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

João Batista Gadelha De Cerqueira,Francisco Ordelei Nascimento Da Silva,Maria Elisabete Amaral De Moraes,Nilberto Robson Falcão Do Nascimento,João Victor Medeiros De Cerqueira,Ricardo Reges Maia Oliveira,Lúcio Flávio Gonzaga-Silva

doi:10.1590/s1677-55382012000500015

João Batista Gadelha De Cerqueira, Francisco Ordelei Nascimento Da Silva + Show 5 more

Open Access

https://doi.org/10.1590/s1677-55382012000500015

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Abstract

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)]C13 (Rut-Caf) and sodium nitroprusside (SNP). 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. The substances provoked significant relaxation of the cavernous smooth muscle. Both Rut-Caf and SNP determined dose-dependent relaxation with similar potency (pEC50) 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 (pEC50 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. 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.

Highlights

Human corpus cavernosum contains vascular smooth muscle, kept under tonic contraction induced by adrenergic excitation to maintain penile flaccidity [1]
Nitric oxide (NO), the endothelium-derived relaxation factor discovered by Palmer and Moncada, is the main inhibitory neuibju | Identification of mechanisms involved in the relaxation of rabbit cavernous smooth muscle rotransmitter that mediates penile erection in all animals [2]
The cyclic guanosine monophosphate (cGMP) acts in intracellular effectors, like protein kinase G (PKG), which cause diminishment of intracellular calcium and disassociation of actin and myosin fibers, leading to relaxation of the smooth muscle [2]

Summary

Introduction

Human corpus cavernosum contains vascular smooth muscle, kept under tonic contraction induced by adrenergic excitation to maintain penile flaccidity [1]. Nitric oxide (NO), the endothelium-derived relaxation factor discovered by Palmer and Moncada, is the main inhibitory neuibju | Identification of mechanisms involved in the relaxation of rabbit cavernous smooth muscle rotransmitter that mediates penile erection in all animals [2]. NO donors are substances that release NO, either in vivo or in vitro. One of these donors, sodium nitroprusside (SNP), is a powerful vasodilator utilized in patients with hypertensive crisis. Sodium nitroprusside (SNP), is a powerful vasodilator utilized in patients with hypertensive crisis It is extremely labile, induces tolerance and releases cyanide, which is toxic to the endothelium [3]

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