Involvement of RhoA/Rho-kinase in L-cysteine/H2S pathway-induced inhibition of agonist-mediated corpus cavernosal smooth muscle contraction

WOS: 000460714100008PubMed ID: 30768962Rho-kinase activity is a key regulator in the maintenance of corporal vasoconstriction and penile detumescense. Also, importance of L-cysteine/H2S pathway in erectile tissue has been shown; however it is currently unknown the role RhoA/Rho-kinase pathway in H2S-induced inhibition in cavernosal tissue. We investigated the role of RhoA/Rho-kinase pathway in the inhibitory effect of L-cysteine and NaHS, as endogenous and exogenous H2S, respectively, on phenylephrine-induced contractions of mouse cavernosal strips. Phenylephrine, alpha(1) receptor agonist, (10 nM-100 mu M) induced a concentration-dependent contraction in CC. L-cysteine (endogenous H2S substrate; 10 mM) and exogenous H2S (NaHS; 1 mM) significantly inhibited the contractile response to phenylephrine (P < 0.05). Inhibition of CSE and CBS enzymes by PAG (10 mM) and AOAA (1 mM), respectively, significantly reversed the inhibitory effects of L-cysteine on phenylephrine-induced contraction (P < 0.05). Y-27632 (1 mu M), a specific Rho-kinase inhibitor, significantly augmented the inhibitory effect of L-cysteine and NaHS on phenylephrine-induced contraction, and this inhibition was reversed by PAG and AOAA (P < 0.05). In addition, the formation of H2S was increased by approximately 1.8 fold over basal values after incubation of tissue homogenates with L-cysteine. Y-27632 significantly increased both basal and L-cysteine-induced H2S formation and this augmentation diminished by PAG and AOAA (P < 0.05). Furthermore, the pMYPT-1 expression was significantly decreased by L-cysteine, NaHS or Y-27632 alone. Also, pMYPT-1 expression was completely abolished by the L-cysteine/NaHS plus Y-27632 combination, and this inhibition was reversed by PAG and AOAA (P < 0.05). These results suggest that there is an interaction between Rho-kinase and H2S pathways. Rho-kinase may be, at least in part, inhibits CSE/CBS enzymes in mouse corpus cavernosal tissue; however, it is not excluded the other kinases such as PKC and Zip-kinase.Cukurova University Research FoundationCukurova University [TF2013BAP2]This study was supported by Cukurova University Research Foundation (TF2013BAP2)

Effect of aerial part and root extracts from Ferulago mughlae Pesmen and Ferulago sandrasica Pesmen & Quezel growing in Turkey on erectile dysfunction in streptozotocin-induced diabetic rats

WOS: 000459615300010Ferulago species have been utilised since ancient times as antihelmentic, peptic, sedative and aphrodisiac, and as the seasoning in view of their special odors. In Turkish traditional medicine, the roots from some members of this genus are utilized as aphrodisiac, so we determined to show in vitro relaxant effect of F. mughlae Pesmen and F. sandrasica Pesmen & Quezel species extracts on corpus cavernosum (CC). A totality of 20 adult male Sprague-Dawley rats (diabetic and control groups) were induced by single intraperitoneal injection of 40 mg/kg of Streptozotocin. In vitro organ bath tests were carried out on rats to evaluate isometric pressure. Tissues were stretched with phenylephrine (Phe), and relaxation responses relevant to acetylcholine (ACh, 1 mM), sodium nitroprusside (SNP 0.1 mu M) and electrical field stimulation (EFS, frequency 20 Hz) were gained. Whole these concentration-response curves were replicated with aqueous extracts obtained from the aerial parts and roots. The extracts were active in both groups. It was found that root extracts of F. mughlae and F. sandrasica yielded 97.80% and 97.55% relaxation. Among the extracts of roots (especially roots of F. mughlae) showed the best activity. On the other hand, lyophilized aqueous extracts of aerial part (especially F. sandrasica) showed the worst activity. Based on this findings, the roots of this species deserve further in vivo assessments for their aphrodisiac potential

Evaluation of combined therapeutic effects of hydrogen sulfide donor sodium hydrogen sulfide and phosphodiesterase type-5 inhibitor tadalafil on erectile dysfunction in a partially bladder outlet obstructed rat model

Aims: To evaluate the impacts of hydrogen sulfide (H2S) donor, sodium hydrogen sulfide (NaHS), and phosphodiesterase type-5 inhibitor (PDE5i), tadalafil per se and their combination treatment on partial bladder outlet obstruction (PBOO)-induced erectile dysfunction (ED). Methods: Sprague-Dawley rats were equally divided into five groups: (a) sham-operated control; (b) PBOO; (c) PBOO-treated with NaHS (5.6 mg/kg/day, ip); (d) PBOO-treated with tadalafil (2 mg/kg/day, oral); and (e) PBOO-treated with combination of NaHS and tadalafil. The obstruction was created by urethral ligation for 6 weeks. In vivo erectile responses, in vitro relaxant and contractile responses in penile tissue as well as protein expression of nitric oxide synthases (NOS), H2S synthesis enzymes, oxidative stress, hypoxia, fibrosis markers, and the smooth muscle/collagen ratio and apoptosis were analyzed. Results: Combined treatment entirely returned increased bladder mass, reduced erectile responses, relaxation responses to acetylcholine, and electrical field stimulation in obstructed rats, while partial amelioration was observed after mono-treatment. Decreased neuronal NOS and 3-mercaptopiruvate transferase enzyme expressions in penile tissue from obstructed rats were also entirely restored by the combined treatment. Mono-treatment partially improved increased hypoxia, oxidative stress, fibrosis markers, decreased smooth muscle mass, and H2S levels, while combined therapy completely recovered. Conclusions: The combination therapy with H2S donor and PDE5i had positive effects on erectile responses through the improvement of ischemia-induced morphological and functional penile alterations in obstruction. H2S and NO may likely play a synergistic role in the regulation of erectile function and have constructive effects on clinical outcomes in male patients with ED and benign prostatic hyperplasia/lower urinary tract symptoms

The beneficial effect of clove essential oil and its major component, eugenol, on erectile function in diabetic rats.

Diabetic men are at a higher risk of erectile dysfunction (ED). A tropical plant, clove (Syn. Eugenia caryophyllata, Caryophyllus aromaticus L., Syzygium aromaticum (L.) Merr. & L.M. Perry) from the Myrtaceae family has displayed aphrodisiac activity. The present research aimed to investigate the impacts of clove essential oil (CEO) and the ingredient of CEO, eugenol (E) on ED in diabetic rats. We divided Sprague-Dawley rats into control and diabetic groups. Erectile function was evaluated before and after CEO and E intracavernosal injection. CEO- and E-induced relaxation responses were investigated in isolated corpus cavernosum (CC) using various inhibitors. The intracavernous administration of CEO and E restored erectile responses in diabetic rats. CEO and E induced remarkable relaxation in all groups. CEO- and E-induced relaxation responses were partially inhibited after pre-contraction with KCl. Tetraethylammonium and glibenclamide inhibited the relaxation response to CEO. Glibenclamide inhibited maximum relaxation to E. The inhibitors of nitric oxide synthase (NOS), soluble guanylyl cyclase and nifedipine did not change CEO- and E-induced relaxation responses. The current results suggest that CEO and the major compound of the essential oil, E improved diabetes-induced ED in rats, and CEO caused CC relaxation via K channels independently NO signalling pathway

The beneficial effect of clove essential oil and its major component, eugenol, on erectile function in diabetic rats.

Diabetic men are at a higher risk of erectile dysfunction (ED). A tropical plant, clove (Syn. Eugenia caryophyllata, Caryophyllus aromaticus L., Syzygium aromaticum (L.) Merr. & L.M. Perry) from the Myrtaceae family has displayed aphrodisiac activity. The present research aimed to investigate the impacts of clove essential oil (CEO) and the ingredient of CEO, eugenol (E) on ED in diabetic rats. We divided Sprague-Dawley rats into control and diabetic groups. Erectile function was evaluated before and after CEO and E intracavernosal injection. CEO- and E-induced relaxation responses were investigated in isolated corpus cavernosum (CC) using various inhibitors. The intracavernous administration of CEO and E restored erectile responses in diabetic rats. CEO and E induced remarkable relaxation in all groups. CEO- and E-induced relaxation responses were partially inhibited after pre-contraction with KCl. Tetraethylammonium and glibenclamide inhibited the relaxation response to CEO. Glibenclamide inhibited maximum relaxation to E. The inhibitors of nitric oxide synthase (NOS), soluble guanylyl cyclase and nifedipine did not change CEO- and E-induced relaxation responses. The current results suggest that CEO and the major compound of the essential oil, E improved diabetes-induced ED in rats, and CEO caused CC relaxation via K channels independently NO signalling pathway

The beneficial effect of clove essential oil and its major component, eugenol, on erectile function in diabetic rats

Diabetic men are at a higher risk of erectile dysfunction (ED). A tropical plant, clove (Syn. Eugenia caryophyllata, Caryophyllus aromaticus L., Syzygium aromaticum (L.) Merr. \& L.M. Perry) from the Myrtaceae family has displayed aphrodisiac activity. The present research aimed to investigate the impacts of clove essential oil (CEO) and the ingredient of CEO, eugenol (E) on ED in diabetic rats. We divided Sprague-Dawley rats into control and diabetic groups. Erectile function was evaluated before and after CEO and E intracavernosal injection. CEO- and E-induced relaxation responses were investigated in isolated corpus cavernosum (CC) using various inhibitors. The intracavernous administration of CEO and E restored erectile responses in diabetic rats. CEO and E induced remarkable relaxation in all groups. CEO- and E-induced relaxation responses were partially inhibited after pre-contraction with KCl. Tetraethylammonium and glibenclamide inhibited the relaxation response to CEO. Glibenclamide inhibited maximum relaxation to E. The inhibitors of nitric oxide synthase (NOS), soluble guanylyl cyclase and nifedipine did not change CEO- and E-induced relaxation responses. The current results suggest that CEO and the major compound of the essential oil, E improved diabetes-induced ED in rats, and CEO caused CC relaxation via K+ channels independently NO signalling pathway