Lead acetate induced contraction in rat tracheal smooth muscle is independent of epithelium.

Airways are the primary target of lead exposure from atmospheric pollution, its effect on airway smooth muscle and their responsiveness to bronchoactive agents is not clearly understood. In the present investigation the effect of lead on the isolated airway smooth muscle activity was studied in organ bath set-up. Further the involvement of airway epithelium was examined and the responsiveness of airway smooth muscle to adenosine, acetylcholine (bronchoconstrictors) and isoproterenol (bronchodilator) was also investigated. Lead in concentration of 10(-12) M to 10(-4) M produced concentration-dependant contractile response in rat tracheal rings. Acetylcholine and adenosine induced concentration-dependent contractile response was slightly inhibited after lead exposure. The relaxant response to isoproterenol was also inhibited in lead exposed tissues. Epithelium removal did not significantly change the contractile response to lead suggesting that the lead induced contraction of airway smooth muscle is epithelium independent.

Valor del test de dobutamina comparado con la ergometria en la evaluacion de riesgo coronario / Comparison between electrocardiographic test with dobutamine and exercise stress testing on coronary risk stratification

La ergometría es el método de elección para estratificar el riesgo de eventos luego de un infarto agudo de miocardio, pero el 20-40% de la población no puede realizarla. La utilización de dobutamina con control electrocardiográfico es una propuesta segura, fácil de realizar y reproducible. Nuestro objetivo fue evaluar la utilidad de dicho test para predecir los resultados de la ergometría en pacientes (49 mujeres), edad: 60.5+/- 11.7 años con primer infarto agudo de miocardio no complicado. Se realizó al quinto día del test de dobutamina con control electrocardiográfico y al sexto día la ergometría. Se consideró positiva la presencia de angor y/o infradesnivel del segmento ST mayor ou igual 1mV en ambas pruebas. Se determinó sensibilidad, especificidad, valor predictivo positivo y negativo del test de dobutamina, test de concordancia y valor kappa, con p>0.05. El test de dobutamina fue positivo en 91 casos. La ergometría fue positiva en 54 pacientes. No hubo diferencias hwemodinámicas entre ambos métodos. Cuarenta y nueve presentaron ambas pruebas positivas sin diferencias en las variables analizadas; 114 pacientes ambas negativas, en los que durante la ergometría se alcanzó mayor presión arterial y doble producto máximo. En 47 los resultados fueron discorfdantes. El test dobutamina predijo los resultados de la ergometría con sensibilidad: 90.7% (IC95%:78.9-96.5%), especificidad: 73%(IC95%:65.3-79.7%), valor predictivo positivo:54% (IC95%:43.1-62.2%) y negativo: 95.8% (IC95%:89.9-98.4%), concordancia: 77% (IC95%:53-74) y valor kappa:0.52 (IC95%:0.41-0.63). El test de dobutamina predijo los resultados de la ergometría con adecuadas sensibilidad, especificidad y valor predictivo positivo; se destaca el alto valor predictivo negativo del método que resultó un procedimiento seguro, eficaz y sencillo.

Do Acute Changes in Heart Rate by Isoproterenol Affect Aortic Stiffness in Patients with Hypertension?

BACKGROUND: Increased aortic stiffness is a independent risk factor of cardiovascular disease in patients with hypertension. Acute changes of the heart rate (HR) have been reported not to affect the aortic stiffness in pacing. However, it is unknown whether acute changes in HR caused by sympathomimetics can affect the aortic stiffness in patients with hypertension. We investigated the effect of acute changes in HR produced by isoproterenol on the aortic stiffness in 17 hypertensive patientss (mean age: 59 +/- 9 years). METHODS: All vasoactive drugs were discontinued at least 3 days before the study. The carotid-tofemoral pulse wave velocity (PWV) was measured by the foot-to-foot method. The pulse waves were recorded at the baseline and at every increase of HR by 5 to 10 bpm with a gradual increase of the dose of isoproterenol. The blood pressures and HR were measured simultaneously. For the analysis, HR, PWV, compliance (C), and compliance index (Ci) were converted as percent changes (delta) from the baseline values. Percent changes of the parameters of the aortic stiffness, i.e., delta PWV, delta C, and delta Ci, were grouped by every 10% increase in delta HR. RESULTS: There was no significant difference among groups in delta PWV, delta C and delta Ci (p> 0.05 for each of the group). The regression analysis showed no significant correlation of delta HR with delta PWV and delta C (r=0.18, 0.13 respectively, p> 0.05 for each). delta Ci had a poor correlation with delta HR (r=0.22, p< 0.05). However, only 4.6% of delta Ci could be referred to delta HR (r2=0.046). CONCLUSION: Aortic stiffness was not affected by acute changes in HR produced by isoproterenol which suggests that it is not necessary to consider acute changes in HR when measuring aortic PWV.

Ibopamina tópica na propedêutica do glaucoma / Ibopamine provocative test in glaucoma

Objetivo: Avaliar o efeito da ibopamina a 2 por cento (agonista dopaminérgico), em forma de colírio, sobre a pressão intra-ocular (Po), em olhos com glaucoma primário de ângulo aberto (GPAA) e em olhos normais. Local: Departamento de Glaucoma do Centro de Referência em Oftalmologia do Hospital das Clínicas da Universidade Federal de Goiás e Departamento de Glaucoma do Centro Brasileiro de Cirurgia de Olhos - CBCO - Goiânia - GO. Método: Foram selecionados 30 pacientes (60 olhos) com GPAA e 30 pacientes (60 olhos) normais e submetidos ao teste provocativo com ibopamina a 2 por cento. O teste foi considerado positivo quando, 45 minutos após a instilação de 2 gotas de colírio de ibopamina a 2 por cento, com o intervalo de 5 minutos entre as gotas, houve aumento da Po > ou = 4mmHg. A Po foi também aferida em todos os olhos 45 minutos após a instilação de 2 gotas de fenilefrina a 10 por cento. Resultados: O teste da ibopamina foi positivo em 53 (88 por cento) olhos com GPAA e em 4 (6,6 por cento) dos olhos normais e não houve aumento significativo da Po em nenhum grupo após a instilação de fenilefrina a 10 por cento. Conclusão: Os resultados deste estudo preliminar sugerem que a ibopamina em forma de colírio pode representar uma alternativa na avaliação do equilíbrio hidrodinâmico intra-ocular em olhos com glaucoma.

Fluid and amylase secretion by perfused parotid gland: physio-morphological approach

Whole gland perfusion technique was applied to rat parotid glands to assess whether amylase affects fluid secretion. Control perfusion without any secretagogue evoked no spontaneous secretion. Carbachol (CCh 1 microM) induced both amylase and fluid secretion with distinctive kinetics. Fluid secretion occurred constantly around 60 microL/g-min, whereas amylase secretion exhibited an initial peak, followed by a rapid decrease to reach a plateau. Isoproterenol (Isop 1 microM) alone did not induce fluid secretion although it evoked amylase secretion as measured in isolated perfused acini. Addition of Isop during CCh stimulation evoked a rapid and large rise in amylase secretion accompanied by small increase in oxygen consumption. Morphological observations carried out by HR SEM and TEM revealed exocytotic profiles following Isop stimulation. CCh stimulation alone seldom showed exocytotic profiles, suggesting a low incidence of amylase secretion during copious fluid secretion. Combined stimulation of CCh and Isop induced both vacuolation and exocytosis along intercellular canaliculi. These findings suggest that control of salivary fluid secretion is independent of the amylase secretion system induced by CCh and/or Isop.

The serotonin paradox: drug-receptor interaction in rat vas deferens

The contractile effect of serotonin was studied in rat vas deferens, in comparison with that of noradrenaline and tyramine, after reserpine treatment, surgical denervation, and transplantation to the colon. In reserpinized animals the effect of 5HT resembled that of tyramine, since it was strikingly reduced, in spite of a small residual effect, showing that in normal preparations the effects of 5HT and tyramine are predominantly duc to the release of endogenous noradrenaline. However, in denervated or transplanted vas deferens, in which the effect of tyramine is also abolished, the effect of 5HT was potentiated. It is suggested that after chronic, long lasting depletion of endogenous noradrenaline, there are alternate mechanisms that are generated to improve the contractile effect of 5HT, but not of tyramine. The nature of these mechanisms is still unknown.

Eficácia da adrenalina, noradrenalina, angiotensina II e vasopressina na ressuscitaçäo cardiorrespiratória: estudo experimental na fibrilaçäo ventricular prolongada / Efficacy of adrenaline, noradrenaline, angiotensin II and vasopressin in cardiopulmonary resuscitation: experimental study in prolonged ventricular fibrillation

Estudos experimentais e clínicos têm mostrado que uma pressão de perfusão coronariana (PPCor) maior que 20-30 mmHg é fundamental para que haja restauração da circulação espontânea (RCE) durante as manobras de RCR. O principal objetivo do presente estudo foi o de avaliar a eficácia da adrenalina (ADR), noradrenalina (NOR), angiotensina II (AII) e arginina-vasopressina (AVP) na PPCor e na RCE, num modelo camino de RCR da fibrilação ventricular (FV) prolongada (10 min). Métodos. Cinqüenta animais mestiços, ambos os sexos, peso 12,5 + 3,5 Kg, sedados com fetanil/droperidol e anestesiados com tiopental sódico (20 mg/Kg), mantidos em posição supina, foram intubados e ventilados com ar (VC: 20 ml/Kg; FR: 15/min - Harvard-Pump Animal Ventilator). As pressões de aorta torácica e átrio direito e o ECG (DII) foram registrados continuamente (Mingograf-804, Siemens-Elema). A FV foi induzida eletricamente (4V, 500 mA, 60 Hz) através de um cabo de MP posicionado em VD, e a RCR manual (1 ventilação c/ar/5 compressões torácicas externas) foi iniciada 10 minutos depois. Ao final do 2§ min de RCR, os animais, divididos em 5 grupos iguais, receberam, via IV central: Salina (SAL), 10 ml (grupo A); ADR, 0,2 mg/Kg (grupo B); NOR, 0,2 mg/Kg (grupo B); NOR, 0,2 mg/Kg (grupo C); AII, 0,1 mg/Kg (grupo D) e AVP, 0,8 U/Kg (grupo E). As tentativas de desfribrilação foram iniciadas 2 min após a injeção das drogas, com choques espaçados de 15 seg, até a obtenção de um ritmo eletrocardiograficamente viável ou até atingir o máximo de 6 choques liberados.

In vivo effects of a single dose of norepinephrine and epinephrine on tissue respiration of hibernating and non-hibernating species of frogs.

In vivo effects of a single dose of norepinephrine (NE) and epinephrine (EP) were studied on the rate of tissue (liver and skeletal muscle) respiration in Rana limnocharis (hibernating Sp.) and Rana cyanophlyctis (non-hibernating Sp.) during winter and summer months after 10 and 30 min, 1, 6, 12 and 24 hr of administration. During winter both NE and EP induced significant increase in the rate of tissues respiration only after 30 min after their administration in both the species and the stimulatory effect lasted up to 6 hr. During summer, however, NE and EP stimulated respiratory rate of tissues comparatively after a shorter lag period (10 to 30 min) in R. limnocharis than that of R. cyanophlyctis (30 min to 6 hr). These findings seem to suggest that NE and EP can stimulate tissue respiration very quickly, and, therefore, might be suitable as emergency hormones for instant/faster stimulation of energy metabolism in amphibians.

Analgesic and anti-inflammatory screening of two Brazilian medicinal plants: a positive and a false-positive result

Medical plants used in Brazilian folk medicine to treat pain and inflammation constitute 20 per cent of the current publications on plants in the country. The experimental methods to screen these activities, however, are frequently influenced by previous conditions of the animals and other properties of the tested material unrelated to their putative effects. An example is herein reported on studies carried out with two plants reputed for their anti-inflammatory activities: Scoparia dulcis L. collected in Sao Luis, state of Maranhao and Piper marginatum Jacq. collected in Recife, state of Pernambuco. The aerial parts were extracted in hot water, the extracts concentrated and freeze-dried. Previous treatment of rats with either water (0.5 and 1 g/Kg, p.o), decreased the edema produced by carrageenin in the rat paw (40 per cent and 70 per cent), but only the extracts of S. dulcis inhibited the exudate and leukocyte migration induced by carrageenin in the rat pleurisy model (by 60 per cent and 70 per cent, respectively). The ethanolic extract of S. dulcis was more active than the water extract. All extracts reduced the acetic acid induced writhing in mice (by 20 to 60 per cent), the S. dulcis extract being more potent than that of P. marginatum. Both extracts, however, were ineffective in the tail flick test. Intravenous injection of either extract induced hypertension in both anesthetized and unanesthetized rats, but only P. marginatum produced hypertension after oral administration. This effect was blocked after treatment with prazosin (1 mg/Kg). In the isolated rat vas deferens the aqueous and purified extracts induced contractions parallel to those produced by noradrenaline (10(-8) - 10(-4) M) which were blocked by prazosin (10(-7) M). Contractions of electrically paced rat left atria preparations were pontentiated in the presence of either extract (by 30 to 220 per cent), the effect being blocked buy propranolol (2muM). High performance liquid chromatographic analysis of purified hypertensive fractions revealed the presence of both adrenaline and noradrenaline in both extracts. The results indicated that only the S. dulcis extracts presented analgesic/anti-inflammatory effects unrelated to vasoconstriction induced by both catecholamines. The effects obtained upon injection of P. marginatum extracts were unspecific and correlated with the general sympathomimetic effects produced by the extract.

Effect of intracerebroventricular injection of ramipril on the drinking response caused by injection of noradrenaline into the third ventricle

We studied the effect of ramipril injected into the third ventricle (3rdV) on the control of water intake induced by injection of noradrenaline into the 3rdV of adult male Holtzman rats (250-300 g) implanted with a chronic stainless steel cannula into the 3rdV. The injection volume was always 1mul and was injected over a period of 30-60 sec. Control animals were injected with 0.15 M NaCl. After the injection of isotonic saline (control, O.15 M NaCl) into the 3rdV, water ingestion was 0.3 ñ 0.1 ml/h. Ramipril(l mug/mul)injected into the 3rdV prior to isotonic saline produced no changes in water ingestion (0.4 ñ 0.2 ml/h). The injection of noradrenaline (40 nmol/mul) after isotonic saline induced an increase in water intake (3.0 ñ 1.1 ml/h). The prior injection of ramipril decreased this ingestion to 1.8 + 0.3 ml/ h. These data show that the inhibition of converting enzyme in the brain reduces the water intake induced by catecholaminergic stimulation. We conclude that the brain is able to transform the prodrug ramipril into the active drug ramiprilat.

Inotrópicos positivos näo digitálicos / Nondigitalic positive inotropics

O objetivo do presente trabalho é o de revisar a literatura a respeito das indicaçoes dos inotrópicos positivos nao digitálicos nas cardiopatias. Este trabalho ressalta a pesquisa de novas drogas inotrópicas positivas, as quais nao se encontram disponíveis para o uso na clínica cardiológica. Foram estudados, também, dosagens, mecanismos de açao e indicaçoes das referidas drogas.