Characterization of the Na/HCO3(-) cotransport in human neutrophils.

BACKGROUND: Bicarbonate transport has crucial roles in regulating intracellular pH (pHi) in a variety of cells. The purpose of this study was to evaluate its participation in the regulation of pHi in resting and stimulated human neutrophils. METHODS: Freshly isolated human neutrophils acidified by an ammonium prepulse were used in this study. RESULTS: We demonstrated that resting neutrophils have a bicarbonate transport mechanism that prevents acidification when the Na(+)/H(+) exchanger is blocked by EIPA. Neutrophils acidified by an ammonium prepulse showed an EIPA-resistant recovery of pHi that was inhibited by the blocker of the anionic transporters SITS or the Na(+)/HCO3(-) cotransporter (NBC) selective inhibitor S0859, and abolished when sodium was removed from the extracellular medium. In western blot and RT-PCR analysis the expression of NBCe2 but not NBCe1 or NBCn1 was detected in neutrophils Acidified neutrophils increased the EIPA-insensitive pHi recovery rate when its activity was stimulated with fMLF/ cytochalasin B. This increase in the removal of acid equivalents was insensitive to the blockade of the NADPH oxidase with DPI. CONCLUSION: It is concluded that neutrophils have an NBC that regulates basal pHi and is modulated by chemotactic agents.

Cl⁻/HCO3⁻ exchange activity in fMLP-stimulated human neutrophils.

It is well known that chemotactic agents active Na(+)/H(+) exchanger, increasing intracellular pH of neutrophils, but their effect on bicarbonate transporters have not been established yet. To study the effect of fMLP on the activity of Cl(-)/HCO(3)(-) exchange, the rate of pH recovery after acute Cl(-) readmission in cell subjected to an alkaline load by CO(2) washout in a Cl-free medium was measured. The activity of the exchanger was reduced to 72% of control when cells were pre-incubated for 5 min with 0.1 µM fMLP and reached 48% of control in steady state after acute exposure. After extracellular bicarbonate or TMA addition the rate recovery of intracellular pH was reduce at 72% and at 84%, respectively. The inhibitory effect on the intracellular pH recovery was not affected by blockers of Na(+)/H(+) exchange. We conclude from these studies that an increase of pH(i) produced for this chemotactic agent is facilitated by the simultaneous activation of Na(+)/H(+) exchange and inhibition of Cl(-)/HCO(3)(-) exchange in neutrophils.

Effect of glycine on the release of reactive oxygen species in human neutrophils.

The increase of extracellular glycine concentration prevents or mitigates a variety of pathological dysfunctional inflammatory responses. To eliminate the systemic effects of glycine as the reduction in the release of cytokines, this study was performed in isolated human neutrophils. The increase of the intracellular calcium concentration ([Ca2+](i)) and reactive oxygen species (ROS) release in cells incubated with glycine (0.1 to 10 mM) and stimulated with fMLP or PMA were compared with glycine-free controls. Glycine inhibited ROS production but increased [Ca2+](i) signal produced by fMLP. The inhibition of ROS production was observed even when glycine was added after the ROS release had reached maximal rate. The inhibitory effect was insensitive to strychnine and also obtained when PMA was used as stimulant. This study demonstrated that glycine impaired the activation of oxidative burst independently of glycine-gated chloride channel, presumably at the membrane level.

Inhibition of cytochalasin-primed neutrophils by hyperosmolarity.

Experimental and clinical investigations using hyperosmotic solutions for resuscitation of hemorrhagic shock demonstrated modulation of the inflammatory response. Decreased postinjury hyperinflammation has been attributed to a reduction in neutrophil-mediated tissue damage. This study shows that cytoskeletal disruption with cytochalasinB did not reverse or prevent the inhibitory effect of an osmolarity increase on the neutrophil cytotoxic response to a formyl peptide. In cytochalasin-primed neutrophils, the hyperosmolarity-dependent inhibition promptly reversed after returning to iso-osmotic levels. Paradoxically, an increase in osmolarity after stimulation produced an increase in the release of reactive oxygen species to the extracellular medium. The inhibitory effect of hyperosmotic NaCl can be reproduced by solutions of similar osmolarity containing N-methyl glucamine or sucrose, but solutions containing mannitol allowed an almost complete response to N-formyl methionyl leucyl phenylalanine. The effects on the release of reactive oxygen species to the extracellular media found with the OxyBURST-bovine serum albumin assay correlated with the changes of the intracellular calcium signal, indicating that the inhibition by hyperosmolarity occurs near the receptor level.

Hydrogen peroxide activates calcium influx in human neutrophils.

The correlation between an increased production of reactive oxygen species (ROS) and an enhanced calcium entry in primed neutrophils stimulated with fMLP suggests that endogenous ROS could serve as an agonist to reinforce calcium signaling by positive feedback. This work shows that exogenous H2O2 produced a rapid influx of Mn2+ and an increase of intracellular calcium. The H2O2 was insufficient to produce significant changes in the absence of extracellular calcium but addition of Ca2+ to H2O2-treated cells suspended in a free Ca2+/EGTA buffer resulted in a great increase in [Ca2+]i reflecting influx of Ca2+ across the cell membrane. The increase of intracellular calcium was inhibited by Ni2+, La3+, and hyperosmotic solutions of mannitol and other osmolytes. This raises the possibility that the secretion of H2O2 by activated neutrophils could act as an autocrine regulator of neutrophil function through the activation of calcium entry.

Effect of glycine on the calcium signal of thrombin-stimulated platelets.

In treatment of hemorrhagic shock, small-volume infusion of 7.5% NaCl gives immediate hemodynamic improvement, but in vitro experiments suggest it depresses the hemostatic system. Since previous reports showed that hyperosmotic glycine solutions preserved the platelet function better than hyperosmotic NaCl solutions, we investigated whether glycine changes the intracellular calcium ([Ca]i) signal. Platelets were incubated in hyperosmotic solutions containing sodium glycine or glycine base and stimulated with 0.1 IU/ml thrombin. [Ca]i increases were compared with an isosmotic control. Platelets incubated in zero calcium/EGTA were used to study separately the effect of glycine on calcium mobilization from intracellular stores and extracellular calcium entry. When NaCl was replaced by sodium glycine, the [Ca]i increase produced by thrombin was enhanced, because the calcium entry increased without changes in the mobilization of stored calcium. The addition of 50 mmol/l glycine base to the HEPES-buffered media increases the thrombin-induced entry of calcium or manganese. This study demonstrates that hyperosmotic glycine solutions increase the entry of calcium. This effect contrasts with the impairment of the thrombin-induced calcium signals by NaCl. The addition of low amounts of glycine in resuscitation solutions would be useful to reduce dysfunctional inflammatory responses without the risk of bleeding; however, concentrated solutions could cause toxic effects.

Selective inhibition of calcium influx by 2-aminoethoxydiphenyl borate.

2-aminoethoxydiphenyl borate (2APB) blocks agonist-induced Ca2+ mobilization from intracellular stores and Ca2+ entry. To compare the sensitivity profiles of these two components of calcium signaling, human platelets were exposed to different concentrations of 2APB. The drug interferes with the Ca2+ mobilization from intracellular stores induced by thrombin with an IC50 of 52+/-2 microM but it has a more potent inhibitory effect on the Ca2+ entry (IC50=16+/-1 microM). This value was similar to the IC50 found when the immediate inhibition of the calcium entry was studied after Ca2+ mobilization was completed (IC50=18+/-5 microM). The calcium influx induced by thapsigargin showed an IC50 of 17+/-1 microM for the immediate inhibition. The sensitivity to bivalent ion entry to 2APB was confirmed by Mn2+ entry inhibition. Although the specificity of 2APB with respect to the intracellular signaling system has not been fully established, our results confirm that the direct inhibition of calcium entry through the store-operated channels requires lower concentrations than the inhibition of mobilization, suggesting an independent and different site of action.

Multiple alterations in Ca2+ handling determine the negative staircase in a cellular heart failure model.

BACKGROUND: The flat or negative force frequency relationship (FFR) is a hallmark of the failing heart. Either decreases in SERCA2a expression, increases in Na(+)/Ca(2+) exchanger (NCX) expression or elevated Na(+)(i) have been independently proposed as mediators of the negative FFR. METHODS AND RESULTS: To determine whether each one of these mechanisms is sufficient to account for the negative FFR of the failing heart or on the contrary, various mechanisms, acting in concert are required. SERCA2a was pharmacologically inhibited with thapsigargin (TG) or cyclopiazonic acid (CPA) or by using siRNA technology; Na(+)(i) was increased with either ouabain (Oua) or monensin and NCX protein was overexpressed by gene transfer (Ad.NCX), to mimic in nonfailing cat myocytes the phenotype of the failing heart and examine their effect on the FFR. The positive FFR of healthy myocytes remained unaffected after either SERCA2a inhibition, Na(+)(i) elevation, or NCX overexpression. However, the combination of TG + Oua, Oua + Ad.NCX, or TG + Ad.NCX, converted the positive FFR to negative. Moreover, the FFR became negative at lower frequencies, when the 3 interventions were combined. CONCLUSIONS: Ca(2+) handling has to be altered at several levels to explain the negative FFR of the failing heart. These anomalies in Ca(2+) homeostasis acting in synergy have additive effects.

Functional interaction of carbonic anhydrase and chloride/bicarbonate exchange in human platelets.

Recently, our laboratory has reported the presence of one acidifying Cl-/HC exchange mechanism in human platelets. This paper demonstrates that this exchanger decreases its activity after inhibition of carbonic anhydrase. BCECF-loaded platelets, previously equilibrated in a bicarbonate/CO2 buffered solution, were resuspended in a Hepes-buffered, chloride-free (glucuronate) medium to produce a pHi increase. After addition of 50 mM NaCl, pHi fell rapidly reaching steady state in the succeeding 400 s. The recovery in chloride-containing solution was in contrast to the effect of a similar change in osmolarity by addition of 50 mM sodium glucuronate that produced a significantly slower variation of pHi. Alkali loads produced by 25 mM TMA were also counteracted by HC equivalent efflux via Cl-/HC exchange. The present study shows that the efflux of HC was slower when the platelets were previously incubated in 100 microM methazolamide. As a conclusion, the recovery of pHi from alkalosis by Na-independent Cl-/HC exchange is facilitated in platelets by the enzymatic activity of the carbonic anhydrase.

Thrombin stimulation of Cl-/HCO3- exchange in human platelets.

The presence of one acidifying Cl-/HCO3- exchange mechanism in human platelets has not been previously reported. This paper demonstrates that this mechanism does function and that it increases its activity after stimulation with thrombin. On resuspension of BCECF-loaded platelets in a chloride-free medium (gluconate replaced) that contains bicarbonate, cytosolic pH (pHi) increased and stabilized after 10 min at an alkaline value. After addition of 50 mM NaCl, pHi fell rapidly reaching steady state in the succeeding 5 min. The stilbene derivative 4-acetamido-4'-isothiocyanato stilbene-2,2' disulfonic acid (SITS) inhibited both, the alkalization in chloride-poor solution and the recovery from the alkaline load after chloride enrichment. The decline in pHi was observed whether chloride was delivered to the solution in the form of LiCl or NaCl, or when the later was applied after blockage of the Na+/H+ exchanger. The recovery in chloride-containing solution was in contrast to the effect of a similar change in osmolarity by addition of 50 mM sodium gluconate that did not produced a significant variation of pHi. Posterior addition of NaCl after 5 min in high gluconate reproduced the pHi fall of the control experiment. Alkali loads produced by 25 mM trimethylamine hydrochloride (TMA) were also counteracted by HCO(3-)-equivalent efflux via Cl-/HCO3- exchange. One of the major observations of the present study is that HCO3- equivalent efflux was twice as high when the platelets were previously stimulated with 0.1 IU of thrombin, but thrombin did not produce significant changes of the pHi recovery rate in a bicarbonate-free solution. The increase of the decline in pHi elicited by preexposure to thrombin was still observed in the presence of an inhibitor of the Na+/H+ exchange or in sodium-free solutions. It is concluded that a Na-independent Cl-/HCO3- exchange mechanism mediates the recovery of pHi from alkalosis in platelets and that thrombin activates this exchanger by a direct regulatory pathway.

Carbon monoxide inhibits capacitative calcium entry in human platelets.

The cytosolic calcium concentration in human platelets is elevated by several agonists via receptor-operated mechanisms involving both Ca(2+) release from intracellular stores and Ca(2+) entry. In order to get a mechanistic insight in the effect of carbon monoxide (CO)-containing solutions, this work examines the changes in [Ca(2+)](i) induced by 100 microM adenosine 5'diphosphate (ADP), 0.1 IU/ ml thrombin, 0.5 microM thapsigargin or 0.5 microM ionomycin in human platelets. In a saline solution bubbled with CO, the increase of [Ca(2+)](i) produced by thrombin was 72+/-4% of the response evoked in the control solution (CO-free) and the response elicited by ADP was 64+/-8% of the control. When a mixture of 5% CO/95% N(2) was used, the responses were 70+/-7% of control for thrombin and 79+/-6% of control for ADP. The mobilization of stored calcium produced by thrombin in a calcium-free solution and the increase of [Ca(2+)](i) produced by subsequent introduction of 1 mM extracellular calcium were both reduced in the presence of CO (82+/-6% and 78+/-5% of control, respectively). Similar reductions in the presence of CO were found when platelets were stimulated by ADP (62+/-8% and 60+/-8% for mobilization in calcium-free media and calcium entry, respectively). Although the change in [Ca(2+)](i) induced by ionomycin in the presence of extracellular calcium was almost the same in the absence or presence of CO (97+/-5% of control), the entry induced by depletion of reservoirs with the ionophore undergoes a significant reduction in a solution bubbled with CO (84+/-5% of control). In agreement with the concept that CO has a direct inhibitory effect on capacitative calcium entry, a reduction to 47+/-6% of control was obtained when sarco/endoplasmic reticulum ATPase was blocked by thapsigargin. Diverse mechanisms could be responsible for the effect of CO on calcium entry. On the one hand, a decrease in the calcium release from intracellular stores or an increase in the rate of its back-sequestration could occur, being the reduction of capacitative calcium entry an indirect consequence of a diminished emptying of reservoirs. On the other hand, CO could have a direct inhibitory effect on the pathway that produces the calcium entry. The decrease in the Ca(2+) signal in the presence of CO evoked by receptor-independent emptying of reservoirs indicates that a direct effect of CO on capacitative calcium entry participates in the antiaggregatory properties of CO. The proposal that CO inhibits directly store-operated calcium influx widens the potential mechanisms by which heme oxygenase regulates cell functions.

Hypertonic saline solutions attenuate agonist-induced changes of intracellular calcium.

The proper fluid for resuscitation of hemorrhagic shock is still controversial. Hypertonic saline solutions would cause an impairment of platelet function, aggravating blood loss in case of uncontrolled hemorrhage. This work examines the in vitro effect of hypertonic NaCl solutions on the changes in [Ca2+]i induced by 100 microM ADP, 0.1 IU/ml thrombin or 0.5 microM ionomycin in human platelets. Furthermore, it was investigated if the addition of NaCl reduces the mobilization from intracellular stores or the calcium entry from extracellular media. In a solution containing 1 mM CaCl2, the increase of [Ca2+]i produced by thrombin was 93, 75 or 55% of the 300 mosM control when osmolarity of the solution was 350, 400, or 500 mosM, respectively. The calcium signal induced by ADP decreased more rapidly in hypertonic media than in isotonic solution. In a calcium-free solution, the mobilization of stored calcium produced by thrombin was reduced when osmolarity was increased from 300 mosM to 350, 400 or 500 mosM by 86, 75 or 45% of the control, respectively. The increase of [Ca2+]i produced by subsequent introduction of 1 mM extracellular calcium was also reduced. Similar effects were found when platelets were stimulated by ADP. Instead, the capacitative calcium entry induced by ionomycin was increased in 500 mosM media by a 138% of the isotonic control. The decrease in the Ca2+ signal produced by receptor agonists in hypertonic media may play a role in the reduction of platelet responses such as aggregation or shape change when hypertonic resuscitation fluids are utilized.

Effect of hyperosmolarity on agonist-induced increases of intracellular calcium in human platelets.

BACKGROUND: Hypertonic solutions are useful for the management of hypovolemic shock but cause impairment in platelet function. This effect would reduce the ischemia/reperfusion damage caused by activated platelets, but it could be the cause of aggravating blood loss in case of uncontrolled hemorrhage. In this paper, it was studied if osmotic shrinkage of platelets affects the changes in intracellular calcium concentration ([Ca(2+)](i)) induced by thrombin or adenosine 5' diphosphate (ADP). Furthermore, it was investigated if hypertonic solutions change the mobilization from intracellular stores or the calcium entry. Previous reports from our laboratory described that the capacitative calcium entry is increased by alkalization and also that hyperosmolarity has an alkalinizing effect on human platelets so it was hypothesized that hyperosmolarity would be able to modify agonist-induced calcium entry. MATERIAL AND METHODS: To study the response to agonists, platelets loaded with 2'7'-bis(carboxyethyl)-5(6)-carboxy-fluorescein (FURA 2) were incubated at 37 degrees C for 500 s in a N-2-hidroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered solution with 1 mM CaCl(2). The osmolarity of the solution was elevated by the addition of 200 mM mannitol or sucrose and after the stimulation with 0.1 IU/ml of thrombin or 100 microM ADP, [Ca(2+)](i) increases were compared. Platelets incubated in zero calcium/EGTA were stimulated with these agonists or with 0.1 microM thapsigargin to separately study the effect of hyperosmolarity on both calcium mobilization from intracellular stores and extracellular calcium entry. RESULTS: It was found that hypertonic solutions decrease the [Ca(2+)](i) peak induced by the agonist: The increase of [Ca(2+)](i) in the presence of 200 mM mannitol produced by 100 microM ADP was 62+/-6% and response to 0.1 IU/ml thrombin was 74+/-7% of the increase in isotonic control solution. In the case of ADP, both mobilization and calcium entry were reduced to 66+/-3% and 65+/-6% of isotonic control, respectively. In the case of thrombin, only the mobilization showed a significant change (79+/-2% of parallel control). In platelets depleted by thapsigargin, the capacitative calcium entry was increased in hypertonic mannitol (174+/-25% of the isotonic control). Similar results were obtained with hypertonic sucrose solutions. CONCLUSIONS: In spite of the stimulatory effect of hyperosmolarity on capacitative calcium entry observed in platelets in which the calcium stores were depleted with thapsigargin, the full response of intracellular calcium to the agonists tested (ADP and thrombin) was reduced by an increase in osmolarity. The decreased Ca(2+) mobilization observed may play a role in the reduction in hypertonic media of accompanying platelets responses such as aggregation or shape change.

Capacitative calcium influx and intracellular pH cross-talk in human platelets.

This study focuses on the potential interrelationships between changes in pH and capacitative calcium entry in stimulated platelets and on the participation of SOCs in the control of intracellular pH (pH(i)). Extracellular acidification reduces the Mn(2+) entry, measured by the slope of the quenching of FURA 2 fluorescence at the isoemissive wavelength of 360 nm. In thrombin-stimulated platelets Mn(2+) entry is reduced by acidosis (pH(o) = 6.89) to 17 +/- 4% of control (pH(o) = 7.32). In platelets treated with thapsigargin (TG) to induce the opening of store-operated channels (SOCs) the rate of quenching was reduced by acidosis to 31 +/- 5 % of control. Calcium entry was measured as the peak of [Ca(2+)](i) response to extracellular calcium readmission after mobilization of calcium from intracellular stores. Changes in pH(o) of platelet suspension media markedly alters the calcium entry evoked by thrombin that reach a 16 +/- 6 % of control in acidosis (pH(o) = 6.89) and 150 +/- 15% of control in alkalosis (pH(o) = 7.62). The SERCA inhibitor TG was used to study the effect of pH(o) on Ca(2+) influx. Acidosis decreases and alkalosis increases the capacitative calcium entry to 22 +/- 4 % and 129 +/- 1% of control respectively. These changes in pH(o) also produced changes in pH(i). Treatment of platelets with titrated solutions of trimethylamine causes intracellular alkalinization without changes in pH(o) increasing the capacitative calcium entry to 120 +/- 5%. TG itself produces an intracellular alkalinization that is further increased by calcium entry. Blockage of the Na(+)/H(+) exchanger reverted TG effect on pH(i) without changes in capacitative calcium entry.

Prevalencia de hipertension arterial en 3154 jovenes estudiantes / Prevalence of hypertension in 3154 young students

Se realizó un estudio de corte transversal durante los años 1993-97 para determinar la prevalencia de hipertensión arterial (HTA) en estudiantes de la Facultad de Ciencias Médicas de la Universidad Nacional de La Plata. Fueron entrevistados 3154 jóvenes (edad media 21 años) de ambos sexos. Se realizaron tres determinaciones de la presión arterial (PA) en cada individuo en una única ocasión, y se utilizó el promedio de las tres para establecer la prevalencia de HTA. La prevalencia global de HTA (PA = 140 y/o 90 mm Hg) fue de 12 por ciento, siendo para los varones de 20 por ciento y para las mujeres de 6 por ciento. La diferencia entre los dos sexos fue estadísticamente significativa (p < 0.001). La PA sistólica (PAS) y la PA diastólica (PAD) promedio en mujeres y varones fueron significativamente distintas (115 + 11 / 74 + 9 mm Hg en mujeres y 126 + 13 / 77 + 10 mm Hg en varones; p < 0.0001). Si para definir HTA considerásemos los valores de PA del percentilo 95 en cada sexo (148/93 mm Hg en varones y 133/88 mm Hg en mujeres), el límite entre normo e HTA sería diferente en varones y mujeres. La prevalencia de HTA que hallamos en este grupo etáreo fue muy alta si la comparamos con la hallada en los últimos años para el mismo grupo en Estados Unidos (NHANES III, 2 por ciento); en cambio, es prácticamente la misma que la de EE.UU a fines de los 70 (NHANES II, 12 por ciento), antes de intensificarse en dicho país las acciones de prevención primaria de HTA. La prevalencia de indivíduos con PA óptima (PA < 120/80 mm Hg) fue de sólo el 44 por ciento en este estudio. La correlación entre el índice de masa corporal (IMC) y los níveles de PA media (PAM) fue positiva y con un r = 0.33 (p < 0.0001). La PAM se incrementó a razón de 1.16 mm Hg por cada unidad de aumento en el IMC. Se interrogó a los alumnos acerca de la presencia de antecedentes familiares (únicamente madre o padre) de HTA y no se detectaron diferencias significativas entre los estudiantes hipertensos y los no hipertensos. Considerando que la principal causa de muerte en nuestro medio son las enfermedades cardiovasculares, y que la HTA es uno de los factores de riesgo más importantes para su desarrollo, esta alta prevalencia de HTA en la población joven resulta un llamado de alerta impostergable. (AU)

Prevalencia de hipertension arterial en 3154 jovenes estudiantes / Prevalence of hypertension in 3154 young students

Se realizó un estudio de corte transversal durante los años 1993-97 para determinar la prevalencia de hipertensión arterial (HTA) en estudiantes de la Facultad de Ciencias Médicas de la Universidad Nacional de La Plata. Fueron entrevistados 3154 jóvenes (edad media 21 años) de ambos sexos. Se realizaron tres determinaciones de la presión arterial (PA) en cada individuo en una única ocasión, y se utilizó el promedio de las tres para establecer la prevalencia de HTA. La prevalencia global de HTA (PA = 140 y/o 90 mm Hg) fue de 12 por ciento, siendo para los varones de 20 por ciento y para las mujeres de 6 por ciento. La diferencia entre los dos sexos fue estadísticamente significativa (p < 0.001). La PA sistólica (PAS) y la PA diastólica (PAD) promedio en mujeres y varones fueron significativamente distintas (115 + 11 / 74 + 9 mm Hg en mujeres y 126 + 13 / 77 + 10 mm Hg en varones; p < 0.0001). Si para definir HTA considerásemos los valores de PA del percentilo 95 en cada sexo (148/93 mm Hg en varones y 133/88 mm Hg en mujeres), el límite entre normo e HTA sería diferente en varones y mujeres. La prevalencia de HTA que hallamos en este grupo etáreo fue muy alta si la comparamos con la hallada en los últimos años para el mismo grupo en Estados Unidos (NHANES III, 2 por ciento); en cambio, es prácticamente la misma que la de EE.UU a fines de los '70 (NHANES II, 12 por ciento), antes de intensificarse en dicho país las acciones de prevención primaria de HTA. La prevalencia de indivíduos con PA óptima (PA < 120/80 mm Hg) fue de sólo el 44 por ciento en este estudio. La correlación entre el índice de masa corporal (IMC) y los níveles de PA media (PAM) fue positiva y con un r = 0.33 (p < 0.0001). La PAM se incrementó a razón de 1.16 mm Hg por cada unidad de aumento en el IMC. Se interrogó a los alumnos acerca de la presencia de antecedentes familiares (únicamente madre o padre) de HTA y no se detectaron diferencias significativas entre los estudiantes hipertensos y los no hipertensos. Considerando que la principal causa de muerte en nuestro medio son las enfermedades cardiovasculares, y que la HTA es uno de los factores de riesgo más importantes para su desarrollo, esta alta prevalencia de HTA en la población joven resulta un llamado de alerta impostergable.

Niveles de presion arterial en jóvenes estudiantes: correlacion con la masa corporal, factores metabólicos y hemodinámicos / Blood pressure levels in young students: correlation between body mass, metabolic and hemodynamic factors

En un grupo homogéneo de 450 estudiantes (20,8 + 0,11 años) se examinaron los niveles de presión arterial (PA) y se correlacionaron con diferentes parámetros. La prevalencia de hipertensión arterial fue, según el criterio del JNC-V, 13 por ciento en varones y 3 por ciento en mujeres. Las correlaciones entre índice de masa corporal (IMC) y niveles de PA fueron estadísticamente significativas en varones y mujeres. La presión arterial media (PAM) aumentó a razón de 1.17 mmHg por cada unidad de incremento en el IMC en los varones y 0.97 mmHg en las mujeres. En base a los niveles de PA propuestos por el JNC-V se seleccionaron tres grupos: varones con PA óptima (PAO); PA normal alta (PANA) e hipertensos estadío I (Hipert.) cuyos IMC fueron: 22,74 + 0,2; 24,4 + 0,48 y 25,06 + 0,66 Kg/m2 respectivamente (P<0,05 de Hipert. y PANA respecto a PAO; los grupos PANA e Hipert. no difirieron significativamente entre sí). Se seleccionaron muestras de estos grupos para el estudio comparativo de: índice cardíaco (IC); resistencia periférica total (RP), glucemia, insulinemia e índice glucosa/insulina y pH intracelular plaquetario. No encontramos diferencias estadísticamente significativas entre los tres grupos examinados en lo que respecta a glucemia, insulinemia e índice glucosa/insulina. Los diferentes niveles de PA de los grupos pueden atribuirse a distintos IC: PAO 3,25 + 0,13; PANA 3,76 + 0,2; Hipert. 4,76 + 0,36 ml/min/m2 (P<0,05). Las RP fueron numéricamente "normales": PAO:2139 + 106; PANA 2170+ 114; Hipert.: 1858 + 146 dinas seg. cm-5 m2 (NS). El pH intracelular plaquetario fue de 7,15 + 0,07 en los PAO, 7,21 + 0,05 en los PANA y 7,33 + 0,04 en los Hipert. (P<0,05 de Hipert. respecto a PAO). El aumento de pH, en el grupo Hipert., sugiere un intercambiador Na+/H+ hiperactivo.

Niveles de presion arterial en jóvenes estudiantes: correlacion con la masa corporal, factores metabólicos y hemodinámicos / Blood pressure levels in young students: correlation between body mass, metabolic and hemodynamic factors

En un grupo homogéneo de 450 estudiantes (20,8 + 0,11 años) se examinaron los niveles de presión arterial (PA) y se correlacionaron con diferentes parámetros. La prevalencia de hipertensión arterial fue, según el criterio del JNC-V, 13 por ciento en varones y 3 por ciento en mujeres. Las correlaciones entre índice de masa corporal (IMC) y niveles de PA fueron estadísticamente significativas en varones y mujeres. La presión arterial media (PAM) aumentó a razón de 1.17 mmHg por cada unidad de incremento en el IMC en los varones y 0.97 mmHg en las mujeres. En base a los niveles de PA propuestos por el JNC-V se seleccionaron tres grupos: varones con PA óptima (PAO); PA normal alta (PANA) e hipertensos estadío I (Hipert.) cuyos IMC fueron: 22,74 + 0,2; 24,4 + 0,48 y 25,06 + 0,66 Kg/m2 respectivamente (P<0,05 de Hipert. y PANA respecto a PAO; los grupos PANA e Hipert. no difirieron significativamente entre sí). Se seleccionaron muestras de estos grupos para el estudio comparativo de: índice cardíaco (IC); resistencia periférica total (RP), glucemia, insulinemia e índice glucosa/insulina y pH intracelular plaquetario. No encontramos diferencias estadísticamente significativas entre los tres grupos examinados en lo que respecta a glucemia, insulinemia e índice glucosa/insulina. Los diferentes niveles de PA de los grupos pueden atribuirse a distintos IC: PAO 3,25 + 0,13; PANA 3,76 + 0,2; Hipert. 4,76 + 0,36 ml/min/m2 (P<0,05). Las RP fueron numéricamente "normales": PAO:2139 + 106; PANA 2170+ 114; Hipert.: 1858 + 146 dinas seg. cm-5 m2 (NS). El pH intracelular plaquetario fue de 7,15 + 0,07 en los PAO, 7,21 + 0,05 en los PANA y 7,33 + 0,04 en los Hipert. (P<0,05 de Hipert. respecto a PAO). El aumento de pH, en el grupo Hipert., sugiere un intercambiador Na+/H+ hiperactivo. (AU)

Chronotropic and inotropic responses to ASL-7022 on isolated rat atria

El compuesto ASL-7022 es una nueva catecolamina sintética con actividad estimulante de los receptores alfa y beta, que ha demostrado una notable selectividad inotrópica "in vivo". En la aurícula aislada de rata, el ASL-7022 produce aumentos en la frecuencia del marcapaso sinusal, la tensión desarrollada y al velocidad de contracción. Los máximos alcanzados en la respuesta ino y cronotrópica son similares a los obtenidos con isoproterenol, a pesar de que su potencia es 676 veces menor. Las respuestas crono e inotrópica son sensibles al bloqueo con propranolol pero no al tratamiento con prazosin. Cuando se analizó la selectividad sobre una repuesta, se encontró que para cualquier concentación considerado el ASL-7022 produce mayor efecto cronotrópico que inotrópico en forma comparable a lo que ocurre con un agonista beta adrenérgico típico, el isoproterenol. Estos resultados indican que le ASL-7022 no presenta selectividad en la aurículo aislada para el efecto inotrópico

Chronotropic and inotropic responses to ASL-7022 on isolated rat atria

El compuesto ASL-7022 es una nueva catecolamina sintética con actividad estimulante de los receptores alfa y beta, que ha demostrado una notable selectividad inotrópica "in vivo". En la aurícula aislada de rata, el ASL-7022 produce aumentos en la frecuencia del marcapaso sinusal, la tensión desarrollada y al velocidad de contracción. Los máximos alcanzados en la respuesta ino y cronotrópica son similares a los obtenidos con isoproterenol, a pesar de que su potencia es 676 veces menor. Las respuestas crono e inotrópica son sensibles al bloqueo con propranolol pero no al tratamiento con prazosin. Cuando se analizó la selectividad sobre una repuesta, se encontró que para cualquier concentación considerado el ASL-7022 produce mayor efecto cronotrópico que inotrópico en forma comparable a lo que ocurre con un agonista beta adrenérgico típico, el isoproterenol. Estos resultados indican que le ASL-7022 no presenta selectividad en la aurículo aislada para el efecto inotrópico (AU)