Evaluation of apoptosis indexes in currently used oral alpha-blockers in prostate: a pilot study

ABSTRACT Objectives: Apoptosis effect of oral alpha-blockers is known in the prostate. Apoptosis index of silodosin has not been proved, yet. Aims are to present apoptosis index of silodosin in prostate and to compare this with other currently used alpha-blocker's apoptosis indexes together with their clinical effects. Materials and Methods: Benign prostatic hyperplasia (BPH) patients were enrolled among those admitted to urology outpatient clinic between June 2014 and June 2015. Study groups were created according to randomly prescribed oral alpha-blocker drugs as silodosin 8mg (Group 1; n=24), tamsulosin 0.4mg (Group 2; n=30), alfuzosin 10mg (Group 3; n=25), doxazosin 8mg (Group 4; n=22), terazosin 5mg (Group 5; n=15). Pa- tients who refused to use any alpha-blocker drug were included into Group 6 as control group (n=16). We investigated apoptosis indexes of the drugs in prostatic tissues that were taken from patient's surgery (transurethral resection of prostate) and/or prostate biopsies. Immunochemical dyeing, light microscope, and Image Processing and Analy- sis in Java were used for evaluations. Statistical significant p was p<0.05. Results: There were 132 patients with mean follow-up of 4.2±2.1 months. Pathologist researched randomly selected 10 areas in each microscope set. Group 1 showed statisti- cal significant difference apoptosis index in immunochemical TUNEL dyeing and im- age software (p<0.001). Moreover, we determined superior significant development in parameters as uroflowmetry, quality of life scores, and international prostate symptom score in Group 1. Conclusions: Silodosin has higher apoptosis effect than other alpha-blockers in prostate. Thus, clinic improvement with silodosin was proved by histologic studies. Besides, static factor of BPH may be overcome with creating apoptosis.

Participation of hepatic α/β-adrenoceptors and AT1 receptors in glucose release and portal hypertensive response induced by adrenaline or angiotensin II

It has been previously demonstrated that the hemodynamic effect induced by angiotensin II (AII) in the liver was completely abolished by losartan while glucose release was partially affected by losartan. Angiotensin II type 1 (AT1) and adrenergic (∝1- and β-) receptors (AR) belong to the G-proteins superfamily, which signaling promote glycogen breakdown and glucose release. Interactive relationship between AR and AT1-R was shown after blockade of these receptors with specific antagonists. The isolated perfused rat liver was used to study hemodynamic and metabolic responses induced by AII and adrenaline (Adr) in the presence of AT1 (losartan) and ∝1-AR and β-AR antagonists (prazosin and propranolol). All antagonists diminished the hemodynamic response induced by Adr. Losartan abolished hemodynamic response induced by AII, and AR antagonists had no effect when used alone. When combined, the antagonists caused a decrease in the hemodynamic response. The metabolic response induced by Adr was mainly mediated by ∝1-AR. A significant decrease in the hemodynamic response induced by Adr caused by losartan confirmed the participation of AT1-R. The metabolic response induced by AII was impaired by propranolol, indicating the participation of β-AR. When both ARs were blocked, the hemodynamic and metabolic responses were impaired in a cumulative effect. These results suggested that both ARs might be responsible for AII effects. This possible cross-talk between β-AR and AT1-R signaling in the hepatocytes has yet to be investigated and should be considered in the design of specific drugs.

Neural Mechanisms and Delayed Gastric Emptying of Liquid Induced Through Acute Myocardial Infarction in Rats / Mecanismos Neurais e Retardo do Esvaziamento Gástrico de Liquido Induzido no Infarto Agudo do Miocárdio em Ratos

Background: In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Objective: Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Methods: Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. Results: No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Conclusion: Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN. .

Fundamento: Distúrbios da motilidade do intestino proximal no infarto agudo do miocárdio podem desencadear sintomas digestivos como náuseas e vômitos. O infarto do miocárdio ocasiona retardo do esvaziamento gástrico (EG) de líquido em ratos. Objetivo: Investigar se existe a influência do nervo vago (VGX), adrenoreceptores α-1, receptores GABAB do sistema nervoso central e participação do núcleo paraventricular (NPV) do hipotálamo no esvaziamento gástrico (EG) e complacência gástrica (CG) em ratos infartados. Métodos: Ratos Wistar (n = 8-15) foram divididos em: grupo infarto (INF), sham (SH) e subdivididos. O infarto foi realizado por ligadura da artéria coronária descendente anterior. A complacência gástrica foi estimada com curvas pressão-volume. Realizada vagotomia por secção dos ramos dorsal e ventral. Para verificar a ação dos receptores GABAB foi injetado baclofeno por via intra ventrículo-cerebral. Simpatectomia química foi realizada com prazosina intravenosa (iv), e na lesão do núcleo paraventricular do hipotálamo foi utilizada corrente elétrica de 1mA/10s, com esvaziamento gástrico determinado por medição da retenção gástrica (% RG) de uma refeição salina. Resultados: Não houve diferença significativa na CG. A vagotomia (VGX) reduziu significativamente a %RG; no grupo INF, o tratamento intra ventrículo-cerebral (ivc) com baclofeno reduziu significativamente a % RG; não houve conclusivamente envolvimento dos receptores GABAB em retardar o EG; o tratamento intravenoso com prazosina reduziu significativamente a %RG no grupo INF. A lesão do NPV aboliu o efeito do infarto do miocárdio no EG. Conclusão: O nervo vago, receptores α-adrenérgicos e núcleo paraventricular estão envolvidos no retardo do esvaziamento gástrico no infarto agudo do miocárdio em ratos. .

Effect of Withania somnifera on forced swimming test induced immobility in mice and its interaction with various drugs.

The objective of the present study was to evaluate the antidepressant action of Withania somnifera (WS) as well as its interaction with the conventional antidepressant drugs and to delineate the possible mechanism of its antidepressant action using forced swimming model in mice. Effect of different doses of WS, fluoxetine and imipramine were studied on forced swimming test induced mean immobility time (MIT). Moreover effect of WS 100 mg/kg, i.p. was observed at different time intervals. Effect produced by combination of sub therapeutic doses of WS with imipramine (2.5 mg/kg, i.p.) as well as fluoxetine (2.5 mg/kg, i.p.) were also observed. Effect of WS (100 mg/kg, i.p.) as well as combination of WS (37.5 mg/kg, i.p.) with either imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.) were observed in mice pretreated with reserpine (2 mg/kg, i.p.) and clonidine (0.15 mg/kg, i.p.). Effects of prazosin (3 mg/kg, i.p.) or haloperidol (0.1 mg/kg, i.p.) pre-treatment were also observed on WS induced decrease in MIT. WS produced dose dependent decrease in MIT. Maximum effect in MIT was observed after 30 min of treatment with WS 100 mg/kg, i.p. Combination of WS (37.5 mg/kg, i.p.) with imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.) also produced significant decrease in the MIT. Clonidine and reserpine induced increase in MIT, was significantly reversed by treatment with WS (100 mg/kg, i.p.) as well as combination of WS (37.5 mg/kg, i.p.) with either imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.). Pre-treatment with prazosin but not haloperidol, significantly antagonized the WS (100 mg/kg, i.p.) induced decrease in MIT. It is concluded that, WS produced significant decrease in MIT in mice which could be mediated partly through a adrenoceptor as well as alteration in the level of central biogenic amines.

Prazosin blocks the glutamatergic effects of N-methyl-D-aspartic acid on lordosis behavior and luteinizing hormone secretion in the estrogen-primed female rat

We have observed that intracerebroventricular (icv) injection of selective N-methyl-D-aspartic acid (NMDA)-type glutamatergic receptor antagonists inhibits lordosis in ovariectomized (OVX), estrogen-primed rats receiving progesterone or luteinizing hormone-releasing hormone (LHRH). When NMDA was injected into OVX estrogen-primed rats, it induced a significant increase in lordosis. The interaction between LHRH and glutamate was previously explored by us and another groups. The noradrenergic systems have a functional role in the regulation of LHRH release. The purpose of the present study was to explore the interaction between glutamatergic and noradrenergic transmission. The action of prazosin, an alpha1- and alpha2b-noradrenergic antagonist, was studied here by injecting it icv (1.75 and 3.5 µg/6 µL) prior to NMDA administration (1 µg/2 µL) in OVX estrogen-primed Sprague-Dawley rats (240-270 g). Rats manually restrained were injected over a period of 2 min, and tested 1.5 h later. The enhancing effect induced by NMDA on the lordosis/mount ratio at high doses (67.06 ± 3.28, N = 28) when compared to saline controls (6 and 2 µL, 16.59 ± 3.20, N = 27) was abolished by prazosin administration (17.04 ± 5.52, N = 17, and 9.33 ± 3.21, N = 20, P < 0.001 for both doses). Plasma LH levels decreased significantly only with the higher dose of prazosin (1.99 ± 0.24 ng/mL, N = 18, compared to saline-NMDA effect, 5.96 ± 2.01 ng/mL, N = 13, P < 0.05). Behavioral effects seem to be more sensitive to the alpha-blockade than hormonal effects. These findings strongly suggest that the facilitatory effects of NMDA on both lordosis and LH secretion in this model are mediated by alpha-noradrenergic transmission.

CNS alpha 1 receptor in tonic pain during estrous cycle in rats.

Estrogen and progesterone are known to affect nociception. The plasma concentrations of these hormones vary during estrous cycle in rodents. The aim of the present study was to investigate the effect of evidence of alpha1 receptor agonist and antagonist on tonic pain in all phases of estrous cycle in female rats. Phenylephrine (alpha1 agonist) and prazosin (alpha1 antagonist) were administered via intracerebroventicular (ICV) injection. Adult female rats weighting 200-220 g were maintained on 12 h light/dark cycle for 10-14 days prior to the experiment. Food and water were made available ad libitum. Formalin test was performed in all phases of estrous cycle. Results showed that phenylephrine caused significant (P<0.05) reduction in pain sensitivity. This reduction was more pronounced during proestrus phase. Prazosin significantly (P<0.05) increased pain sensitivity, particularly during metestrus phase. It is possible that fluctuation in pain sensitivity during estrous cycle is related to the level of sex hormones during estrous cycle.

Comparison of skin permeability of drugs in mice and human cadaver skin.

In vitro percutaneous absorption of four antihypertensive drugs were carried out across the mice and human cavader skin in order to compare their skin permeability. An interesting trend was noticed in these experiments. Poorly water soluble drug prazosin hydrochloride showed 13 times enhanced flux in the mice skin whereas the steady-state flux of the water soluble drug propranolol hydrochloride was almost same in both human cadaver and mice skin. The permeation rate of prazosin hydrochloride and propranolol hydrochloride through the human cadaver skin fluctuated widely over time, but in mice skin, distinct trends were noticed. The study indicates that the overall permeation rate in mice skin is higher than that in the cadaver skin and the meeting of the target-flux in mice skin does not guarantee its good permeability in human skin.

Influence of moderate cooling (37§C-25§C) on the reactivity of isolated rat tail artery

The aim of the investigation was to examine the effects of cooling on the tail artery regarding the scarceness of such studies in spite of the essential thermoregulatory role played by this vessel. Segments of the proximal portion were suspended isometrically in medium containig 1.25 mM Ca. Lowering the temperature to 25 degrees Celsius increased the sensitivity and maximum strength of the adrenaline concentration-effect curves. These changes were reversed by warming to 37 degrees Celsius. Cocaine attenuated the increase of sensitivity without changing the increase of the maximum response. Either the sensitivity and strength of the responses to phenylephrine and serotomin were increased by cooling. Clonidine evoked weak contractions in 18 out of 38 experiments. After cooling, the responses persisted only in 7 arteries and the strength was almost halved. Responses to field eletric stimulation at 25 degrees Celsius exhibited a pronounced increase of strength and a small increase of sensitivity. -log Kb for prazosin against adrenaline was encreased by cooling (8.7 and 9.1 at 37 degrees Celsius and 25 degrees Celsius C, P<0.01). After partial receptor inactivation using phenoxybenzamine, the dissociation-constant (KA) indicated a moderate affinity for phenylephrine that was not changed by cooling (4.1 and 4.2 x 10(-6) at 37 degrees Celsius respectively). Receptor reserve and occupancy at EC(50) also remained unchanged at 25 degrees Celsius. It can be concluded that: 1) cooling increases the tail artery reactivity, partly as a consequence of the inhibition of adrenergic neuronal uptake; 2) responsiveness to alpha 2-agonists is not in volved in the effects of cooling whereas the role of alpha 1-adrenoceptor could not be properly clarified; 3) cooling may facilitate some steps of the contractile activation beyond the agonist-receptor interaction.

Comparison of relaxation responses of cavernous and trigonal smooth muscles from rabbits by alpha1-adrenoceptor antagonists; prazosin, terazosin, doxazosin, and tamsulosin

Alpha1a-adrenergic receptor (AR) primarily mediates the contraction of the prostatic and cavernous smooth muscles. Among clinically available alpha1-AR antagonists for the medical management of benign prostatic hyperplasia (BPH), tamsulosin has a modest selectivity for alpha1A- and alpha1D- over alpha1B-ARs. To compare the effects of various alpha1-AR antagonists on relaxation responses of cavernous and trigonal smooth muscles, isometric tension studies with relatively selective (tamsulosin) and non-selective (prazosin, doxazosin, and terazosin) alpha1A-AR antagonists, were conducted in the cavernous and trigonal muscle strips of rabbits (n=10 each). Tamsulosin had the strongest inhibitory effect on contraction of trigonal smooth muscle among the various alpha1-AR antagonists, and the inhibitory activities of prazosin, doxazosin, and terazosin were not statistically different. All alpha1-AR antagonists caused concentration-dependent relaxation of the cavernous muscle strips. Tamsulosin was shown to have greater potency than prazosin (more than 100-fold), doxazosin (more than 1000-fold), and terazosin (more than 1000-fold), in relaxation of cavernous smooth muscle. In conclusion, tamsulosin might be the most effective drug among the four commonly used alpha1-AR antagonists for the medical management of BPH. Tamsulosin might be a potential substitute for phentolamine in combination with vasoactive agents as an intracavernous injection therapy for patients with erectile dysfunction.

Interaction between NO and oxytocin: influence on LHRH release

Nitric oxide synthase (NOS)-containing neurons have been localized in various parts of the CNS. These neurons occur in the hypothalamus, mostly in the paraventricular and supraoptic nuclei and their axons project to the neural lobe of the pituitary gland. We have found that nitric oxide (NO) controls luteinizing hormone-releasing hormone (LHRH) release from the hypothalamus acting as a signal transducer in norepinephrine (NE)-induced LHRH release. LHRH not only releases LH from the pituitary but also induces sexual behavior.On the other hand, it is known that oxytocin also stimulates mating behavior and there is some evidence that oxytocin can increase NE release. Therefore, it occurred to us that oxytocin may also stimulate LHRH releave via NE and NO. To test this hypothesis, we incubated medial basal hypothalamic (MBH) explants from adult male rats in vitro. Following a preincubation period of 30 min, MBH fragments were incubated in Krebs-Ringer bicarbonate buffer in the presence of various concentrations of oxytocin. Oxytocin relesed LHRH at concentrations ranging from 0.1 nM to 1muM with a maximal stimulatory effect (P<0.001) at 0.1 muM, but with no stimulatory effect at 10 muM. That these effects were mediated by NO was shown by the fact that incubation of the tissues with NG-monomethyl-L-arginine (NMMA), a competitive inhibitor of NOS, blocked the stimulatory effects. Furthermore, the release of LHRH by oxytocin was also blocked by prazocin, an alpha1-adrenergic receptor antagonist, indicating that NE mediated this effect. Oxytocin at the same concentrations also increased the activity of NOS (P<0.01) as measured by the conversion of [14C]arginine to citrulline, which is produced in equimolar amounts with NO by the action of NOS. The release of LHRH induced by oxytocin was also accompanied by a significant (P<0.02) increase in the release of prostaglandin E2 (PGE2), a mediator of LHRH release that is released by NO. On the other hand, incubation of neural lobes with vaious concentrations of sodium nitroprusside (NP) (300 or 600 muM), a releaser of NO, revealed that NO acts to suppres (P<0.01) the release of oxytoxin. Therefore, our results indicate that oxytocin releases LHRH by stimulating NOS via NE, resulting in an increased release of NO, which increases PGE2 release that in turn induces LHRH release. Furthermore, the released NO can act back on oxytocinergic terminals to suppress the release of oxytocin in an ultrashort-loop negative feedback.

Effect of chronic treatment with atenolol and prazosin in streptozotocin induced diabetic rats.

Diabetes-mellitus was induced in rats by single intravenous injection of (45 mg/kg) streptozotocin (STZ). STZ diabetic rats showed hypertension, decreased cardiac functions, cardiomyopathy and hypercholesterolemia observed at the end of six weeks. Chronic treatment with atenolol (10 mg/kg) for six weeks in the diabetic rats reduced the elevated blood pressure, but failed to prevent STZ induced other complications. Chronic treatment with prazosin (1 mg/kg, po) in the diabetic rats, reduced the elevated blood pressure and also partially prevented hypercholesterolemia, cardiac dysfunctions and in particular the cardiomyopathy. The results suggest that prazosin may be a better option as compared to atenolol in hypertension when it is associated with diabetes mellitus.

Prazosin and stress effect on tumoral growth of 7.12-Dimethylbenz[A]anthracene-induced rat mammary tumors

Repeated isolation stress and prazosin effect were evaluated in 7,12-dimetylbenz [A] anthracene (DMBA) mammary tumors. Tumor volume was significantly lower in stressed than in control animals from 10 to 52 days considering day 1 the moment when tumors became palpable and treament began. Control Prazosin (0.5 mg/Kg) rats showed diminished tumor volume after 40 days. Stress Prazosin curve was similar to stress alone. The proportion of progressing tumors in control was significantly higher than in stressed groups, regardless of Prazosin administration. Body weight gain was similar in every group throughout the experiment. Behavioral studies were performed when stress effect was no longer evident. Grooming and the number of fecal boli were similar in all groups, as well as prolactin serum levels, suggesting that habituation took place. No significant differences were observed between groups for estrogen receptors. However, a greater concentration of progesterone receptors was found in Stressed rats, compared to all other groups. We conclude that the decrease of tumor volume provoked by stress could not be reversed by the alpha 1-adrenergic antagonist prazosin. Then, it appears that the main effect of stress is not mediated by the alpha 1-adrenergic receptors. Higher progesterone receptors in stressed rats could explain the differences observed.

Alpha-adrenergic pathways in the lateral hypothalamus are important for the dipsogenic effect of carbachol injected into the medial septal area

We studied the effect of the Ó1-and Ó2-adrenergic receptors of the lateral hypothalamus (LH) on the control of water intake induced by injection of carbachol into the medial septal area (MSA) of adult male Holtzman rats (250-300g) implanted with chronic stainless steel cannulae into the LH and MSA. The volume of injection was always 1 µl and was injected over a period of 30-60 s. For control, 0.15MNaCl was used. Clonidine (20 nmol) but not phenylephrine (160 nmol) injected into the LH inhibited water intake induced by injection of carbachol (2 nmol) into the MSA, from 5.4 ñ 1.2ml/h to 0.3 ñ 0.1 and 3.0 ñ 0.9 ml/h, respectively (N=26). When we injected yohimbine (80nmol) + clonidine (20nmol) and prazosin (40nmol) + clonidine (20nmol) into the LH, water intake induced by injection of carbachol into the MSA was inhibited from 5.4 ñ 1.2 ml/h to 0.8 ñ 0.5 and 0.3 ñ 0.2 ml/h, respectively (N=19). Water intake induced by carbachol (2nmol) injected into the MSA was decreased by previous injection of yohimbine (80 nmol) + phenylephrine (160 nmol) and prazosin (40 nmol) + phenylephrine (160 nmol) from 5.4 ñ 1.2ml/h to 1.0 ñ 0.7 and 1.8 ml/h, respectively (N = 16). The cannula reached both the medial septal area in its medial portion and the lateral hypothalamus. It has been suggested that the different pathways for induction of drinking converge on a final common pathway. Thus, adrenergic stimulation of Ó2-adrenoceptors of LH can influence this final common pathway

On the characterization of dopamine-induced contractile response of rat anococcygeus muscle preparation.

Presence of specific dopamine (DA) receptors and their characterization was attempted in rat anococcygeus muscle preparation. Dopamine (10(-6) M) and B-HT 920 (10(-6) M) produced concentration dependent contractions of the rat anococcygeus muscle preparation. The response of DA was shifted towards right in presence of haloperidol (10(-6) M; pA2 = 6.8) and sulpiride (10(-4) M) in a competitive manner. Alpha 2 antagonists yohimbine (10(-5) M) and idazoxan (10(-5) M) blocked the response to DA in a competitive manner, while alpha 1 antagonist prazosin (10(-5) M) completely blocked the response to DA. SCH 23390 (10(-5) M), a D1 DA antagonist potentiated the response to DA. Reserpinization (5 mg/kg, 24 hr prior) brought about a shift towards the right, and this response was similarly blocked by haloperidol, sulpiride and yohimbine without affecting the maximum response. Desipramine (10(-5) M) blocked the response of DA in a non-competitive manner. Pretreatment of animals with desipramine (10 mg/kg) followed by reserpine, brought about a reversal of action of reserpine. The response to B-HT 920 (10(-6) M), was blocked similarly by haloperidol and yohimbine. However, the effect of desipramine was more pronounced when compared to DA per se. SKF 38393, a D1 DA agonist, potentiated the response to B-HT 920. The findings suggest the presence of both D1 and D2 DA receptors in rat anococcygeus muscle and that DA also acts on adrenergic receptors to produce a contractile response of this muscle preparation.

Influence of sympathetic tone on the reactivity to indorenate in the external carotid vascular bed of the dog

The present study was designed to analyze the effects of drugs th at interfere with sympathetic transmission on the external carotid vasodilator response induced by the 5-HT1A receptor agonist, indorenate, in pentobarbital-anesthetized dogs. Intracarotid (i.c.) infusions of indorenate (1000 µg/lmin) produced an increase in external carotid blood flow (external C.B.F.) without modifying mean arterial blood pressure or heart rate. This effect of indorenate was dose-dependently antagonized by intravenous (i.v.) administration of the Ó1-adrenoceptor antagonist, prazosin (1, 3.1, 10, 31 and 100 µg/kg), the ganglionic blocking agent, mecamylamine (0.31, 0.1, 0.31, 1, 3.1 and 10 mg/kg) or the 5-HT2 receptor and Ó1-adrenoceptor antagonist, ketanserin (10, 31 and 100 µ/kg). It is concluded that indorenate.induced increase in canine external C.B.F. is dependent on the vascular neurogenic tone

Eritrocitosis secundaria a hipoxia hipobárica bloqueo farmacológico / Secondary erythrocites to hypobaric anoxia: a pharmacological block

Con el objetivo de evaluar la eficacia del prazosín intraperitoneal (400ug/kg/día) en el bloqueo de la eritropoyesis secundaria se realizaron las siguientes pruebas: determinación de hematocrito, consumo de oxigeno e incorporación de Fe, en ratones albinos machos de las cepas swiss. Además se hizo la determinación del hematocrito en ratones sometidos a las mismas condiciones de hipoxia y tratados con propanolol (95mg/kg/día), enalapril (2,8mg/kg/día), teofilina (320mg/kg/día) y pentoxifilina (1,43g/kg/día), todos por vía oral. Se consideraron dos grupos tratados: un grupo preventivo (gp) y un grupo terapéutico (gt). Al gp se le administró el fármaco desde el primer día de la exposición a hipobáricos, mientras que el gt se le sometió a hipobárico durante 4-6 semanas y una vez incrementado el hematocrito recibieron tratamiento durante 3-6 semanas, se obsevó en los tratados una respuesta eritropoyética significativamente menor. El análisis de varianza de dos vías revela un significativo efecto del prazosín y del tiempo de tratamiento.

Aggravating action of hydralazine on ethanol-induced gastric lesions.

Endogenous nitric oxide has been proposed as one of the mediators of gastric cytoprotection. We studied the effect of the vasodilator hydralazine which acts via nitric oxide and thus is expected to have a gastroprotective action. However, hydralazine aggravates ethanol-induced gastric lesions. This effect is not influenced by pretreatment with the selective alpha 1 adrenergic antagonist prazosin but is abolished by the angiotensin converting enzyme inhibitor, captopril suggesting the involvement of the renin-angiotensin system.

Tratamiento médico de la hiperplastía benigna de próstata con alfa bloqueadores / Medical treatment of benign prostatic hyperplasia with alpha blockaders

Presentamos el efecto de los alfa bloqueadores en el tratamiento de la hiperplasia benignas de próstata en 11 pacientes ambulatorios en el HNGAI. En el 100 por ciento de los casos, presentaron mejoría tanto objetiva como subjetiva, con controles flujométricos que demuestran incremento en el flujo máximo, así como una disminución en el residuo vesical y en la frecuencia urinaria, tanto diurna como nocturna. Presentamos un seguimiento corto debido a deficiencias en la obtención del producto. Creemos que las indicaciones médicas para su uso son limitadas a obtener una mejor espera para la cirugía o en los casos que no esté indicada la intervención. Es el primer reporte que se realiza en nuestro medio

Influência dos adrenoceptores alfa1 e alfa2 do hipotálamo médio sobre a pressao arterial sistêmica em ratos / Role of the alfa1 and alfa2 adrenoceptores in the medial hypothalamus on the arterial pressure in rats

Foram estudados os efeitos sobre a pressäo arterial sistêmica após a administraçäo de noradrenalina e de dois antagonistas de alfa-adrenoceptores no hipotálamo médio de ratos normotensos. Tanto o prazosin quanto a ioimbina antagonizaram a açäo do agonista misto de alfa1/alfa2-adrenoceptores, a noradrenalina ; entretanto a administraçäo prévia de prazosin mostrou uma maior interaçäo da noradrenalina pelos adrenoceptores alfa1. Estes resultados sugerem que os adrenoceptores alfa1 do hipotálamo médio exerceriam uma maior influência que os adrenoceptores alfa2 no controle de pressäo arterial sistêmica