Relaxation of rabbit corpus cavernosum smooth muscle and aortic vascular endothelium induced by new nitric oxide donor substances of the nitrosyl-ruthenium complex

ABSTRACT

INTRODUCTION: Endothelial dysfunction characterized by endogenous nitric oxide (NO) deficiency made 56 percent of patients affected with erectile dysfunction decline treatment with PDE-5 inhibitors. New forms of treatment are currently being developed for this group of patients. MATERIALS AND METHODS: The study compared the effect of sodium nitroprusside (SNP) and two substances of the nitrosyl-ruthenium complex, cis-[Ru(bpy)2(SO3)(NO)]PF-6-9 ("FONO1”) and trans-[Ru(NH3)4(caffeine)(NO)]C13 ("LLNO1”) on relaxation of rabbit corpus cavernosum smooth muscle and aortic vascular endothelium. The samples were immersed in isolated baths and precontracted with 0.1 µM phenylephrine (PE) and the corresponding relaxation concentration/response curves were plotted. In order to investigate the relaxation mechanisms involved, 100 µM ODQ (a soluble guanylate cyclase-specific inhibitor), 3 µM or 10 µM oxyhemoglobin (an extracellular NO scavenger) or 1 mM L-cysteine (a nitrosyl anion-specific scavenger) was added to the samples. RESULTS: All the NO donors tested produced a significant level of relaxation in the vascular endothelium. In corpus cavernosum samples, FONO1 produced no significant effect, but LLNO1 and SNP induced dose-dependent relaxation with comparable potency (pEC50 = 6.14 ± 0.08 and 6.4 ± 0.14, respectively) and maximum effect (Emax = 82 percent vs. 100 percent, respectively). All NO donors were found to activate soluble guanylate cyclase, since the addition of the corresponding inhibitor (100 µM ODQ) completely neutralized the relaxation effect observed. The addition of oxyhemoglobin reduced the relaxation effect, but did not inhibit it completely. In aortic vascular endothelium 3 µM oxyhemoglobin decreased the relaxation effect by 26 percent on the average, while 10 µM oxyhemoglobin reduced it by over 52 percent. The addition of 100 µM L-cysteine produced no significant inhibiting effect. CONCLUSIONS: These results suggest that LLNO1...