Biomechanical Factors Predisposing to Knee Injuries in Junior Female Basketball Players.

This cross-sectional observational study aims to determine isokinetic normality data at different speeds, and isometric data of ankle and knee joints, in healthy basketball players aged 15-16 years old. The participants were recruited through non-probabilistic convenience sampling. Sociodemographic, anthropometric, and biomechanical variables were collected. The study involved 42 participants. Right-leg dominance was higher in women (85.7%) than in men (78.6%). Men had a higher weight, height, and body mass index compared to women. Statistically significant differences were observed between sex and height (p < 0.001). Significant differences were found between sexes in knee flexor and extensor strength at different isokinetic speeds (30°, 120°, and 180°/s), except for the maximum peak strength knee flexion at 180°/s in the right leg. In the ankle, the variables inversion, eversion, and work strength values at different isokinetic speeds and full RoM, by sex, were not significantly different, except for the right (p = 0.004) and the left (p = 0.035) ankle full RoM. The study found lower knee extensor strength in women, indicating the need to improve knee flexor/extensor strength in women to match that of men, as seen in other joints. The results can guide the development of preventive and therapeutic interventions for lower limb injuries in basketball players.

Biomechanical analysis of barefoot walking and three different sports footwear in children aged between 4 and 6 years old.

The technological transformation and advertising utilized in the footwear industry significantly impact purchasing decisions. The gait properties, barefoot and with shoes, change depending on the footwear structure. The aim of this work is the biomechanical analysis of walking barefoot and with different sports shoes in a controlled group of 12 children between 4 and 6 years old. Kinematic and spatiotemporal variables were analyzed using a BTS motion capture analysis system with the Helen Hayes protocol. Previously, a survey was carried out with 262 families with children between 4 and 6 years old to justify the choice of footwear for this study. No significant differences were found between any of the measured conditions. The kinematic results showed significant differences in the ankle (right sagittal plane p = 0.04, left p < 0.01; right frontal plane p < 0.01, left p < 0.01), knee (right and left sagittal plane p < 0.01) and hip (right sagittal plane p < 0.01, left p = 0.04; right frontal plane p = 0.03). Additionally, the post hoc analysis revealed significant differences between barefoot gait and different footwear. The footwear used for this study and each one's various characteristics are not preponderant in the spatiotemporal and kinematic parameters of the children's gait. Thus, the footwear purchase may be conditioned by its design or composition and other properties may not be relevant.

Experiences and mediating factors in nurses' responses to electronic device alarms: A phenomenological study.

AIM: This study aims to explore the experiences and mediating factors of nurses' responses to electronic device alarms in critical care units (CCUs). BACKGROUND: Alarm fatigue occasionally has adverse consequences for patient safety. METHODS: This qualitative study was designed and analysed following Giorgi's descriptive phenomenological approach. Seventeen nurses were theoretically sampled, reaching information saturation. Semistructured interviews were used to collect the data. RESULTS: Three central themes explained nurses' experiences: general perceptions about alarms (basic equipment of the CCU), strategies to reduce false alarms (training in the configuration of monitors, customization of the alarms to fit he patient's condition. teamwork and taking advantage of the development of technology) and key elements of the response to alarms (information about patient's condition, nurses' clinical experience, type of CCU, 'cry-wolf' phenomenon and nurse/patient ratio). CONCLUSIONS: To reduce false alarms, nurses need further postgraduate training, training on monitors and customizing alarms to fit the patient's health status. The complex process of deciding to respond to an alarm includes environmental, professional variables and patient status. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers should ensure that nurses have sufficient experience and training in the CCU, improve the nurse/patient ratio, promote teamwork and ensure that the devices are the latest generation.

Radiation exposure awareness from patients undergoing nuclear medicine diagnostic 99mTc-MDP bone scans and 2-deoxy-2-(18F) fluoro-D-glucose PET/computed tomography scans.

INTRODUCTION: Medical imaging is on average the largest source of artificial radiation exposure worldwide. This study seeks to understand patient's awareness of radiation exposure derived from nuclear medicine diagnostic scans and assess if current information provided by leaflets is adequate. METHODS: Single-centre cross-sectional questionnaire study applied to bone scan and FDG PET/computed tomography patients, at a nuclear medicine and PET/computed tomography department over a 15-week period in 2018. Questionnaires on dose comparators were designed in collaboration with patients, public, and experts in radiation exposure. Qualitative data were analysed using thematic analysis and quantitative data using SPSS (V. 24). RESULTS: A total of 102 questionnaires were completed (bone scan = 50; FDG PET/computed tomography = 52). Across both groups, 33/102 (32.4%) patients reported having a reasonable understanding of nuclear medicine and 21/102 (20.6%) reported a reasonable knowledge of ionising radiations. When asked to compare the exposure dose of respective scans with common comparators 8/50 (16%) of bone scan patients and 11/52 (21.2%) FDG PET/computed tomography answered correctly. On leaflet information, 15/85 (17.6%) patients reported the leaflets do not provide enough information on radiation exposure and of these 10/15 (66.7%) commented the leaflets should incorporate more information on radiation exposure dose. CONCLUSION: More observational and qualitative studies in collaboration with patients are warranted to evaluate patients' understanding and preferences in communication of radiation exposure from nuclear medicine imaging. This will ensure communication tools and guidelines developed to comply with ionising radiation (medical exposure) regulation 2017 are according to patients needs and preferences.

Impaired Excitatory Neurotransmission in the Urinary Bladder from the Obese Zucker Rat: Role of Cannabinoid Receptors.

Metabolic syndrome (MS) is a known risk factor for lower urinary tract symptoms. This study investigates whether functional and expression changes of cannabinoid CB1 and CB2 receptors are involved in the bladder dysfunction in an obese rat model with insulin resistance. Bladder samples from obese Zucker rat (OZR) and their respective controls lean Zucker rat (LZR) were processed for immunohistochemistry and western blot for studying the cannabinoid receptors expression. Detrusor smooth muscle (DSM) strips from LZR and OZR were also mounted in myographs for isometric force recordings. Neuronal and smooth muscle CB1 and CB2 receptor expression and the nerve fiber density was diminished in the OZR bladder. Electrical field stimulation (EFS) and acetylcholine (ACh) induced frequency- and concentration-dependent contractions of LZR and OZR DSM. ACh contractile responses were similar in LZR and OZR. EFS-elicited contractions, however, were reduced in OZR bladder. Cannabinoid receptor agonists and antagonists failed to modify the DSM basal tension in LZR and OZR In LZR bladder, EFS responses were inhibited by ACEA and SER-601, CB1 and CB2 receptor agonists, respectively, these effects being reversed by ACEA plus the CB1 antagonist, AM-251 or SER-601 plus the CB2 antagonist, AM-630. In OZR bladder, the inhibitory action of ACEA on nerve-evoked contractions was diminished, whereas that SER-601 did not change EFS responses. These results suggest that a diminished function and expression of neuronal cannabinoid CB1 and CB2 receptors, as well as a lower nerve fiber density is involved in the impaired excitatory neurotransmission of the urinary bladder from the OZR.

Pre- and post-junctional bradykinin B2 receptors regulate smooth muscle tension to the pig intravesical ureter.

AIMS: Neuronal and non-neuronal bradykinin (BK) receptors regulate the contractility of the bladder urine outflow region. The current study investigates the role of BK receptors in the regulation of the smooth muscle contractility of the pig intravesical ureter. METHODS: Western blot and immunohistochemistry were used to show the expression of BK B1 and B2 receptors and myographs for isometric force recordings. RESULTS: B2 receptor expression was consistently detected in the intravesical ureter urothelium and smooth muscle layer, B1 expression was not detected where a strong B2 immunoreactivity was observed within nerve fibers among smooth muscle bundles. On ureteral strips basal tone, BK induced concentration-dependent contractions, were potently reduced by extracellular Ca(2+) removal and by B2 receptor and voltage-gated Ca(2+) (VOC) channel blockade. BK contraction did not change as a consequence of urothelium mechanical removal or cyclooxygenase and Rho-associated protein kinase inhibition. On 9,11-dideoxy-9a,11a-methanoepoxy prostaglandin F2α (U46619)-precontracted samples, under non-adrenergic non-cholinergic (NANC) and nitric oxide (NO)-independent NANC conditions, electrical field stimulation-elicited frequency-dependent relaxations which were reduced by B2 receptor blockade. Kallidin, a B1 receptor agonist, failed to increase preparation basal tension or to induce relaxation on U46619-induced tone. CONCLUSIONS: The present results suggest that BK produces contraction of pig intravesical ureter via smooth muscle B2 receptors coupled to extracellular Ca(2+) entry mainly via VOC (L-type) channels. Facilitatory neuronal B2 receptors modulating NO-dependent or independent NANC inhibitory neurotransmission are also demonstrated.

Hydrogen sulfide plays a key role in the inhibitory neurotransmission to the pig intravesical ureter.

According to previous observations nitric oxide (NO), as well as an unknown nature mediator are involved in the inhibitory neurotransmission to the intravesical ureter. This study investigates the hydrogen sulfide (H2S) role in the neurogenic relaxation of the pig intravesical ureter. We have performed western blot and immunohistochemistry to study the expression of the H2S synthesis enzymes cystathionine γ-lyase (CSE) and cystathionine ß-synthase (CBS), measurement of enzymatic production of H2S and myographic studies for isometric force recording. Immunohistochemical assays showed a high CSE expression in the intravesical ureter muscular layer, as well as a strong CSE-immunoreactivity within nerve fibres distributed along smooth muscle bundles. CBS expression, however, was not consistently observed. On ureteral strips precontracted with thromboxane A2 analogue U46619, electrical field stimulation (EFS) and the H2S donor P-(4-methoxyphenyl)-P-4-morpholinylphosphinodithioic acid (GYY4137) evoked frequency- and concentration-dependent relaxations. CSE inhibition with DL-propargylglycine (PPG) reduced EFS-elicited responses and a combined blockade of both CSE and NO synthase (NOS) with, respectively, PPG and NG-nitro-L-arginine (L-NOARG), greatly reduced such relaxations. Endogenous H2S production rate was reduced by PPG, rescued by addition of GYY4137 and was not changed by L-NOARG. EFS and GYY4137 relaxations were also reduced by capsaicin-sensitive primary afferents (CSPA) desensitization with capsaicin and blockade of ATP-dependent K+ (KATP) channels, transient receptor potential A1 (TRPA1), transient receptor potential vanilloid 1 (TRPV1), vasoactive intestinal peptide/pituitary adenylyl cyclase-activating polypeptide (VIP/PACAP) and calcitonin gene-related peptide (CGRP) receptors with glibenclamide, HC030031, AMG9810, PACAP6-38 and CGRP8-37, respectively. These results suggest that H2S, synthesized by CSE, is involved in the inhibitory neurotransmission to the pig intravesical ureter, through an NO-independent pathway, producing smooth muscle relaxation via KATP channel activation. H2S also promotes the release of inhibitory neuropeptides, as PACAP 38 and/or CGRP from CSPA through TRPA1, TRPV1 and related ion channel activation.

Powerful relaxation of phosphodiesterase type 4 inhibitor rolipram in the pig and human bladder neck.

INTRODUCTION: Phosphodiesterase type 5 (PDE5) inhibitors act as effective drugs for the treatment of lower urinary tract symptom (LUTS). There is a poor information, however, about the role of the PDE4 inhibitors on the bladder outflow region contractility. AIM: To investigate PDE4 expression and the relaxation induced by the PDE4 inhibitor rolipram versus that induced by the PDE5 blockers sildenafil and vardenafil, in the pig and human bladder neck. METHODS: Immunohistochemistry for PDE4 expression, myographs for isometric force recordings and fura-2 fluorescence for simultaneous measurements of intracellular Ca2+ concentration ([Ca2+]i ) and tension for rolipram in bladder neck samples were used. MAIN OUTCOME MEASURES: PDE4 expression and relaxations to PDE4 and PDE5 inhibitors and simultaneous measurements of [Ca2+]i and tension. RESULTS: PDE4 expression was observed widely distributed in the smooth muscle layer of the pig and human bladder neck. On urothelium-denuded phenylephrine (PhE)-precontracted strips of pig and human, rolipram, sildenafil and vardenafil produced concentration-dependent relaxations with the following order of potency: rolipram> > sildenafil>vardenafil. In pig, the adenylyl cyclase activator forskolin potentiated rolipram-elicited relaxation, whereas protein kinase A (PKA) blockade reduced such effect. On potassium-enriched physiological saline solution (KPSS)-precontracted strips, rolipram evoked a lower relaxation than that obtained on PhE-stimulated preparations. Inhibition of large (BKCa ) and intermediate (IKCa ) conductance Ca2+ -activated K+ channels, neuronal voltage-gated Ca2+ channels, nitric oxide (NO) and hydrogen sulfide (H2 S) synthases reduced rolipram responses. Rolipram inhibited the contractions induced by PhE without reducing the PhE-evoked [Ca2+]i increase. CONCLUSIONS: PDE4 is present in the pig and human bladder neck smooth muscle, where rolipram exerts a much more potent relaxation than that elicited by PDE5 inhibitors. In pig, rolipram-induced response is produced through the PKA pathway involving BKCa and IKCa channel activation and [Ca2+]i desensitization-dependent mechanisms, this relaxation also being due to neuronal NO and H2S release.

Neuronal and non-neuronal bradykinin receptors are involved in the contraction and/or relaxation to the pig bladder neck smooth muscle.

AIMS: The current study investigates the role played by bradykinin (BK) receptors in the contractility to the pig bladder neck smooth muscle. METHODS: Bladder neck strips were mounted in myographs for isometric force recordings and BK receptors expression was also determined by immunohistochemistry. RESULTS: B2 receptor expression was observed in the muscular layer and urothelium whereas B1 expression was consistent detected in urothelium. A strong B2 immunoreactivity was also observed within nerve fibers among smooth muscle bundles. On urothelium-denuded preparations basal tone, BK induced concentration-dependent contractions which were reduced in urothelium-intact samples, by extracellular Ca(2+) removal and by blockade of B2 receptors and voltage-gated Ca(2+) (VOC) and non-VOC channels, and increased by cyclooxygenase (COX) inhibition. On phenylephrine-precontracted denuded strips, under non-adrenergic non-cholinergic (NANC) conditions, electrical field stimulation-elicited frequency-dependent relaxations which were reduced by B2 receptor blockade. In urothelium-intact samples, the B1 receptor agonist kallidin promoted concentration-dependent relaxations which were reduced by blockade of B1 receptors, COX, COX-1 and large-conductance Ca(2+) -activated K(+) (BKCa ) channels and abolished in urothelium-denuded samples and in K(+) -enriched physiological saline solution-precontracted strips. CONCLUSIONS: These results suggest that BK produces contraction of pig bladder neck via smooth muscle B2 receptors coupled to extracellular Ca(2+) entry via VOC and non-VOC channels with a minor role for intracellular Ca(2+) mobilization. Facilitatory neuronal B2 receptors modulating NANC inhibitory neurotransmission and urothelial B1 receptors producing relaxation via the COX-1 pathway and BKCa channel opening are also demonstrated. Neurourol. Urodynam. 33:558-565, 2014. © 2013 Wiley Periodicals, Inc.

Underlying mechanisms involved in progesterone-induced relaxation to the pig bladder neck.

Progesterone increases bladder capacity and improves the bladder compliance by its relaxant action on the detrusor. A poor information, however, exists concerning to the role of this steroid hormone on the bladder outflow region contractility. This study investigates the progesterone-induced action on the smooth muscle tension of the pig bladder neck. To this aim, urothelium-denuded bladder neck strips were mounted in myographs for isometric force recordings and for simultaneous measurements of intracellular Ca(2+) concentration ([Ca(2+)]i) and tension. On phenylephrine (PhE)-precontracted strips, progesterone produced concentration-dependent relaxations only at high pharmacological concentrations. The blockade of progesterone receptors, nitric oxide (NO) synthase, guanylyl cyclase, large conductance Ca(2+)-activated K(+) (BKCa) or ATP-dependent K(+) (KATP) channels reduced the progesterone relaxations. The presence of the urothelium and the inhibition of cyclooxygenase (COX), intermediate- and small-conductance Ca(2+)-activated K(+) channels failed to modify these responses. In Ca(2+)-free potassium rich physiological saline solution, progesterone inhibited the contraction to CaCl2 and to the L-type voltage-operated Ca(2+) (VOC) channel activator BAY-K 8644. Relaxation induced by progesterone was accompanied by simultaneous decreases in smooth muscle [Ca(2+)]i. These results suggest that progesterone promotes relaxation of pig bladder neck through smooth muscle progesterone receptors via cGMP/NO pathway and involving the activation of BKCa and KATP channels and inhibition of the extracellular Ca(2+) entry through L-type VOC channels.

Hydrogen sulfide mediated inhibitory neurotransmission to the pig bladder neck: role of KATP channels, sensory nerves and calcium signaling.

PURPOSE: Because neuronal released endogenous H2S has a key role in relaxation of the bladder outflow region, we investigated the mechanisms involved in H2S dependent inhibitory neurotransmission to the pig bladder neck. MATERIALS AND METHODS: Bladder neck strips were mounted in myographs for isometric force recording and simultaneous measurement of intracellular Ca(2+) and tension. RESULTS: On phenylephrine contracted preparations electrical field stimulation and the H2S donor GYY4137 evoked frequency and concentration dependent relaxation, which was reduced by desensitizing capsaicin sensitive primary afferents with capsaicin, and the blockade of adenosine 5'-triphosphate dependent K(+) channels, cyclooxygenase and cyclooxygenase-1 with glibenclamide, indomethacin and SC560, respectively. Inhibition of vanilloid, transient receptor potential A1, transient receptor potential vanilloid 1, vasoactive intestinal peptide/pituitary adenylyl cyclase-activating polypeptide and calcitonin gene-related peptide receptors with capsazepine, HC030031, AMG9810, PACAP6-38 and CGRP8-37, respectively, also decreased electrical field stimulation and GYY4137 responses. H2S relaxation was not changed by guanylyl cyclase, protein kinase A, or Ca(2+) activated or voltage gated K(+) channel inhibitors. GYY4137 inhibited the contractions induced by phenylephrine and by K(+) enriched (80 mM) physiological saline solution. To a lesser extent it decreased the phenylephrine and K(+) induced increases in intracellular Ca(2+). CONCLUSIONS: H2S produces pig bladder neck relaxation via activation of adenosine 5'-triphosphate dependent K(+) channel and by smooth muscle intracellular Ca(2+) desensitization dependent mechanisms. H2S also promotes the release of sensory neuropeptides and cyclooxygenase-1 pathway derived prostanoids from capsaicin sensitive primary afferents via transient receptor potential A1, transient receptor potential vanilloid 1 and/or related ion channel activation.

Endogenous hydrogen sulfide has a powerful role in inhibitory neurotransmission to the pig bladder neck.

PURPOSE: We investigated the possible involvement of H2S in nitric oxide independent inhibitory neurotransmission to the pig bladder neck. MATERIALS AND METHODS: We used immunohistochemistry to determine the expression of the H2S synthesis enzymes cystathionine γ-lyase and cystathionine ß-synthase. We also used electrical field stimulation and myographs for isometric force recordings to study relaxation in response to endogenously released or exogenously applied H2S in urothelium denuded, phenylephrine precontracted bladder neck strips under noradrenergic, noncholinergic, nonnitrergic conditions. RESULTS: Cystathionine γ-lyase and cystathionine ß-synthase expression was observed in nerve fibers in the smooth muscle layer. Cystathionine γ-lyase and cystathionine ß-synthase immunoreactive fibers were also identified around the small arteries supplying the bladder neck. Electrical field stimulation (2 to 16 Hz) evoked frequency dependent relaxation, which was decreased by DL-propargylglycine and abolished by tetrodotoxin (blockers of cystathionine γ-lyase and neuronal voltage gated Na(+) channels, respectively). The cystathionine ß-synthase inhibitor O-(carboxymethyl)hydroxylamine did not change nerve mediated responses. The H2S donor GYY4137 (0.1 nM to 10 µM) induced potent, concentration dependent relaxation, which was not modified by neuronal voltage gated Na(+) channels, or cystathionine γ-lyase or cystathionine ß-synthase blockade. CONCLUSIONS: Results suggest that endogenous H2S synthesized by cystathionine γ-lyase and released from intramural nerves acts as a powerful signaling molecule in nitric oxide independent inhibitory transmission to the pig bladder neck.

Mechanisms involved in testosterone-induced relaxation to the pig urinary bladder neck.

OBJECTIVES: Testosterone replacement therapy improves bladder capacity in urinary tract dysfunction. There is no information, however, about the role of this steroid hormone on the muscle tension of the bladder outflow region. The current study investigated the mechanisms underlying the testosterone-induced action in the pig bladder neck. METHODS: Urothelium-denuded bladder neck strips were mounted in myographs for isometric force recordings and for simultaneous measurements of intracellular Ca(2+) concentration ([Ca(2+)](i)) and tension. The relaxations to testosterone, the non-aromatizable metabolite 4,5α-dihydrotestosterone (DHT) and electrical field stimulation (EFS) were carried out on phenylephrine (PhE)-precontracted strips. RESULTS: Testosterone and DHT evoked similar concentration-dependent relaxations only at very high pharmacological concentrations. The presence of the urothelium and the inhibition of intracellular androgenic receptor (AR), aromatase, 5α-reductase, nitric oxide (NO) synthase, guanylyl cyclase, cyclooxygenase (COX), large-, intermediate- and small-Ca(2+)-activated K(+) channels or ATP-dependent K(+) channels failed to modify the testosterone relaxations. Neuronal voltage-gated Ca(2+) (VOC) channels and voltage-gated K(+) (K(V)) channel blockers potentiated these responses. EFS evoked frequency-dependent relaxations, which were not changed by threshold concentrations of testosterone. In Ca(2+)-free potassium rich physiological saline solution, testosterone inhibited the contractions induced by CaCl(2) and the L-type VOC channel activator (±)-BAY K 8644. Relaxations elicited by testosterone were accompanied by simultaneous decreases in smooth muscle [Ca(2+)](i). CONCLUSIONS: Testosterone produces relaxation of the pig urinary bladder neck through mechanisms independent of urothelium, AR, aromatase, 5α-reductase, NO synthase, guanylyl cyclase, COX and K(+) channels. Testosterone-induced relaxation is produced via the inhibition of the extracellular Ca(2+) entry through L-type VOC channels.

Mechanisms involved in endothelin-1-induced contraction of the pig urinary bladder neck.

AIMS: There is no information about the signaling pathways involved in the endothelin-1 (ET-1)-induced contraction of bladder neck. The current study investigates the mechanisms involved in the ET-1-elicited contraction in the pig bladder neck. METHODS: Bladder neck strips were mounted in organ baths containing physiological saline solution at 37°C and gassed with 95% O(2) and 5% CO(2) , for isometric force recording to endothelin receptor agonists, noradrenaline (NA), and electrical field stimulation. Endothelin ET(A) receptor expression was also determined, by both immunohistochemistry and Western blot. RESULTS: ET(A) receptor expression (Western blot) was observed in the muscular layer and urothelium. A strong ET(A) -immunoreactivity (ET(A) -IR) was identified within nerve fibers among smooth muscle bundles. ET-1 and ET-2 evoked similar concentration-dependent contractions of urothelium-denuded preparations. ET-3 produced a slight response, whereas the ET(B) receptor agonist BQ3020 failed to promote contraction. BMS182874, an ET(A) receptor antagonist, reduced ET-1-induced contraction whereas BQ788, an ET(B) antagonist, did not change such responses. ET-1 contractions were reduced by extracellular Ca(2+) removal and by inhibition of voltage-gated Ca(2+) (VOC) (L-type) and non-VOC channels, Rho/Rho-kinase pathway, and neuronal VOC channels. NA produced contractions which were enhanced by ET-1 threshold concentrations. ET(A) receptor blockade enhanced nitric oxide-dependent nerve-mediated relaxations. CONCLUSIONS: These results suggest that ET-1 produces contraction via muscular ET(A) receptors coupled to extracellular Ca(2+) entry via VOC (L-type) and non-VOC channels. Intracellular Ca(2+) mobilization and a Rho/Rho-kinase pathway could also be involved in these responses. ET-1-evoked potentiation on noradrenergic contraction, and neuronal ET(A) receptors modulating nitrergic inhibitory neurotransmission, are also demonstrated.

Mechanisms involved in the nitric oxide-induced vasorelaxation in porcine prostatic small arteries.

Benign prostatic hypertrophy has been known to be related with glandular ischemia processes, and nitric oxide (NO) is a potent vasodilator agent. Therefore, the current study investigates the mechanisms underlying the NO-induced vasorelaxation in pig prostatic small arteries. In microvascular myographs, relaxation to electrical field stimulation (EFS), or to exogenous (S)-nitroso-N-acetylpenicillamine (SNAP) and acetylcholine (ACh), was observed on noradrenaline-precontracted prostatic small arterial rings under non-adrenergic and non-cholinergic (NANC) conditions. EFS (1-16 Hz) and exogenous SNAP (0.1-30 µM) evoked frequency- and concentration-dependent relaxation, respectively. Tetrodotoxin, a neuronal voltage-gated Na(+) channel blocker, abolished the EFS-evoked relaxation. ACh (1 nM-10 µM) induced concentration-dependent relaxation, which was reduced by the NO synthase inhibitor N(G)-nitro-L: -arginine (L: -NOARG). L: -NOARG also reduced the EFS-elicited relaxation but failed to modify the response to SNAP. 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and iberiotoxin (IbTX), blockers of soluble guanylyl cyclase and large conductance Ca(2+)-activated K(+) (BK(Ca)) channels, respectively, reduced EFS-, SNAP-, and ACh-induced relaxation. The combination of ODQ with IbTX did not produce further inhibition of the responses to either SNAP or ACh, compared with ODQ alone. Blockade of cyclooxygenases and intermediate and small conductance Ca(2+)-activated, ATP-dependent, and voltage-gated K(+) channels did not change the EFS and SNAP responses. In conclusion, our results suggest that NO and non-NO non-prostanoid factor(s) derived from NANC nerves are involved in the vasodilatation of pig prostatic small arteries. NO produces relaxation through soluble guanylyl cyclase activation-dependent BK(Ca) channel opening and through guanylyl cyclase-independent mechanisms. The vasodilatation elicited by NO could be useful to prevent prostatic ischemia.

Mechanisms involved in the adenosine-induced vasorelaxation to the pig prostatic small arteries.

Benign prostatic hypertrophy has been related with glandular ischemia processes and adenosine is a potent vasodilator agent. This study investigates the mechanisms underlying the adenosine-induced vasorelaxation in pig prostatic small arteries. Adenosine receptors expression was determined by Western blot and immunohistochemistry, and rings were mounted in myographs for isometric force recording. A(2A) and A(3) receptor expression was observed in the arterial wall and A(2A)-immunoreactivity was identified in the adventitia-media junction and endothelium. A(1) and A(2B) receptor expression was not obtained. On noradrenaline-precontracted rings, P1 receptor agonists produced concentration-dependent relaxations with the following order of potency: 5'-N-ethylcarboxamidoadenosine (NECA) = CGS21680 > 2-Cl-IB-MECA = 2-Cl-cyclopentyladenosine = adenosine. Adenosine reuptake inhibition potentiated both NECA and adenosine relaxations. Endothelium removal and ZM241385, an A(2A) antagonist, reduced NECA relaxations that were not modified by A(1), A(2B), and A(3) receptor antagonists. Neuronal voltage-gated Ca(2+) channels and nitric oxide (NO) synthase blockade, and adenylyl cyclase activation enhanced these responses, which were reduced by protein kinase A inhibition and by blockade of the intermediate (IK(Ca))- and small (SK(Ca))-conductance Ca(2+)-activated K(+) channels. Inhibition of cyclooxygenase (COX), large-conductance Ca(2+)-activated-, ATP-dependent-, and voltage-gated-K(+) channel failed to modify these responses. These results suggest that adenosine induces endothelium-dependent relaxations in the pig prostatic arteries via A(2A) purinoceptors. The adenosine vasorelaxation, which is prejunctionally modulated, is produced via NO- and COX-independent mechanisms that involve activation of IK(Ca) and SK(Ca) channels and stimulation of adenylyl cyclase. Endothelium-derived NO playing a regulatory role under conditions in which EDHF is non-functional is also suggested. Adenosine-induced vasodilatation could be useful to prevent prostatic ischemia.