Artículos de revistas
Bay 41-2272, A Soluble Guanylate Cyclase Stimulator, Relaxes Isolated Human Ureter In A Standardized In Vitro Model
Urology. , v. 83, n. 1, p. 256.e1 - 256.e7, 2014.
De Nucci G.
Levi D'Ancona C.A.
Objective To characterize the relaxation induced by BAY 41-2272 in human ureteral segments. Materials and Methods Ureter specimens (n = 17) from multiple organ human deceased donors (mean age 40 ± 3.2 years, male/female ratio 2:1) were used to characterize the relaxing response of BAY 41-2272. Immunohistochemical analysis for endothelial and neuronal nitric oxide synthase, guanylate cyclase stimulator (sGC) and type 5 phosphodiesterase was also performed. The potency values were determined as the negative log of the molar to produce 50% of the maximal relaxation in potassium chloride-precontracted specimens. The unpaired Student t test was used for the comparisons. Results Immunohistochemistry revealed the presence of endothelial nitric oxide synthase in vessel endothelia and neuronal nitric oxide synthase in urothelium and nerve structures. sGC was expressed in the smooth muscle and urothelium layer, and type 5 phosphodiesterase was present in the smooth muscle only. BAY 41-2272 (0.001-100 μM) relaxed the isolated ureter in a concentration dependent manner, with a potency and maximal relaxation value of 5.82 ± 0.14 and 84% ± 5%, respectively. The addition of nitric oxide synthase and sGC inhibitors reduced the maximal relaxation values by 21% and 45%, respectively. However, the presence of sildenafil (100 nM) significantly potentiated (6.47 ± 0.10, P <.05) this response. Neither glibenclamide or tetraethylammonium nor ureteral urothelium removal influenced the relaxation response by BAY 41-2272. Conclusion BAY 41-2272 relaxes the human isolated ureter in a concentration-dependent manner, mainly by activating the sGC enzyme in smooth muscle cells rather than in the urothelium, although a cyclic guanosine monophosphate-independent mechanism might have a role. The potassium channels do not seem to be involved.831256.e1256.e7Lang, R.J., Exintaris, B., Teele, M.E., Electrical basis of peristalsis in the mammalian upper urinary tract (1998) Clin Exp Pharmacol Physiol, 25, pp. 310-321Santicioli, P., Maggi, C.A., Myogenic and neurogenic factors in the control of pyeloureteral motility and ureteral peristalsis (1998) Pharmacol Rev, 50, pp. 683-722Bozler, E., The activity of the pacemaker previous to the discharge of a muscular impulse (1942) Am J Physiol, 136, pp. 543-552Woodburne, R.T., Lapides, J., The ureteral lumen during peristalsis (1972) Am J Anat, 133, pp. 255-258Moe, O.W., Kidney stones: Pathophysiology and medical management (2006) Lancet, 367, pp. 333-344Lotan, Y., Pearle, M., Cost-effectiveness of primary prevention strategies for nephrolithiasis (2011) J Urol, 186, pp. 550-555Simon, J., Roumeguere, T., Vaessen, C., Conservative management of ureteric stones (1997) Acta Urol Belg, 65, pp. 7-9Seitz, M., Liatsikos, E., Porpiglia, F., Medical therapy to facilitate the passage of stones: What is the evidence? (2009) Eur Urol, 56, pp. 455-471Delabella, M., Milanese, G., Muzzonigro, G., Efficacy of tamsulosin in the medical management of juxtavesical ureteral stones (2003) J Urol, 170, pp. 2202-2205Michel, M.C., De La Rosette, J.J., Alpha-blocker treatment of urolithiasis (2006) Eur Urol, 50, pp. 213-214Pedro, R.N., Hinck, B., Hendlin, K., Alfuzosin stone expulsion therapy for distal ureteral calculi: A double-blind, placebo controlled study (2008) J Urol, 179, pp. 2244-2247Iselin, C.E., Ny, L., Larsson, B., The nitric oxide synthase/nitric oxide and heme oxygenase/carbon monoxide pathways in the human ureter (1998) Eur Urol, 33, pp. 214-221Ignarro, L.J., Heme-dependent activation of guanylate cyclase by nitric oxide: A novel signal transduction mechanism (1991) Blood Vessels, 28, pp. 67-73Stasch, J.-P., Becker, E.M., Alonso-Alija, C., NO-independent regulatory site on soluble guanylate cyclase (2001) Nature, 410, pp. 212-215Teixeira, C.E., Priviero, F.B., Webb, R.C., Molecular mechanisms underlying rat mesenteric artery vasorelaxation induced by the nitric oxide-independent soluble guanylyl cyclase stimulators BAY 41-2272 [5-cyclopropyl-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl] pyrimidin-4- ylamine] and YC-1 [3-(5'-hydroxymethyl- 2'-furyl)-1-benzyl Indazole] (2006) J Pharmacol Exp Ther, 317, pp. 258-266Teixeira, C.E., Priviero, F.B., Todd, Jr.J., Vasorelaxing effect of BAY 41-2272 in rat basilar artery: Involvement of cGMP-dependent and independent mechanisms (2006) Hypertension, 47, pp. 596-602Baracat, J.S., Teixeira, C.E., Okuyama, C.E., Relaxing effects induced by the soluble guanylyl cyclase stimulator BAY 41-2272 in human and rabbit corpus cavernosum (2003) Eur J Pharmacol, 477, pp. 163-169Báu, F.R., Mónica, F.Z., Priviero, F.B., Evaluation of the relaxant effect of the nitric oxide-independent soluble guanylyl cyclase stimulator BAY 41-2272 in isolated detrusor smooth muscle (2010) Eur J Pharmacol, 637, pp. 171-177Capel, R.O., Mónica, F.Z., Porto, M., Role of a novel tetrodotoxin-resistant sodium channel in the nitrergic relaxation of corpus cavernosum from the South American rattlesnake Crotalus durissus terrificus (2011) J Sex Med, 8, pp. 1616-1625Gratzke, C., Ückert, S., Kedia, G., In vitro effects of PDE5 inhibitors sildenafil, vardenafil and tadalafil on isolated human ureteral smooth muscle: A basic research approach (2007) Urol Res, 35, pp. 49-54Ferguson, D.R., Kennedy, I., Burton, T.J., ATP is released from rabbit urinary bladder epithelial cells by hydrostatic pressure changes - A possible sensory mechanism? (1997) J Physiol, 505 (PART 2), pp. 503-511Gillespie, J.I., Markerink-Van Ittersum, M., De Vente, J., Endogenous nitric oxide/cGMP signalling in the guinea pig bladder: Evidence for distinct populations of sub-urothelial interstitial cells (2006) Cell Tissue Res, 325, pp. 325-332Fathian-Sabet, B., Bloch, W., Klotz, T., Localization of constitutive nitric oxide synthase isoforms and the nitric oxide target enzyme soluble guanylyl cyclase in the human bladder (2001) J Urol, 165, pp. 1724-1729Lekontseva, O., Chakrabarti, S., Jiang, Y., Role of neuronal nitric-oxide synthase in estrogen-induced relaxation in rat resistance arteries (2011) J Pharmacol Exp Ther, 339, pp. 367-375Evgenov, O.V., Pacher, P., Schmidt, P.M., NO-independent stimulators and activators of soluble guanylate cyclase: Discovery and therapeutic potential (2006) Nat Rev Drug Discov, 5, pp. 755-768Schmidt, H.H., Schmidt, P.M., Stasch, J.P., NO- and haem-independent soluble guanylate cyclase activators (2009) Handb Exp Pharmacol, 191, pp. 309-339Roger, S., Badier-Commander, C., Paysant, J., The anti-aggregating effect of BAY 41-2272, a stimulator of soluble guanylyl cyclase, requires the presence of nitric oxide (2010) Br J Pharmacol, 161, pp. 1044-1058Bazán-Perkins, B., CGMP reduces the sarcoplasmic reticulum Ca+2 loading in airway smooth muscle cells: A putative mechanism in the regulation of Ca+2 by cGMP (2012) J Muscle Cell Res Motil, 32, pp. 375-382Nagasaki, S., Nakano, Y., Masuda, M., Phosphodiesterase type 9 (PDE9) in the human lower urinary tract: An immunohistochemical study (2012) BJU Int, 109, pp. 934-940De Moura, R.S., De Lemos Neto, M., Effects of potassium channel modulators cromakalin, tetraethylammonium and glibenclamide on the contractility of the isolated human ureter (1996) J Urol, 156, pp. 276-280