Identification of mechanisms involved in the relaxation of rabbit cavernous smooth muscle by a new nitric oxide donor ruthenium compound

Abstract

ARTICLE INFO _________________________________________________________ ___________________Purpose: The aim of this study was to evaluate the relaxation in vitro of cavernous smooth muscle induced by a new NO donor of the complex nitrosil-ruthenium, named trans-[Ru(NH3) 4 (caffeine)(NO)]C 13 (Rut-Caf) and sodium nitroprusside (SNP). Materials and Methods:The tissues, immersed in isolated bath systems, were pre-contracted with phenilephrine (PE) (1 µM) and then concentration-response curves (10 -12 -10 -4 M) were obtained. To clarify the mechanism of action involved, it was added to the baths ODQ (10 µM, 30 µM), oxyhemoglobin (10 µM), L-cysteine (100 µM), hydroxicobalamine (100 µM), glibenclamide, iberotoxin and apamine. Tissue samples were frozen in liquid nitrogen to measure the amount of cGMP and cAMP produced. Results: The substances provoked significant relaxation of the cavernous smooth muscle. Both Rut-Caf and SNP determined dose-dependent relaxation with similar potency (pEC 50 ) and maximum effect (E max ). The substances showed activity through activation of the soluble guanylyl cyclase (sGC), because the relaxations were inhibited by ODQ. Oxyhemoglobin significantly diminished the relaxation effect of the substances. L--cysteine failed to modify the relaxations caused by the agents. Hydroxicobalamine significantly diminished the relaxation effect of Rut-Caf. Glibenclamide significantly increased the efficacy of Rut-Caf (pEC 50 4.09 x 7.09). There were no alterations of potency or maximum effect of the substances with the addition of the other ion channel blockers. Rut-Caf induced production of significant amounts of cGMP and cAMP during the relaxation process. Conclusions: In conclusion, Rut-Caf causes relaxation of smooth muscle of corpus cavernosum by means of activation of sGC with intracellular production of cGMP and cAMP; and also by release of NO in the intracellular environment. Rut-Caf releases the NO free radical and it does not act directly on the potassium ion channels.

Relaxation Effect of Patchouli Alcohol in Rat Corpus Cavernous and Its Underlying Mechanisms

“…PGI 2 may increase the concentration of cAMP in the corpus cavernosum smooth muscle cells by prostaglandin receptors stimulation [24,25]. e binding of cAMP to the cAMP-dependent protein kinase PKA reduces the intracellular calcium levels [26] and leads to the relaxation of the corpus cavernosum [27]. However, in the present study, the cyclooxygenase inhibitor indomethacin had no effect on the PA-induced relaxation in endothelium-intact corpus cavernosum.…”

Additive effects of Artemisia capillaris extract and scopoletin on the relaxation of penile corpus cavernosum smooth muscle

“…31 This decreased the intracellular calcium level leading to the relaxation of PCCSM. 32 This study showed that ACE or scopoletin had a significant relaxation effect in a concentration-dependent manner on PCCSM ( Figure 2). ACE or scopoletin also increased the cAMP and cGMP levels in the perfusate ( Table 2).…”

Bronchodilator Effect of Crataegus azarolus var aronia Unripped Fruit Extracts on Rat’s Tracheal Smooth Muscle

“…This indicates that the relaxant effect of NO in rat tracheal smooth muscle is due to the activation of guanylate cyclase and production of the second messenger cGMP which reduces intracellular Ca2 + in smooth muscle cells. This mechanism was confirmed by (20) , who concluded that cGMP activates intracellular effectors, such as PKG, which decreasing the intracellular Ca 2+ and dissociation of actin and myosin filaments and finally leading to SMCs relaxation.…”