This study suggests that H2S endogenously synthesizes from l-cysteine by CSE endothelium-dependent in mouse corpus cavernosum tissue, and exogenous H2S may cause endothelium-independent relaxations via activation of K channels (K-ATP channel, K-V channels, K-IR channels), L-type voltage-gated Ca2+ channels, adenylyl cyclase/cAMP pathway and muscarinic receptor, and there is the interaction between H2S and NO/cGMP.

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