Effects of ethacrynic acid on Schlemm's canal inner wall and outflow facility in human eyes.
(73/6480)
PURPOSE: The role of the inner wall of Schlemm's canal in determining aqueous outflow facility is poorly understood. To quantify the relationship between inner wall pore characteristics and aqueous outflow facility in human eyes, both control eyes and eyes in which facility had been pharmacologically increased by ethacrynic acid (ECA) infusion were studied. METHODS: Outflow facility was measured in enucleated human eyes before and after delivery of 0.25 mM ECA (one eye of each of 6 pairs) or 2.5 mM ECA (one eye of each of 13 pairs). ECA, and vehicle in contralateral eyes, was delivered into Schlemm's canal by retroperfusion, thereby largely avoiding drug exposure to the trabecular meshwork. After facility measurement, eyes were fixed under conditions of either constant pressure (physiological intraocular pressure, 13 pairs) or "equal flow" (6 pairs) and were microdissected to expose the inner wall of Schlemm's canal. The density and diameter of intercellular and intracellular inner wall pores were measured using scanning electron microscopy. RESULTS: Retroperfusion with 2.5 mM ECA increased facility by 73% (P < 0.001), whereas 0.25 mM ECA increased facility by 19% (not statistically significant). The density of intercellular pores in the inner wall of Schlemm's canal was increased by 520% in 2.5 mM ECA-retroperfused eyes (P < 0.00004), whereas intracellular pore density remained approximately constant. Large pores (size > or = 1.1 microm) were particularly enhanced in ECA retroperfused eyes. The net change in facility due to ECA was not correlated with changes in pore density or other inner wall pore statistics. CONCLUSIONS: Our data are most consistent with a model in which pores in the inner wall of Schlemm's canal indirectly influence facility. However, measured changes in facility due to changes in inner wall properties did not agree with quantitative predictions of the pore funneling theory, suggesting that changes in facility may instead be due to gel leakage from the extracellular spaces of the juxtacanalicular tissue. More definitive experiments are required to confirm this hypothesis. (+info)
Naftopidil, a novel alpha1-adrenoceptor antagonist, displays selective inhibition of canine prostatic pressure and high affinity binding to cloned human alpha1-adrenoceptors.
(74/6480)
The pharmacological profiles of the alpha1-adrenoceptor antagonists naftopidil, tamsulosin and prazosin were studied in an anesthetized dog model that allowed the simultaneous assessment of their antagonist potency against phenylephrine-mediated increases in prostatic pressure and mean blood pressure. The intravenous administration of each of these compounds dose-dependently inhibited phenylephrine-induced increases in prostatic pressure and mean blood pressure. To further assess the ability of the three compounds to inhibit phenylephrine-induced responses, the doses required to produce a 50% inhibition of the phenylephrine-induced increases in prostatic and mean blood pressure and the selectivity index obtained from the ratio of those two doses were determined for each test compound. Forty minutes after the intravenous administration of naftopidil, the selectivity index was 3.76, and those of tamsulosin and prazosin were 1.23 and 0.61, respectively. These findings demonstrated that naftopidil selectively inhibited the phenylephrine-induced increase in prostatic pressure compared with mean blood pressure in the anesthetized dog model. The selectivity of naftopidil for prostatic pressure was the most potent among the test compounds. In addition, using cloned human alpha1-adrenoceptor subtypes, naftopidil was selective for the alpha1d-adrenoceptor with approximately 3- and 17-fold higher affinity than for the alpha1a- and alpha1b-adrenoceptor subtypes, respectively. The selectivity of naftopidil for prostatic pressure may be attributable to its high binding affinity for alpha1a- and alpha1d-adrenoceptor subtypes. (+info)
Visual parameters define the phase and the load of contractions in isolated guinea pig ileum.
(75/6480)
How the movements of the intestinal walls relate to luminal pressures and outflow remains incompletely understood. We triggered the peristaltic reflex in the isolated ileum of the guinea pig and quantified wall movements through computerized measurements of diameter changes. Contractions developed as indentations close to the upstream end of the loop. The indentations deepened and expanded in length. The downstream shoulder of contractions started and stopped to propagate before the upstream shoulder. Shoulders differed in their length and gradient over most of the duration of the contraction, and this gives the contraction an axial asymmetry. Over the course of individual contractions, the length of the indented segment correlated well with the luminal pressure. Contractions in response to large volumes generated long indented segments and high luminal pressures. The onset and the end of pressure waves and of outflow did not necessarily coincide with the onset and end of visual parameters of contractions. These findings indicate that objective visual parameters might be useful to describe and to classify contractions. (+info)
Characterization of a newly found stretch-activated KCa,ATP channel in cultured chick ventricular myocytes.
(76/6480)
With the use of the patch-clamp technique, five kinds of stretch-activated (SA) ion channels were identified on the basis of their single-channel conductances and ion selectivities in cultured chick ventricular myocytes. Because a high-conductance K+-selective channel predominated among these channels, we concentrated on characterizing its properties mostly using excised inside-out patches. With 145 mM KCl solution in the pipette and the bath, the channel had a conductance of 199.8 +/- 8.2 pS (n = 22). The ion selectivities among K+, Na+, Ca2+, and Cl- as estimated from their permeability ratios were PNa/PK = 0.03, PCa/PK = 0.025, and PCl/PK = 0.026. The probability of the channel being open (Po) increased with the Ca2+ concentration in the bath ([Ca2+]b; dissociation constant Kd = 0.51 microM at +30 mV) and membrane potential (voltage at half-maximal Po = 39.4 mV at 0.35 microM [Ca2+]b). The channel was blocked by gadolinium, tetraethylammonium, and charybdotoxin from the extracellular surface and, consequently, was identified as a Ca2+-activated K+ (KCa) channel type. The channel was also reversibly activated by ATP applied to the intracellular surface (Kd = 0.74 mM at 0.10 microM [Ca2+]b at +30 mV). From these data taken together, we concluded that the channel is a new type of KCa channel that could be designated as an "SA KCa,ATP channel." To our knowledge, this is the first report of KCa channel in heart cells. (+info)
Threshold for efferent bladder nerve firing in the rat.
(77/6480)
In this study, the mechanism involved in the initiation of voiding was investigated. Bladder pressure and bladder and urethral nerve activity were recorded in the anesthetized rat. Bladder nerve activity was resolved into afferent and efferent activity by means of a theoretical model. The beginning of an active bladder contraction was defined as the onset of bladder efferent firing at a certain time (t0). From t0 onward, bladder efferent activity increased linearly during deltat seconds (rise time) to a maximum. The pressure at t0 was 1.0 +/- 0.4 kPa, the afferent nerve activity at t0 was 2.0 +/- 0.6 microV (53 +/- 15% of maximum total nerve activity), and deltat was 11 +/- 13 s. Between contractions the afferent activity at t0 was never exceeded. Urethral afferent nerve activity started at bladder pressures of 2.1 +/- 1.1 kPa. Therefore, we concluded that urethral afferent nerve activity does not play a role in the initiation of bladder contractions; voiding contractions presumably are initiated by bladder afferent nerve activity exceeding a certain threshold. (+info)
Maximum static respiratory pressures in healthy elderly men and women: issues of reproducibility and interpretation.
(78/6480)
BACKGROUND: Respiratory muscle strength is assessed using the static pressure generated at the mouth during a maximal inspiratory or expiratory effort [PImax and PEmax, respectively (MSRPs)]. Interpretation of MSRPs relies upon comparison with 'normal' values, but MSRPs show very weak associations with predictors such as physical characteristics. The influence of habitual physical activity upon MSRPs remains undefined. OBJECTIVES: We examined measurement reproducibility, as well as the influence of physical characteristics and habitual physical activity upon MSRPs in healthy elderly people. METHODS: MSRPs were assessed in 41 healthy subjects using a portable mouth pressure meter on two occasions, 1 week apart. Physical activity was assessed in 10 subjects by diary record. Pearson product-moment correlation coefficients were used to assess the association of MSRPs with other measured variables. RESULTS: There was good measurement reproducibility of MSRPs, with coefficients of reproducibility of 10.2 and 12.8% for PImax and PEmax, respectively. MSRPs showed statistically significant negative correlations with age, but correlations with physical characteristics were poor. In contrast, MSRPs were highly correlated with physical activity. CONCLUSIONS: We conclude that MSRPs can be measured reproducibly and that they decline with advancing age. Physical characteristics are not good predictors of MSRPs; this may be due to a strong confounding influence of physical activity making interpretation of measurements problematic. We suggest that the poor predictive power of physical characteristics indicate that reference to 'normal' values be made with caution and that it may be more appropriate to consider functional interpretations of MSRPs based upon factors such as lung and chest wall elastance. (+info)
Decrease in lung volume depends on end-expiratory pressure in a rabbit model of airway lavage.
(79/6480)
BACKGROUND: In the past, the rabbit model of repeated airway lavage has been extensively used to induce a decrease in lung volume accompanied by impairment in lung mechanics and gas exchange. OBJECTIVES: The rationale of our study was to investigate the influence of different end-expiratory pressure (EEP) levels (0.4-4.2 cm H2O) on changes in functional residual capacity (FRC) and the efficacy of lavages administered. METHODS: Forty-five rabbits were subjected to 2-8 lavages with 20 ml/kg warm normal saline until arterial/alveolar oxygen tension (a/A ratio) had decreased to +info)
Simultaneous pyloric and colonic obstruction associated with hiatus hernia in a weightlifter: a case report.
(80/6480)
Hiatus hernia is usually attributed to conditions that cause a chronic increase in intra-abdominal pressure such as multiple pregnancies and obesity. A 30-year-old man, a weightlifter, had a massive hiatus hernia causing both high and low gastrointestinal obstruction but no involvement of the gastroesophageal junction or fundus. The onset of the obstruction is attributed to an extreme increase in intra-abdominal pressure caused by the action of lifting weights. (+info)