Cleber E Teixeira

Georgia Health Sciences University, Augusta, Georgia, United States

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Publications (52)153.34 Total impact

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    ABSTRACT: We tested the hypothesis that the basal release of nitric oxide (NO) from endothelial cells modulates contractile activity in the corpus cavernosum (CC) via inhibition of the RhoA/Rho-kinase signaling pathway. Cavernosal strips from wild-type (WT), endothelial nitric-oxide synthase knockout [eNOS(-/-)], and neuronal nitric-oxide synthase knockout [nNOS(-/-)] mice were mounted in myographs, and isometric force was recorded. mRNA and protein expression of key molecules in the RhoA/Rho-kinase pathway were analyzed by real-time polymerase chain reaction and Western blot, respectively. The cGMP levels were determined. The Rho-kinase inhibitors (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide (Y-27632) and (S)-(+)-2-methyl-1-[(4-methyl-5-isoquinolinyl)sulfonyl] homopiperazine (H-1152) reduced cavernosal contractions evoked by phenylephrine or electrical field stimulation (EFS) in a concentration-dependent manner, although this inhibition was less effective in tissues from eNOS(-/-) mice. Y-27632 enhanced relaxations induced by sodium nitroprusside, EFS, and NO (administered as acidified NaNO2) without affecting the cGMP content of the cavernosal strips. This enhancement was less prominent in CC from eNOS(-/-). The protein expression of RhoA, Rho-guanine dissociation inhibitor, and Rho-kinase beta did not differ among the strains. However, in eNOS(-/-) CC, the protein expression of Rho-kinase alpha and both mRNA and protein expression of p115-Rho-associated guanine exchange factor (RhoGEF), PDZ-RhoGEF, and leukemia-associated RhoGEF were up-regulated. Phosphorylation of MYPT1 at Thr696 was higher in tissues from eNOS(-/-) mice. A high concentration of Y-27632 significantly enhanced NO release in CC stimulated by EFS. These results suggest a basal release of NO from endothelial cells, which inhibits contractions mediated by the RhoA/Rho-kinase pathway and modulates the expression of proteins related to this pathway in mouse CC. It indicates that endothelial integrity is essential to the maintenance of erectile function.
    Journal of Pharmacology and Experimental Therapeutics 04/2010; 333(1):184-92. · 3.89 Impact Factor
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    ABSTRACT: To compare the direct relaxant activity of sildenafil, vardenafil, and tadalafil in the human corpus cavernosum (HCC) and to investigate their modulatory effects on nitric oxide (NO)-mediated responses. Phosphodiesterase (PDE)-5 inhibitors cause cavernosal smooth muscle relaxation and penile erection. HCC strips were mounted in 10-mL organ baths containing Krebs solution and connected to force-displacement transducers. The changes in isometric force were recorded using the Powerlab 400 data acquisition system. Corporeal smooth muscle was precontracted submaximally with phenylephrine (10 micromol/L). All PDE-5 inhibitors tested (0.001-10 micromol/L) relaxed phenylephrine-precontracted HCC with similar values of potency in a concentration-dependent manner. However, the maximal relaxations induced by tadalafil (83% +/- 4%) were significantly lower compared with sildenafil (107% +/- 5%) and vardenafil (111% +/- 3%). The NO synthesis inhibitor N-nitro-l-arginine methyl ester (100 micromol/L) caused significant rightward shifts in the concentration-response curves for sildenafil (4.0-fold), vardenafil (4.6-fold), and tadalafil (3.2-fold) in HCC tissue. The guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 micromol/L) also produced similar rightward shifts for these PDE-5 inhibitors. The cavernosal relaxations evoked by either acetylcholine or the NO donor glyceryl trinitrate were markedly potentiated by sildenafil, vardenafil, and tadalafil (0.1 micromol/L each). All PDE-5 inhibitors significantly increased the duration of electrical field stimulation-induced relaxations (8 Hz). Our findings have shown that sildenafil, vardenafil, and tadalafil relax HCC tissues in a concentration-dependent manner, but the maximal relaxation obtained with tadalafil was significantly lower than that obtained with sildenafil and vardenafil. Moreover, the PDE-5 inhibitors interacted with endogenous and exogenous NO, amplifying its HCC relaxation.
    Urology 05/2009; 74(1):216-21. · 2.42 Impact Factor
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    ABSTRACT: BAY 41-2272 (5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-pyrimidin-4-ylamine) relaxes mesenteric arteries (MA) in a synergistic fashion with nitric oxide (NO). We hypothesized that the relaxation to BAY 41-2272 is decreased in spontaneously hypertensive rats (SHR) because of the reduced NO bioavailability in this strain and that relaxation would be improved by inhibiting the oxidative stress. We aimed to evaluate the influence of oxidative stress in BAY 41-2272-induced vasorelaxation in isolated MA from SHR. MA function was evaluated by concentration-response curves to BAY 41-2272. We measured protein expression of endothelial NO synthase (eNOS), soluble guanylyl cyclase (sGC) and human-antigen R (HuR) (sGC mRNA-stabilizing protein), sGC activity and plasma levels of superoxide dismutase (SOD), and total antioxidant status (TAS). Cyclic guanosine monophosphate (cGMP)-dependent and -independent relaxation induced by BAY 41-2272 (0.0001-1 micromol/l) was impaired in SHR compared with Wistar-Kyoto (WKY). We observed reduced expression of eNOS, sGC and HuR, and decreased sGC activity in SHR. Plasma levels of SOD and TAS were also diminished in SHR. Incubation with SOD or indomethacin increased relaxation to BAY 41-2272 in SHR. Furthermore, acetylcholine (ACh)-induced relaxation was increased in the presence of BAY 41-2272 or SOD, apocynin, or indomethacin. Augmented oxidative stress in SHR impaired cGMP-dependent and -independent relaxation induced by BAY 41-2272, by decreasing NO bioavailability and sGC expression and by increasing contractile activity. Inhibiton of oxidative stress improved the relaxation of BAY 41-2272 in SHR. BAY 41-2272 might be an alternative therapeutic tool for hypertension if administrated with antioxidant compounds.
    American Journal of Hypertension 03/2009; 22(5):493-9. · 3.67 Impact Factor
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    ABSTRACT: 1. The anococcygeus muscle is part of the erectile machinery in male rodents. Phosphodiesterase (PDE) 5 inhibitors enhance and prolong the effects of cGMP, which has a key role in penile erection. The aim of the present study was to provide a functional and biochemical comparison of the three PDE5 inhibitors, namely sildenafil, tadalafil and vardenafil, in the rat anococcygeus muscle. 2. Muscle strips were mounted in 4 mL organ baths and isometric force recorded. Levels of cGMP were measured using an enzyme immunoassay kit. Western blots were used to determine PDE5 protein expression. 3. The PDE5 inhibitors concentration-dependently relaxed carbachol-precontracted anococcygeus muscle; however, vardenafil was more potent (pEC(50) = 8.11 +/- 0.05) than sildenafil (7.72 +/- 0.06) or tadalafil (7.69 +/- 0.05). Addition of N(G)-nitro-l-arginine methyl ester (100 micromol/L) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 micromol/L) to the organ baths caused significant rightward shifts in concentration-response curves for all PDE5 inhibitors. 4. Sildenafil, tadalafil and vardenafil (all at 0.1 micromol/L) caused leftward shifts in the glyceryl trinitrate (GTN) concentration-response curves (by 4.0-, 3.7- and 5.5-fold, respectively). In addition, all three PDE5 inhibitors significantly potentiated relaxation responses to both GTN (0.01-10 micromol/L) and electrical field stimulation (EFS; 1-32 Hz), with vardenafil having more pronounced effects. 5. All three PDE5 inhibitors reduced EFS-evoked contractions in a concentration-dependent manner over the concentration range 0.001-1 micromol/L. There were no significant differences between the effects of the three PDE5 inhibitors. 6. Vardenafil (0.01-0.1 micromol/L) was more potent in preventing cGMP degradation in vitro than sildenafil (0.01-0.1 micromol/L) and tadalafil (0.01-0.1 micromol/L). 7. Under control conditions, the expression of PDE5 was higher in the anococcygeus muscle than in the corpus cavernosum. 8. In conclusion, PDE5 inhibitors enhance exogenous and endogenous nitric oxide-mediated relaxation in the rat anococcygeus muscle. The potency of vardenafil was greater than that of either sildenafil or tadalafil.
    Clinical and Experimental Pharmacology and Physiology 11/2008; 36(4):358-66. · 2.16 Impact Factor
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    ABSTRACT: Phosphodiesterase type-5 (PDE5) inhibitors constitute a novel and important therapeutic option for the treatment of pulmonary hypertension. The effects of the PDE5 inhibitors sildenafil, tadalafil and vardenafil on rabbit isolated pulmonary artery ring preparations and on intracellular Ca2+ concentration of thrombin-stimulated human platelets were investigated. Rabbit pulmonary artery rings were mounted in 10 mL organ bath containing Krebs solution. Tissues were connected to force-displacement transducers, and changes in isometric force were recorded. Ca2+ flux in human washed platelets was measured. Sildenafil, tadalafil and vardenafil (0.0001-10 microM) concentration-dependently relaxed endothelium-intact and endothelium-denuded pulmonary artery rings. Endothelium denudation caused rightward shifts in the concentration-response curves to sildenafil, tadalafil and vardenafil (9-, 12- and 123-fold, respectively). Incubation with N(omega)-nitro-L-arginine methyl ester (100 microM) or ODQ (1H-[1,2,4] oxadiazolo [4,3,-a]quinoxalin-1-one) (10 microM) caused similar reductions of PDE5-induced vasorelaxations in intact rings. Sildenafil and tadalafil did not affect the phenylephrine-induced contractions, whereas vardenafil reduced the maximal responses, and shifted the phenylephrine-induced contraction curves to the right in endothelium-denuded rings (5- and 19-fold for 1 and 10 microM, respectively). Vardenafil (but neither sildenafil nor tadalafil) caused a marked rightward shift and a decrease of maximal contractile response to CaCl2. Vardenafil, but neither sildenafil nor tadalafil, significantly reduced the Ca2+ mobilization and Ca2+ influx in thrombin-stimulated washed platelets. Our results indicate that vardenafil, in contrast to sildenafil or tadalafil, also blocked Ca2+ fluxes, thus enhancing its vasorelaxation of the pulmonary artery.
    British Journal of Pharmacology 07/2008; 154(4):787-96. · 5.07 Impact Factor
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    ABSTRACT: Nitrergic nerves and endothelial cells release nitric oxide (NO) in the corpus cavernosum, a key mediator that stimulates soluble guanylyl cyclase to increase cGMP levels causing penile erection. Phosphodiesterase 5 (PDE5) inhibitors, such as sildenafil, prolong the NO effects by inhibiting cGMP breakdown. Here, we report a novel PDE5 inhibitor, lodenafil carbonate, (Bis-(2-{4-[4-ethoxy-3-(1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-benzenesulfonyl]piperazin-1-yl}-ethyl)carbonate) that is a dimer of lodenafil. We therefore aimed to compare the effects of sildenafil, lodenafil and lodenafil carbonate on in vitro human and rabbit cavernosal relaxations, activity of crude PDE extracts from human platelets, as well as stability and metabolic studies in rat, dog and human plasma. Pharmacokinetic evaluations after intravenous and oral administration were performed in male beagles. Functional experiments were conducted using organ bath techniques. Pharmacokinetics was studied in beagles by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), following oral or intravascular administration. All PDE5 inhibitors tested concentration-dependently relaxed (0.001-100 microM) phenylephrine-precontracted rabbit and human corpus cavernosum. The cavernosal relaxations evoked by either acetylcholine (0.01-100 microM) or electrical field stimulation (EFS, 1-20 Hz) were markedly potentiated by sildenafil, lodenafil and lodenafil carbonate. Lodenafil carbonate was more potent to inhibit the cGMP hydrolysis in PDE extracts compared with lodenafil and sildenafil. Following intravascular and single oral administration of lodenafil carbonate, only lodenafil and norlodenafil were detected in vivo. These results indicate that lodenafil carbonate works as a prodrug, being lodenafil the active moiety of lodenafil carbonate.
    European Journal of Pharmacology 07/2008; 591(1-3):189-95. · 2.59 Impact Factor
  • Liming Jin, Cleber E Teixeira, R Clinton Webb, Romulo Leite
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    ABSTRACT: Protein kinase C (PKC) is involved in the regulation of vascular smooth muscle contraction. However, the role of PKC in erectile function is poorly understood. This study investigated whether PKC mediates agonist-induced contractions in mouse penile tissue (corpora cavernosa). We also compared the effects of PKC activators and inhibitors on contractile responses in mouse corpus cavernosum with those in mouse aorta. Aortic rings and corpus cavernosal strips from C57BL/6J mice were mounted in the organ bath for isometric tension recording. Our data showed that a PKC(alpha/beta) selective inhibitor, G(ö)6976 (10 microM), inhibited phenylephrine and 9,11-dideoxy-11alpha,9alpha-epoxymethanoprostaglandin F(2alpha) (U46619, a thromboxane mimetic)-induced contractions in mouse aorta, reducing the maximum contraction by 94% and 17%, respectively. A non-selective PKC inhibitor, chelerythrine (30 microM), also significantly reduced phenylephrine- and U46619-induced maximum contractions in mouse aorta. However, G(ö)6976 and chelerythrine had no significant effects on phenylephrine- and U46619-induced contractions in corpus cavernosum. Furthermore, a PKC activator, phorbol-12,13-dibutyrate (0.1 microM), significantly increased contractions in aorta (208+/-14% of KCl-induced maximum contraction) but failed to cause contractions in corpus cavernosum at 1 and 10 microM. Western blot analysis data suggested that protein expression of PKC was similar in aorta and corpus cavernosum. Taken together, our data indicate that PKC does not have a significant role in agonist-induced contractions in mouse corpus cavernosum, whereas it mediates the contractile response to agonists in the aorta.
    European Journal of Pharmacology 07/2008; 590(1-3):363-8. · 2.59 Impact Factor
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    ABSTRACT: The 5-[2-ethoxy-5-(4-methylpiperazin-1-ylsulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7 H-pyrazolo[4,3-d]pyrimidin-7-one, sildenafil, is a cGMP-specific phosphodiesterase-5 (PDE5) inhibitor used for penile erectile dysfunction. In the search for more potent and selective PDE5 inhibitors, new sildenafil analogues (6a-v), characterized by the presence on the sulfonyl group in the 5' position of novel N-4-substituted piperazines or ethylenediamine moiety, were prepared by traditional and microwave-assisted synthesis and tested in rabbit isolated aorta and corpus cavernosum. Similarly to sildenafil, several analogues showed IC50 values in the nanomolar range. In the in vitro studies, all the tested compounds caused concentration-dependent relaxations in both rabbit isolated aorta and corpus cavernosum. All sildenafil analogues potentiated the nitric oxide-dependent vasodilation in endothelium-intact rabbit aorta. Compound 6f exhibited great pEC50 value in corpus cavernosum, and compounds 6r and 6u in isolated aorta were found as potent as sildenafil for inhibiting PDE5. Because several analogues were significantly more lipophilic than sildenafil, these compounds may offer a new lead for development of new sildenafil analogues.
    Journal of Medicinal Chemistry 06/2008; 51(9):2807-15. · 5.61 Impact Factor
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    ABSTRACT: To study the direct relaxant activity of 5-cyclopropyl-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-4-ylamine (BAY 41-2272) in the rabbit penile urethra and to investigate its modulatory effect on nitric oxide (NO)-mediated responses. Urothelium-intact (U+) and denuded (U-) rings were mounted in 10-mL organ baths for isometric force recording. Intracellular cyclic guanosine monophosphate (cGMP) levels were quantified with specific kits. BAY 41-2272 (0.0001 to 10 micromol/L) caused relaxation of urethral rings contracted with phenylephrine (10 micromol/L), with higher potency (P <0.01) in U+ (pEC(50) 7.77 +/- 0.09) compared with U- (pEC(50) 6.84 +/- 0.19) preparations. The NO synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (100 micromol/L) or the soluble guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3,-a]quinoxalin-1-one (ODQ) (10 micromol/L) had no effect on BAY 41-2272 responses in U+ or U- rings. The phosphodiesterase-5 inhibitor vardenafil (0.1 micromol/L) potentiated the relaxant effects of BAY 41-2272 in both U+ (10-fold) and U- (sevenfold) tissues. Ca(2+)-induced contractions in K(+) depolarized rings were significantly attenuated by BAY 41-2272 (1 micromol/L) in an ODQ-insensitive manner. BAY 41-2272 (0.03-0.3 micromol/L) increased the amplitude and duration of electrical field stimulation-induced relaxations (1 to 32 Hz), as well as those evoked by the NO donor glyceryl trinitrate (0.0001 to 10 micromol/L). BAY 41-2272 induced ODQ-resistant increases in cGMP levels above baseline (approximately twofold) in both U+ and U- rings. BAY 41-2272 relaxes penile urethra in a synergic fashion with NO. Targeting soluble guanylate cyclase with BAY 41-2272 may represent a new therapy in the management of voiding disturbances associated with impaired NO-cGMP signaling.
    Urology 03/2008; 72(3):711-5. · 2.42 Impact Factor
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    ABSTRACT: Long-term propranolol treatment reduces arterial blood pressure in hypertensive individuals mainly by reducing peripheral vascular resistance, but mechanisms underlying their vasodilatory effect remain poorly investigated. This study aimed to investigate whether long-term propranolol administration ameliorates the impairment of relaxing responses of aorta and mesenteric artery from rats made hypertensive by chronic nitric oxide (NO) deficiency, and underlying mechanisms mediating this phenomenon. Male Wistar rats were treated with N(omega)-Nitro-L-arginine methyl ester (L-NAME; 20 mg/rat/day) for four weeks. DL-Propranolol (30 mg/rat/day) was given concomitantly to L-NAME in the drinking water. Treatment with L-NAME markedly increased blood pressure, an effect largely attenuated by DL-propranolol. In phenylephrine-precontracted aortic rings, the reduction of relaxing responses for acetylcholine (0.001-10 microM) in L-NAME group was not modified by DL-propranolol, whereas in mesenteric rings the impairment of acetylcholine-induced relaxation by L-NAME was significantly attenuated by DL-propranolol. In mesenteric rings precontracted with KCl (80 mM), DL-propranolol failed to attenuate the impairment of acetylcholine-induced relaxation by L-NAME. The contractile responses to extracellular CaCl2 (1-10 mM) were increased in L-NAME group, and co-treatment with DL-propranolol reduced this response in both preparations in most Ca2+ concentrations used. The NO2/NO3 plasma levels and superoxide dismutase (SOD) activity were reduced in L-NAME-treated rats, both of which were significantly prevented by DL-propranolol. In conclusion, propranolol-induced amplification of the relaxation to acetylcholine in mesenteric arteries from L-NAME-treated rats is sensitive to depolarization. Additional mechanisms involving blockade of Ca2+ entry in the vascular smooth muscle and increase in NO bioavailability contributes to beneficial effects of long-term propranolol treatment.
    European Journal of Pharmacology 11/2007; 571(2-3):189-96. · 2.59 Impact Factor
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    ABSTRACT: We aimed to characterize the relaxation induced by the soluble guanylyl cyclase (sGC) stimulator 5-cyclopropyl-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]pyrimidin-4-ylamine (BAY 41-2272) and its pharmacological interactions with nitric oxide (NO) in the corpus cavernosum (CC) from wild-type (WT), endothelial nitric-oxide synthase (eNOS)(-/-), and neuronal (n)NOS(-/-) mice. The effect of BAY 41-2272 on superoxide formation and NADPH oxidase expression was also investigated. Tissues were mounted in myographs for isometric force recording. Enzyme immunoassay kits were used for cGMP determination. sGC activity was determined in the supernatant fractions of the cavernosal samples by the conversion of GTP to cGMP. Superoxide formation and expression of NADPH oxidase subunits were studied using the reduction of ferricytochrome c and Western blot analysis, respectively. BAY 41-2272 (0.01-10 microM) relaxed CC with pEC(50) values of 6.36 +/- 0.07 (WT), 6.27 +/- 0.06 (nNOS(-/-)), and 5.88 +/- 0.07 (eNOS(-/-)). The relaxations were accompanied by increases in cGMP levels. N(omega)-Nitro-L-arginine methyl ester inhibited BAY 41-2272-evoked responses in CC from WT and nNOS(-/-), but not eNOS(-/-).1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one reduced and sildenafil potentiated the relaxations induced by BAY 41-2272 in all groups. BAY 41-2272 enhanced NO (endogenous and exogenous)-induced relaxations in a concentration-dependent manner. Expression and activity of sGC was similar among the different groups. Superoxide formation was reduced by BAY 41-2272 (0.1-1 microM). The compound also inhibited p22(phox) and gp91(phox) expression induced by 9,11-dideoxy-11 alpha,9 alpha-epoxymethanoprostaglandin F(2 alpha (U46619). Our results demonstrated that sGC activation in the penis by BAY 41-2272 directly or via enhancement of NO effects may provide a novel treatment for erectile dysfunction, particularly in the event of an increased intrapenile oxidative stress.
    Journal of Pharmacology and Experimental Therapeutics 10/2007; 322(3):1093-102. · 3.89 Impact Factor
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    ABSTRACT: We aimed to compare the expression and function of molecular components of the RhoA/Rho-kinase signaling pathway in the contractile responses of detrusor, trigonal and urethral smooth muscle, using selective Rho-kinase inhibitors. Contractility studies and molecular approaches were employed to demonstrate the expression patterns and functional activity of the RhoA/Rho-kinase signaling pathway in the lower urinary tract. Frequency-response curves (1-32 Hz) and concentration-response curves (CRC) to carbachol (CCh, 0.01-30 microM), phenylephrine (PE, 0.01-300 microM) and endothelin-1 (ET-1, 0.01-100 nM) were significantly attenuated (p<0.01) following incubation with the Rho-kinase inhibitors H-1152 (0.1-1 microM), Y-27632 (1-10 microM) or HA-1077 (10 microM). Addition of Rho-kinase inhibitors also markedly reduced (p<0.01) the contractions evoked by either KCl (80 mM) or alpha,beta-methylene ATP (alpha,beta-mATP, 10 microM). Among the Rho-kinase inhibitors tested, H-1152 was approximately 9-16 times more potent than Y-27632 or HA-1077. In addition, basal tone of detrusor and trigonal strips was reduced following addition of Y-27632 (10 microM), H-1152 (1 microM) and HA-1077 (10 microM). The expression of RhoA, RhoGDI, leukemia-associated RhoGEF (LARG) and p115RhoGEF was similar among the detrusor, trigone and urethra, whereas Rho-kinase alpha, Rho-kinase beta and PDZ-RhoGEF protein levels were significantly lower in the urethra. Components of the RhoA/Rho-kinase signaling are expressed in detrusor, trigonal and urethral smooth muscle and dynamically regulate contraction and tone. Manipulation of RhoGEF expression may provide further understanding of mechanisms involving Ca(2+) sensitization in the lower urinary tract.
    Biochemical Pharmacology 08/2007; 74(4):647-58. · 4.58 Impact Factor
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    ABSTRACT: Penile erection involves a complex interaction between the central nervous system and local factors. It is a neurovascular event modulated by psychological and hormonal factors. The discovery of nitric oxide (NO) as an intercellular messenger or neurotransmitter paved the way for identifying important mechanisms underlying physiological and pathophysiological events in the penis, in addition to providing the knowledge for the development of new therapeutics based on a novel concept of molecule and cell interaction. Despite the fact that sinusoidal endothelial cells also produce and release NO in response to chemical and possibly physical stimuli, roles of neurogenic NO in penile erection appear to be more attractive and convincing, since the pharmacological neuromodulation represents an essential step to attaining penile erection. Erectile dysfunction (ED) is caused by a variety of pathogenic factors, particularly impaired formation and action of NO. Hence, a thorough knowledge of the physiology of erection is essential for future pharmacological innovations in the field of male ED, particularly targeting NO or intracellular cyclic GMP, which represent the most promising therapeutic approach to treat patients with ED.
    Acta Pharmacologica Sinica 07/2007; 28(6):751-5. · 2.35 Impact Factor
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    Cleber Teixeira, Fernanda Priviero, Webb R Clinton
    BMC Pharmacology 01/2007;
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    BMC Pharmacology 01/2007;
  • C. E. Teixeira, F. B. M. Priviero, R. C. Webb
    Urology 01/2007; 70(3):17-17. · 2.42 Impact Factor
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    BMC Pharmacology 01/2007;
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    ABSTRACT: The aim of this work was to evaluate the influence of run training on the responsiveness of corpus cavernosum (CC) from rats made hypertensive by treatment with nitric oxide (NO) synthesis inhibitor. Wistar rats were divided into sedentary control (C-SD), exercise training (C-TR), N(omega)-nitro-L-arginine methyl ester (L-NAME) sedentary (LN-SD) and L-NAME trained (LN-TR) groups. The run training program consisted in 8 weeks in a treadmill, 5 days/week, each session lasted 60 min. L-NAME treatment (2 and 10 mg/rat/day) started after 4 weeks of prior physical conditioning and lasted 4 weeks. Concentration-response curves were obtained for acetylcholine (ACh), sodium nitroprusside (SNP), sildenafil and BAY 41-2272. The effect of electrical field stimulation (EFS) on the relaxations responses of CC was evaluated. Run training prevented the arterial hypertension induced by L-NAME treatment (LN-SD: 135+/-2 and 141+/-2 mm Hg for both doses of L-NAME) compared to LN-SD groups (154+/-1 and 175+/-2 mm Hg, for 2 and 10 mg of L-NAME, respectively). Run training produced an increase in the maximal responses (E(max)) of CC for ACh (C-SD: 47+/-3; C-TR: 52+/-1; and LN-TR: 53+/-3%) and SNP (C-SD: 89+/-1; C-TR: 98+/-1; and LN-TR: 95+/-1%). Both potency and E(max) for ACh were reduced in a dose of 10 mg of L-NAME, and run training restored the reduction of E(max) for ACh. No changes were found for BAY 41-2271 and sildenafil. Relaxing responses to EFS was reduced by L-NAME treatment that was restored by prior physical conditioning. In conclusion, our study shows a beneficial effect of prior physical conditioning on the impaired CC relaxing responses in rats made hypertensive by chronic NO blockade.
    International Journal of Impotence Research 01/2007; 19(2):189-95. · 1.51 Impact Factor
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    BMC Pharmacology 01/2007;
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    BMC Pharmacology 01/2007;

Publication Stats

542 Citations
153.34 Total Impact Points

Institutions

  • 2005–2010
    • Georgia Health Sciences University
      • Department of Physiology
      Augusta, Georgia, United States
  • 1998–2009
    • University of Campinas
      • Faculdade de Ciências Médicas (FCM)
      Campinas, Estado de Sao Paulo, Brazil
  • 2007–2008
    • Medical College of Georgia
      Augusta, Georgia, United States
  • 2004
    • São Paulo State University
      • Departamento de Farmacologia
      São Paulo, Estado de Sao Paulo, Brazil