Passive Cigarette Smoking Impact on Blood Pressure Response to Epinephrine and Felypressin in 1K1C Hypertensive Rats Treated or not with Atenolol / Impacto do Tabagismo Passivo na Resposta Pressórica à Epinefrina e Felipressina em Ratos Hipertensos 1K1C Tratados ou não com Atenolol

Abstract Background: Cigarette smoking is usually associated with hypertension and may modify vasoconstrictor response. Objective: The present study aimed to analyze and compare the interaction of passive cigarette smoking and hypertension on epinephrine and felypressin blood pressure effects after intravascular injection. Method: 45-day male Wistar rats had the main left renal artery partially constricted and the right kidney removed (1K1C model). Rats were placed in the chamber for exposition to passive cigarette smoking (10 cigarettes) during 10 min (6 days a week). Hypertensive rats received atenolol (90 mg/kg/day) by gavage for two weeks. Hypotensive and hypertensive response, response duration and heart rate were recorded from direct blood pressure values. The significance level was 5%. Results: Passive cigarette smoking increased maximal hypertensive response to epinephrine in normotensive and 1K1C-atenolol treated rats and to felypressin only in 1K1C-atenolol treated rats; it also reduced epinephrine hypotensive response. Epinephrine increased heart rate in normotensive and hypertensive passive smokers or non-smoker rats. Comparing the two vasoconstrictors, epinephrine showed greater hypertensive response in normotensive smokers, 1K1C-atenolol treated smokers and non-smokers. However, in normotensive-nonsmoker rats, felypressin showed a greater and longer hypertensive effect. Conclusions: Our results suggest that passive cigarette smoking may reduce epinephrine vasodilation and increase hypertensive response when compared to felypressin. Therefore, felypressin may be safe for hypertensive patients to avoid tachycardia and atenolol interaction, but for normotensive and non-smoker patients, epinephrine may be safer than felypressin.

Resumo Fundamento: O tabagismo geralmente está associado à hipertensão e pode modificar a resposta vasoconstritora. Objetivo: O presente estudo teve como objetivo analisar e comparar a interação do tabagismo passivo e hipertensão sobre os efeitos da epinefrina e felipressina na pressão arterial após injeção intravascular. Métodos: Ratos Wistar machos de 45 dias tiveram a artéria renal principal esquerda parcialmente obstruída e o rim direito removido (modelo 1K1C). Os ratos foram colocados na câmara para exposição ao tabagismo passivo (10 cigarros) durante 10 minutos (6 dias por semana). Ratos hipertensos receberam atenolol (90 mg/kg/dia) por gavagem durante duas semanas. A resposta hipotensora e hipertensiva, a duração da resposta e a frequência cardíaca foram registradas a partir da medida dos valores diretos da pressão arterial. O nível de significância foi de 5%. Resultados: O tabagismo passivo aumentou a resposta hipertensiva máxima à epinefrina em ratos normotensos e ratos 1K1C tratados com atenolol e à felipressina apenas em ratos 1K1C tratados com atenolol; também reduziu a resposta hipotensiva à epinefrina. A epinefrina aumentou a frequência cardíaca em ratos fumantes passivos ou não-fumantes, normotensos e hipertensos. Comparando os dois vasoconstritores, a epinefrina apresentou maior resposta hipertensiva em fumantes normotensos, ratos 1K1C fumantes e não fumantes tratados com atenolol. No entanto, em ratos normotensos e não fumantes, a felipressina apresentou um efeito hipertensivo maior e mais prolongado. Conclusões: Nossos resultados sugerem que o tabagismo passivo pode reduzir a vasodilatação da epinefrina e aumentar a resposta hipertensiva quando comparado à felipressina. Portanto, a felipressina pode ser segura para pacientes hipertensos, com o objetivo de evitar a interação entre taquicardia e atenolol, mas para pacientes normotensos e não-fumantes, a epinefrina pode ser mais segura que a felipressina.

Pharmacological modulation of b-adrenoceptors as a new cardioprotective strategy for therapy of myocardial dysfunction induced by ischemia and reperfusion

Abstract Purpose: To evaluate the cardioprotective response of the pharmacological modulation of β-adrenergic receptors (β-AR) in animal model of cardiac ischemia and reperfusion (CIR), in spontaneously hypertensive (SHR) and normotensive (NWR) rats. Methods: CIR was induced by the occlusion of left anterior descendent coronary artery (10 min) and reperfusion (75 min). The SHR was treated with β-AR antagonist atenolol (AT, 10 mg/kg, IV) 5 min before CIR, and NWR were treated with β-AR agonist isoproterenol (ISO, 0.5 mg/kg, IV) 5 min before CIR. Results: The treatment with AT increased the incidence of VA, AVB and LET in SHR, suggesting that spontaneous cardioprotection in hypertensive animals was abolished by blockade of β-AR. In contrast, the treatment with ISO significantly reduced the incidence of ventricular arrhythmia, atrioventricular blockade and lethality in NWR (30%, 20% and 20%, respectively), suggesting that the activation of β-AR stimulate cardioprotection in normotensive animals. Serum CK-MB were higher in SHR/CIR and NWR/CIR compared to respective SHAM group (not altered by treatment with AT or ISO). Conclusion: The pharmacological modulation of β-AR could be a new cardioprotective strategy for the therapy of myocardial dysfunctions induced by CIR related to cardiac surgery and cardiovascular diseases.

The role of atenolol in the modulation of the expression of genes encoding pro- (caspase-1) and anti- (Bcl2L1) apoptotic proteins in endothelial cells exposed to intestinal ischemia and reperfusion in rats

Abstract Purpose: To investigate the role of atenolol in the gene expression of caspase 1 (Casp1) and Bcl2L1 on vascular endothelium of rat intestine after ischemia and reperfusion (IR). Methods: Eighteen adult male Wistar rats were randomly divided into 3 groups (n=6): SG (Sham group): no clamping of the superior mesenteric artery; IRG: IR plus saline group: IRG+At: IR plus Atenolol group. Rats from IRG and IRG+At were subjected to 60 min of intestinal ischemia and 120 min of reperfusion. Atenolol (2mg/kg) or saline were injected in the femoral vein 5 min before ischemia, 5 min and 55 min after reperfusion. Thereafter, intestinal segments were appropriately removed and processed for Endothelial Cell Biology Rat RT2 Profiler PCR Array. Results: the anti-apoptotic Bcl2L1 gene expression was significantly down-regulated (-1.10) in the IRG and significantly up-regulated in the IRG+At (+14.15). Meanwhile, despite Casp1 gene expression was upregulated in both groups, it was significantly higher in the IRG (+35.06) than the IRG+At (+6.68). Conclusions: Atenolol presents antiapoptotic effects on rat intestine subjected to IR partly by the up-regulation of the anti-apoptotic Bcl2L1 gene expression. Moreover, atenolol can mitigate the pro-apoptotic and pro-inflammatory effects of Casp1 gene on rat intestine after IR.

Effect of atenolol pre-treatment in heart damage in a model of intestinal ischemia-reperfusion

Abstract Purpose: To investigate the effects of atenolol in inflammatory mediator and oxidative stress in a myocardial injury by intestinal ischemia/reperfusion in rat model. Methods: Adult Wistar male rats were randomly (n=8), anesthetized and divided in: Sham: submitted to operation only; group SS+IR: intravenous saline infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); group AT+IR: intravenous atenolol infusion (2 mg/kg) following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); and group AT+I+AT+R: intravenous atenolol infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and in the time 45 minutes other atenolol doses were administrated and the artery was open for 120 minutes (reperfusion), all animals were submitted to muscular relaxation for mechanical ventilation. In the end of experiment the animals were euthanized and the hearts tissue were morphology analyzed by histology and malondialdehyde by ELISA, and the plasma were analyzed for tumor necrosis factor-alpha by ELISA. Results: The group SS+IR demonstrated the higher malondialdehyde levels when compared with the atenolol treated-groups (p=0.001) in the heart tissue. The tumor necrosis factor-alpha level in plasma decrease in the treated groups when compared with SS+IR group (p=0.001). Histology analyses demonstrate pyknosis, edema, cellular vacuolization, presence of inflammatory infiltrate and band contraction in the heart tissue of the rats. Conclusion: Atenolol significantly reduce the degree of cardiac damage after intestinal ischemia-reperfusion.

Effect of selective beta-adrenoceptor blockade and surgical resection of the celiac-superior mesenteric ganglion complex on delayed liquid gastric emptying induced by dipyrone, 4-aminoantipyrine, and antipyrine in rats

There is evidence for participation of peripheral β-adrenoceptors in delayed liquid gastric emptying (GE) induced in rats by dipyrone (Dp), 4-aminoantipyrine (AA), and antipyrine (At). The present study aimed to determine whether β-adrenoceptors are involved in delayed GE induced by phenylpyrazole derivatives and the role of the prevertebral sympathetic nervous system in this condition. Male Wistar rats weighing 220-280 g were used in the study. In the first experiment rats were intravenously pretreated with vehicle (V), atenolol 30 mg/kg (ATE, β1-adrenergic antagonist), or butoxamine 25 mg/kg (BUT, β2-adrenergic antagonist). In the second experiment, rats were pretreated with V or SR59230A 2 mg/kg (SRA, β3-adrenergic antagonist). In the third experiment, rats were subjected to surgical resection of the celiac-superior mesenteric ganglion complex or to sham surgery. The groups were intravenously treated with saline (S), 240 µmol/kg Dp, AA, or At, 15 min after pretreatment with the antagonists or V and nine days after surgery. GE was determined 10 min later by measuring the percentage of gastric retention (%GR) of saline labeled with phenol red 10 min after gavage. The %GR (means±SE, n=6) values indicated that BUT abolished the effect of Dp (BUT+Dp vs V+Dp: 35.0%±5.1% vs 56.4%±2.7%) and At (BUT+At vs V+At: 33.5%±4.7% vs 52.9%±2.6%) on GE, and significantly reduced (P<0.05) the effect of AA (BUT+AA vs V+AA: 48.0%±5.0% vs 65.2%±3.8%). ATE, SRA, and sympathectomy did not modify the effects of treatments. These results suggest that β2-adrenoceptor activation occurred in delayed liquid gastric emptying induced by the phenylpyrazole derivatives dipyrone, 4-aminoantipyrine, and antipyrine. Additionally, the released neurotransmitter did not originate in the celiac-superior mesenteric ganglion complex.

Postmarketing pharmacokinetic and pharmacodynamic equivalence of generic and brand atenolol in Egypt

Concerns have raised regarding the postmarketing quality of generic drugs. This study assessed the pharmacokinetic and pharmacodynamic equivalence of generic and brand atenolol tablets in 24 healthy male volunteers in a single-dose, open, randomized, two-period crossover study under fasting conditions. Blood samples were collected for 24 h post dosing and assayed for atenolol using HPLC. Blood pressure and heart rate were measured at baseline and throughout blood sampling. The mean plasma concentration-time curves for both products were similar. Pharmacokinetic and statistical analysis indicated bioequivalence based on the mean ratios of log-transformed Cmax and AUC values. Both products had similar time courses of pharmacodynamic activity with a significant fall in blood pressure and heart rate [maximum after 5 h] followed by a gradual increase towards baseline. Both products were well tolerated. Both atenolol products were bioequivalent in the postmarketing setting and can be used interchangeably in clinical practice

Central 5-HT2A receptors modulate the vagal bradycardia in response to activation of the von Bezold-Jarisch reflex in anesthetized rats

Activation of 5-hydroxytryptamine (5-HT) 5-HT1A, 5-HT2C, 5-HT3, and 5-HT7 receptors modulates the excitability of cardiac vagal motoneurones, but the precise role of 5-HT2A/2B receptors in these phenomena is unclear. We report here the effects of intracisternal (ic) administration of selective 5-HT2A/2B antagonists on the vagal bradycardia elicited by activation of the von Bezold-Jarisch reflex with phenylbiguanide. The experiments were performed on urethane-anesthetized male Wistar rats (250-270 g, N = 7-9 per group). The animals were placed in a stereotaxic frame and their atlanto-occipital membrane was exposed to allow ic injections. The rats received atenolol (1 mg/kg, iv) to block the sympathetic component of the reflex bradycardia; 20-min later, the cardiopulmonary reflex was induced with phenylbiguanide (15 µg/kg, iv) injected at 15-min intervals until 3 similar bradycardias were obtained. Ten minutes after the last pre-drug bradycardia, R-96544 (a 5-HT2A antagonist; 0.1 µmol/kg), SB-204741 (a 5-HT2B antagonist; 0.1 µmol/kg) or vehicle was injected ic. The subsequent iv injections of phenylbiguanide were administered 5, 20, 35, and 50 min after the ic injection. The selective 5-HT2A receptor antagonism attenuated the vagal bradycardia and hypotension, with maximal effect at 35 min after the antagonist (pre-drug = -200 ± 11 bpm and -42 ± 3 mmHg; at 35 min = -84 ± 10 bpm and -33 ± 2 mmHg; P < 0.05). Neither the 5-HT2B receptor antagonists nor the vehicle changed the reflex. These data suggest that central 5-HT2A receptors modulate the central pathways of the parasympathetic component of the von Bezold-Jarisch reflex.

Control of hypertension; efficacy and safety of losartan and atenolol alone and in combination

To compare the efficacy and tolerability of Losartan and Atenolol in alone and combination in treatment of hypertension. Comparative study. Medical out patients department of Jinnah Postgraduate Medical Centre Karachi from January 2007 to June 2007. There were 60 patients previously untreated with mild and moderate essential hypertensions were registered for study. The selected patients were divided into three groups. Group A was given atenolol, Group B was given Losartan, and Group C was given both drugs. The target blood pressure was 120-140/80-90 mmHg. There were 42 males and 18 females with age range 25-65 years. The mean baseline score of groups A, B and C were showed systolic blood pressure 182 +/- 19, 174 +/- 20 and 168 +/- 12 respectively. The diastolic blood pressure was 104.5 +/- 11, 102.5 +/- 9 and 104.5 +/- 10 respectively. The difference in mean systolic and diastolic blood pressure was not significant statistically as P=0.06 and 0.76 respectively. After 4 months of treatment with atenolol, systolic blood pressure decreased to 147 +/- 17, and diastolic blood pressure fell to 87 +/- 4. Losartan decreased systolic blood pressure 138 +/- 13 and diastolic blood pressure 87 +/- 4 in 4 months of treatment. The combined therapy decreased systolic blood pressure 115 +/- 4.6 and diastolic blood pressure 75 +/- 4.7. The effect of treatments on systolic and diastolic blood pressure was significantly different as [p<0.001] and [p 0.036] respectively. Side effects observed in 2 [10%] patients from group C, 8 [40%] in group A and 4 [20%] in group B. Combination therapy proved more effective in controlling hypertension than mono therapy and also fewer side effects. Patients showed better control on combination therapy as compared to mono therapy. Losartan proved a little better in controlling hypertension then atenolol and was more expensive. Patients showed better results with combination therapy for hypertension compared to individual drug

The period between beta-blocker use and physical activity changes training heart rate behavior / O período entre o uso de beta-bloqueador e atividade física mudanças de formação do comportamento da freqüência cardíaca

The Brazilian Society of Cardiology (SBC) proposes that hypertensive subjects who use beta-blockers and practice physical exercises must have their training heart rate (HR) corrected due to the negative chronotropic effect of this drug. Nevertheless, if the physical activity is performed outside of plasmatic half-life, correction may not be necessary. This study investigated the exercise chronotropic response both inside and outside the beta-blocker plasmatic half-life. Nine subjects in use of atenolol or propranolol, and six controls, carried out three walking sessions in three days according to different schedules: EX2 (two hours after drug administration, at the plasmatic peak); EX11 (eleven hours after drug administration, at the end of plasmatic half-life); and EX23 (twenty-three hours after drug administration, outside the plasmatic half-life. The walking sessions were performed on an ergometric treadmill and HR was monitored by a heart rate monitor. During the exercises, mean HRs were 97.2, 108.4 and 109 for EX2, EX11 and EX23, respectively, with the value for EX2 statistically lower than the others (p<0.05). There were no statistical differences in the control group (p>0.05). The study concludes that the attenuation of the positive chronotropic response which occurs during exercise in subjects using beta-blockers, is less evident when the exercise is performed outside the plasmatic half-life of the drug.

A Sociedade Brasileira de Cardiologia (SBC) propõe que os hipertensos que utilizam beta-bloqueadores e praticam exercícios físicos devem ter sua frequência cardíaca de treinamento (HR) corrigida devido ao efeito cronotrópico negativo desse fármaco. Contudo, se a atividade física é realizada fora da meia-vida plasmática do fármaco, a correção pode não ser necessária. Este estudo investigou a resposta cronotrópica ao exercício dentro e fora da meia-vida plasmática do beta-bloqueador. Nove indivíduos que usavam atenolol ou propranolol e seis controles, efetuaram três sessões de caminhada em três dias, de acordo com diferentes esquemas: EX2 (duas horas após a administração do fármaco, no pico plasmático); EX11 (11 horas após a administração do fármaco, no fim da meia-vida plasmática) e EX23 (23 horas após a administração do fármaco, fora da meia-vida plasmática). As caminhadas foram realizadas em esteira ergométrica e a HR foi monitorada por monitor de freqüência cardíaca. Durante os exercícios, as HR médias foram de 97,2, 108,4 e 109, para EX2, EX11 e EX23, respectivamente, com valor de EX2 estatisticamente mais baixo do que os outros (p<0,05). Não houve diferenças estatísticas no grupo controle (p>0,05). O estudo conclui que a atenuação da resposta cronotrópica positiva, que ocorre durante o exercício em indivíduos que utilizam beta-bloqueadores, é menos evidente quando o exercício é realizado fora da meia-vida plasmática do fármaco.

Comparison of hypotensive and hypolipidemic effects of catharanthus roseus leaves extract with atenolol on adrenaline induced hypertensive rats

The leaves extract of Catharanthus roseus was investigated for hypotensive and hypolipidemic effects in adrenaline-induced hypertensive rats [AIHR] and compared with those of Atenolol in a crossover design. The pharmacologically Active components responsible for hypotensive activities were isolated from plant using bioassay guided purification approach and the structure of the compounds was proposed by spectroscopic methods. Catharanthus roseus leaves extract and commercial drug Atenolol were administered through intraperitoneal [i.p] route for one week. Different biochemical parameters such as heart weight, blood glucose level, serum cholesterol level, serum triglyceride level, body weight and the relationships between them were measured. Catharanthus roseus leaves extract at a dose of 30 mg/155 +/- 15 gm of body weight was injected in rat at every morning during the treatment period. The dose of Atenolol was determined according to its pharmacokinetic parameters. Clinically effective plasma concentration as a hypotensive drug was obtained after the injection of 0.1 mg/155 +/- 15 gm of body weight of the drug. The Catharanthus roseus leaves extract made significant changes in each cardiovascular parameter after investigation. Catharanthus roseus leaves extract treated animals have shown the hypotensive effects. Hypotensive effects were also shown by Atenolol

protecting role of beta blokers in cardiac patients in non cardiac surgery

Morbidity and mortality preoperatively mostly caused by cardiovascular events, which the myocardic ischemia form major part of it. This study was carried to assess the protective role of beta-blockers on the heart; by reducing the incidence of mortality and morbidity due to cardiovascular events during major vascular surgery over 6 months follow up post - operatively. High risk patients assigned by clinical finding and positive dobutamine stress echocardiography of 350 patients were. Divided in to two groups, group [1] received standard perioperative care; group [2] received standard care plus atenolol. A total of 350 patients in this study who they have positive clinical finding and positive dobutamine echocardighraphy. 118 patients randomized to receive atenolol, 106 patient to receive standard care, 106 patients excluded because they have been on other beta- blockers, and 20 patients excluded because they have extensive cardiac wall-motion akenisia during rest on stress test. Four patients died of cardiac [3.4%] in atenolol group in comparison to 18 patients [17%] died in the standard group [p<0.02]. Morbidity of nonfatal myocardial infarction in atenolol is [0%] compared with 18 patients [17%] in the standard group [P<0.01]. Atenolol has a significant role in reducing mortality and morbidity in coronary artery disease patients perioperatively especially in high risk patients

Blood pressure lowering effects of antenolol in rats: role of Na-K-ATPase, serum, red cell and tissue electrolytes

Beta adrenoceptor blocking drugs have been shown to decrease the incidence of ventricular fibrillation and sudden cardiac death in patients with coronary artery disease. Although the blood pressure lowering effect of atenolol is studied through hormonal mechanisms. There is no specific study available regarding the role of electrolyte alterations in blood pressure lowering effects of atenolol. The present work was designed to investigate the role of serum, red cell and tissue electrolytes and Na-K-ATPase in blood pressure lowering effects of atenolol [a beta blocking drug]. Rats were divided into two experimental groups. Atenolol [4mg/kg body weight] was administered intraperitoneally to the test group. Control group received same volume of vehicle. Systolic blood pressure was significantly reduced after atenolol administration. An increased membrane Na-K-ATPase activity was observed after atenolol administration. Atenolol treatment decreases sodium and increase potassium in red blood cells. Concentration of sodium, potassium, calcium and magnesium was increased in serum after atenolol treatment. Atenolol treatment decreases sodium and calcium content in heart and kidney tissues whereas an increased content of potassium was observed in these tissue. The results reported in the present study suggest that apart from hormonal mechanism an alteration in electrolytes levels in red cell, serum, heart and kidney tissues and membrane Na-K-ATPase are associated with the blood pressure lowering effect of atenolol. The role of increased activity of Na-K-ATPase in the changes of sodium and potassium in red cell, serum, kidney and heart tissue after atenolol administration is discussed

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.

Behavioural parameters in hypertensives on atenolol therapy.

Behavioural responses which included psychological tests and cold pressor test as a stress test were studied in 20 mild to moderate hypertensives of both sexes, excluding smokers, alcoholics, secondary hypertensives and patients of chronic obstructive pulmonary diseases. Subjects were put on 2 weeks of placebo washout period followed by 6 weeks of treatment with atenolol. Following treatment with atenolol they showed no significant alteration in the scores of psychological tests which included Weschler adult intelligence scale for orientation, while showing significant depression in the rise of heart rate, systolic blood pressure and diastolic blood pressure following cold pressor test. On further analysis, the results showed that hypertensives on placebo had lower scores of memory and attention test as compared to normotensive controls. Besides this, hypertensives on placebo had higher rise of heart rate and systolic blood pressure as compared to normotensive controls after cold pressor test.

A study of pulmonary profile of hypertensive patients--comparison of atenolol vs amlodipine.

Two groups of drugs commonly used for the treatment of hypertension are atenolol and amlodipine. These drugs are reported to have conflicting changes on pulmonary responses. In order to study the effect of hypertension and antihypertensive treatment on pulmonary responses, 40 patients with essential hypertension having diastolic blood pressure between 90-114 mmHg on three consecutive weekly visits were taken. Pulmonary responses were tested at the end of 2 weeks of placebo washout period and then at the end of 6 weeks of treatment with either atenolol or amodipine. Using a computerized autospiror along with the weekly recordings of heart rate and blood pressure, the various pulmonary and cardiac parameters were taken. Analysis of the result showed that atenolol treatment resulted in significant decline of forced vital capacity (FVC), % forced vital capacity (%FVC), and forced expiratory volume in first second (FEV1) whereas amlodipine did not show any significant change on pulmonary parameters.

Effect of prazosin GITS, atenolol, nifedipine SR, and enalapril on ADP-induced platelet aggregation.

A randomized, observer-blind, parallel-group study was carried out to compare the effect of prazosin GITS, atenolol, nifedipine SR, and enalapril on platelet aggregation, measured at a time expected to coincide with trough plasma levels of these drugs. 24 patients (age-30 to 60 yrs) with uncomplicated mild to moderate hypertension who completed a placebo run-in phase successfully were recruited in this study. They were randomly allocated to one of the 4 treatments: prazosin GITS 2.5 mg OD (Group 1), atenolol 50 mg OD (Group II), nifedipine SR 20 mg BD (Group III), and enalapril 5 mg OD (Group IV). All the drugs were given for 7 days, and blood samples were collected at 0 hr on day 1 (pre-treatment) and day 8 (post-treatment). Based on the dose (incremental concentrations of ADP)--response (% maximum aggregation) curve obtained, 2.5 microM/L of ADP was used to compare % inhibition of platelet aggregation among the 4 groups. We found that prazosin GITS inhibited % maximum aggregation significantly (p = 0.02) at 2.5 microM/L of ADP. Such inhibitory effect was not seen in any of the other groups. The inhibition produced by prazosin GITS differed significantly from the action of the other 3 drugs (p < 0.05). This antiplatelet effect of prazosin GITS bears more clinical relevance in view of the fact that it was seen at a time which is expected to coincide with the trough plasma levels of prazosin.

Análise de fármacos em medicamentos por cromatografia líquida de alta eficiência em fase quiral / Pharmaceutical preparations' analysis in drugs by chiral HPLC

Atualmente muitos fármacos empregados na terapêutica são compostos quirais. O propranolol e o atenolol são ß-bloqueadores empregados no tratamento da hipertensão, angina do peito e outros distúrbios cardiovasculares. Estes fármacos são caracterizados pela presença de pelo menos um carbono quiral e são normalmente empregados na forma de racematos. Muitos trabalhos de pesquisa são publicados aplicando a cromatografia líquida de alta eficiência com fase quiral (CLAEFQ) em estudos farmacológicos, mas não em análise quantitativas em formulações farmacêuticas. No presente resumo foi aplicada a técnica da CLAEFQ na separação e determinação quantitativa dos enantiômeros do propranolol e do atenolol em comprimidos. A separação dos enantiômeros foi obtida empregando-se a coluna Chiralcel OD© (250 mm x 4,6 mm, 10 µm), detecção no ultravioleta em 276 nm, para o atenolol em 280 nm, para o propranolol...

O uso da associaçäo de nifedipina e atenolol em formulaçäo galênica única na hipertensäo arterial essencial leve a moderada / Use of nifedipine and atenolol association in a single galenic formulation in the mild-to-moderate essential blood hypertension

Estudamos o efeito anti-hipertensivo por 6 meses de uma formulaçäo galêmica em uma única cápsula da associaçäo de nifedipina 20 mg e atenolol 50 mg administrada uma vez ao dia a 46 pacientes hipertensos essenciais leves e moderados. quando necessário, a dosagem foi aumentada para 40 mg de nifedipina e 100 mg de atenolol (2 cápsulas/dia). Observamos eficácia anti-hipertensivaa em 75,6 po cento dos pacientes com controle pressórico em 51,4 por cento dos hipertensos. que se acompanhou de discreta mas significante bradicardia. O efeito antihipertensivo avaliado pela M.A.P.A. ocorreu nas 24 horas tendo sido predominante no período diurno, sugerindo que, pelo menos para parte dos pacientes, a associaçäo deveria ser administrada em 2 tomadas diárias. A associaçäo dos hipertensores acarretou reduçäo do índice de massa de VE com reduçäo da espessura da parede posterior de VE e do septo interventricular com melhora da relaçäo E/A do enchimento ventricular. O uso desta associaçäo teve um perfil neutro em relaçäo ao metabolismo dos carbohidratos e lípides. A tolerabilidade foi boa, sendo o edema de membros inferiores o principal efeito adverso observado. Concluimos que a associaçäo de nifedipina e atenolol em uma única formulaçäo galênica é útil para o tratamento da hipertensäo arterial essencial leve e moderada.

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.

Efecto inotropico negativo directo de la cocaina en ventriculo de rata / Direct negative inotropic effect of cocaine in rat ventricle strip

Cocaine, when used as a recreative drug, can induce cardiovascular toxic effects such as acute reduction of left ventricle ejection fraction, which indicates a negative inotropic effect of the drug. The purpose of this study was to clarify the direct negative inotropic effect of cocaine in in vitro conditions. Rat right ventricle strips were incubated in Krebs solution gassed with 95 percent O2 and 5 percent CO2 at 37 degrees, and electrically driven with 2 ms square pulses, 17 mA, at 110 systoles/min. Separate experiments were conducted to study cocaine effect at 210 and 310 systoles/min. The contractile force was recorded through a strain-gauge isometric transducer. Cocaine increased contractile force at doses of 0.3-10.0 micrograms/ml, up to 53 percent over basal contraction. In the presence of 4 x 10(-8) Matenolol, low doses of cocaine did not increase contractile force and at doses between 3.0-10.0 micrograms/ml revealed a depressant activity on heart muscle contractions. Doxazosin (1.0 microM) and yohimbine (0.1 microM) did not modify the positive inotropic effect of cocaine, showing that alpha 1 and alpha 2 adrenergic receptors were not involved in this cocaine ventricle action. Increasing ventricle strip stimulation rate to 210 and 310 systoles/min for 30 seconds, the contractile force was risen by 55 percent and 95 percent, respectively. Cocaine at doses 1.0-3.0 micrograms/ml did not modify the physiological increase of contractile force seen upon ventricle rate increase. The mechanism involved in the contractile force increment after ventricle rate increase is a transient rise of cytosolic Ca2+, mainly derived from the sarcoplasmic reticulum and from extracellular fluid. Atenolol (4 x 10(-8) M) exposure of the right ventricle strip intensified the negative inotropic effect of cocaine (3.0-10 micrograms/ml) seen by ventricle stimulation at 210 and 310 systoles/min. The miocardial direct depressant effect of cocaine, in the presence of atenolol, was gradually reversed by extracelular Ca2+ increase at 3.2 and 5.0 mM, respectively. In conclusion, the mechanism of myocardial direct depressant effect of cocaine is related to the beating frequency of the ventricle, which may be sociated to interference with the Ca2+ release process from the myocite sarcoplasmic reticulum, and not to calcium entry blockade from extracellular fluid...