Effect of clonidine on three types of experimental hypertension and on plasma renin activity in dogs]

Intra-cisternal clonidine (3 microgram/kg) reduced hypertension and cardiac acceleration after defrenation in dogs, but did not act in intra-venous infusion (10 microgram/kg). The renin activity was not modified. Clonidine was always inactive on hypertension after stimulation of visceral afferences or after injection of potassium cyanidine. These results show that a central mechanism was implied in the anti-hypertensive action of clonidine.     

Methyldopa and propranolol or practolol in moderate hypertension.

The effect of a low dose of methyldopa combined with (a) a non-selective and (b) a selective beta-adrenoceptor antagonist was studied in a double-blind crossover trial in 24 carefully selected patients with moderate hypertension (mean initial lying blood pressure 189/117 mm Hg). Each patient received methyldopa 750 mg/day, propranolol 240 mg/day, practolol 600 mg/day, methyldopa 750 mg/day combined with propranolol 240 mg/day, methyldopa 750 mg/day combined with practolol 600 mg/day, and placebo for four weeks each according to a random sequence. After four weeks of therapy the most effective treatment, methyldopa combined with propranolol, reduced lying and standing blood pressures by 36-5/21-4 mm Hg and 44-7/25 mm Hg respectively. Thic combination had similar effects to those of the combination of methyldopa with the cardioselective agent practolol except that it reduced lying diastolic pressure further. The combination was more effective than either treatment alone. No significant differences were found between the effects of propranolol, practolol, or methyldopa at the doses used.     

Influence of the Beta-Adrenergic Antagonists Propranolol, Practolol and Oxprenolol On the Proliferation of Rat Jejunal Crypt Cells

Abstract. Beta-adrenergic blockade by quite large doses of propranolol, practolol and oxprenolol, once or continuously applied, does not influence jejunal crypt-cell proliferation in the rat. After a single i.p. injection of 20 mg/kg propranolol or practolol and even of 100 mg/kg practolol, the mitotic index, the labelling index and the duration of the S phase do not differ between treated and untreated control animals nor between animals treated with the different drugs. Continuous application of 30 mg/kg/d propranolol, practolol or oxprenolol for 7 or 14 days does not affect the mitotic and labelling indices either, nor does it change the duration of the cycle of the jejunal crypt cells and its phases as determined by the percent labelled mitoses method. These results are in contrast to those reported previously by Tutton & Helme (1974).     

Influence of the beta-adrenergic antagonists propranolol, practolol and oxprenolol on the proliferation of rat jejunal crypt cells

Beta-adrenergic blockade by quite large doses of propranolol, practolol and oxprenolol, once or continuously applied, does not influence jejunal crypt-cell proliferation in the rat. After a single i.p. injection of 20 mg/kg propranolol or practolol and even of 100 mg/kg practolol, the mitotic index, the labelling index and the duration of the S phase do not differ between treated and untreated control animals nor between animals treated with the different drugs. Continuous application of 30 mg/kg/d propranolol, practolol or oxprenolol for 7 or 14 days does not affect the mitotic and labelling indices either, nor does it change the duration of the cycle of the jejunal crypt cells and its phases as determined by the percent labelled mitoses method. These results are in contrast to those reported previously by Tutton & Helme (1974).     

Controlled Trial of Oxprenolol and Practolol in Hypertension

In controlled trials of the beta-adrenergic blocking drugs oxprenolol and practolol in hypertension both drugs were well tolerated without side effects and caused statistically significant non-postural reduction of blood pressure. In less than half the patients on eitherdrug the reduction of blood pressure was clinically adequate. No attempt was made to compare the two drugs.     

Clinical Evaluation of Practolol,a New Cardioselective Beta-blocking Agent in Angina Pectoris

In a controlled double-blind study practolol, a new cardioselective beta-blocking drug, was given to 15 patients with angina pectoris, and compared with propranolol 80 mg. q.d.s. The dose of practolol ranged from 200 to 600 mg.b.d. and was decided by initial open titration in individual patients. Though practolol did not influence the incidence of angina or glyceryl trinitrate consumption, it increased the duration of exercise possible in exercise tests and reduced the amount of ischaemic S—T depression in the radiocardiogram during exercise. Propranolol reduced the incidence of angina and, in the exercise tests, increased the amount and duration of exercise but did not affect the degree of S—T depression. Unlike propranolol, practolol did not produce any adverse effects on bronchial smooth muscle. Hence it is concluded that practolol is an effective drug in treating angina, and in the dosage used is of potential value in patients with asthmatic bronchitis and angina. It should, however, be used cautiously in anginal patients with heart failure.     

Possible role of antibody specific for a practolol metabolite in the pathogenesis of oculomucocutaneous syndrome.

The clinical distribution of an antibody to a metabolite of practolol was investigated, particularly in relation to the oculomucocutaneous syndrome. Serum samples were obtained from patients with and without a history of adverse reaction to practolol and two groups of control patients who had never taken the drug. Five patients also participated in a challenge study. The presence of the antibody was found to be related to practolol administration, and antibody activity could be increased by antigenic challenge. The role of this antibody in the pathogenesis of the oculomucocutaneous syndrome remains uncertain. The lesions may be the result of a hitherto unknown type of hypersensitivity response to practolol.     

Double-blind comparison of tolamolol,propranolol, practolol,and placebo in the treatment of angina pectoris.

Forty-two patients with angina pectoris have completed a randomized, double-blind trial comparing tolamolol 100 mg and 200 mg with propranolol 80 mg, practolol 100 mg, and placebo, all given three times a day. Tolamolol 200 mg thrice daily was found to be equivalent to propranolol 80 mg thrice daily in anti-anginal efficacy. Anginal attack rates and trinitrin consumption were significantly reduced by all active treatments as compared with the placebo but tolamolol and propranolol were the most effective. Tolamolol 200 mg thrice daily was most effective in reducing blood pressure, while propranolol was most effective in reducing the resting heart rate. All treatments except the placebo significantly increased the amount of exercise which could be performed before angina appeared (exercise work), while tolamolol 200 mg thrice daily significantly reduced Robinson''s index when compared with all other active agents. The degree of S-T segment depression induced by exercise was significantly lessened by both tolamolol and propranolol but not by practolol or placebo. There was no difference in patient preference between tolamolol and propranolol but tolamolol at both dose levels was preferred to practolol. Both tolamolol and propranolol are potent adrenergic beta-receptor antagonists and equal in anti-anginal efficacy but tolamolol has the advantage of being cardioselective. It is superior to practolol.     

A comparison of the effects of sotalol and of the isomers of practolol on adrenergic nervous activity

Spontaneous activity was recorded from postganglionic cardioaccelerator fibers in cats anesthetized with α-chloralose. The effects of sotalol and the d(+)? and 1(?)? isomers of practolol were examined in these experiments. The 1(?)? isomer of practolol caused a dose- related depression of adrenergic nervous activity while d(+)? practolol had no effect. Sotalol had no influence on nervous discharge. The results suggest that 1(?)? practolol depresses adrenergic nervous activity and that this effect may be important in the antiarrhythmic action of this agent.     

Beta adrenergic receptors and glucagon in seizures from exposure to oxygen at high pressure (OHP)

Previous studies have shown that sympathetic factors and blood glucose are of importance in the development of seizures and lung damage from OHP. In the present study we examined the influence of beta sympathetic agonists and blocking agents and glucagon on OHP toxicity. Rats were exposed to 6 ATA OHP and examined for time-to-seizure and lung damage. Pretreatment with propranolol increased the time-to-seizure by 70% and practolol by 50% without altering gross lung appearance or lung wet wt/dry wt. Propranolol and practolol also prevented brain glycogen depletion prior to seizure which otherwise occurred in subconvulsive exposure to OHP. Isoproterenol and glucagon pretreatment had no effect on time-to-seizure but isoproterenol did increase lung injury. Both practolol and propranolol block the beta-receptor influence on adenyl cyclase-stimulated second messenger production, while both isoproterenol and glucagon activate adenyl cyclase to produce second messenger. Our results may suggest a possible role for second messenger in mediating some of the acute toxic effects of OHP on the CNS.     

The effect of practolol and butoxamine on aortic arch malformation in beta adrenoreceptor stimulated chick embryos.

An equimolar dose of the beta-1 adrenoreceptor antagonist practolol administered to embryonic chicks prevents the induction of aortic arch malformations by isoproterenol. Whereas 3.75 X 10(-9) mole isoproterenol in 5 microliter saline solution induced aortic arch anomalies in 39% of embryos injected at Hamburger-Hamilton developmental stage 26, pretreatment with practolol one to two minutes before catecholamine administration reduced the anomaly rate to to 4%. Practolol when injected alone did not influence survival rate nor did it cause cardiovascular malformations. Probably the most significant result of this study involves the prevention by practolol of aortic hypoplasia and interrupted aortic arch complexes, anomalies frequently induced by isoproterenol when administered at this stage of embryonic chick development. Butoxamine, a beta-2 adrenoreceptor antagonist, did not block the overall effect of isoproterenol nearly as effectively as did practolol. Results from the present study suggest that aortic arch anomalies may be induced in embryonic chicks via beta-1 adrenoreceptor stimulation. Beta-2 receptor stimulation does not appear to be as significantly involved.     

Changes of small bowel motility and noradrenaline content of the intestinal wall in response to alpha- and beta-adrenergic blockade in dog

In experiments on dogs, the spontaneous movements of the small bowel were in all cases enhanced by the alpha 2-blocker phentolamine, while they were not influenced, or were slightly decreased, by the beta 1-blocker practolol. Neither drug caused a change in the noradrenaline content of the intestinal wall. In the same animals, the joint administration of phentolamine and practolol led to a considerable increased small bowel motility, and to a significant decrease in the noradrenaline level of the intestinal wall. The results are in agreement with experimental data indicating that presynaptic alpha-receptors play a primary role in the sympathetic regulation of small bowel motility.     

Mechanism of action of βadrenergic receptor blocking agents in angina pectoris: Comparison of action of propranolol with dexpropranolol and practolol

The effect on exercise tolerance of racemic propranolol has been assessed in eight angina pectoris patients and compared with that of dexpropranolol (the dextro isomer of propranolol), practolol (I.C.I. 50172), and saline. Dexpropranolol has the same local anaesthetic action as propranolol with negligible β-adrenergic receptor blocking activity, while practolol is a cardio-selective β-adrenergic blocking agent which does not have local anaesthetic activity.Saline and dexpropranolol had no significant effect on exercise time; racemic propranolol and practolol improved exercise tolerance in six subjects, the response to the two drugs being very similar in individual patients. It was concluded that the beneficial effect of propranolol in angina pectoris results from its action as a β-adrenergic receptor blocking agent and is not due to its local anaesthetic, or quinidine-like, activity.     

Pharmacodynamics of Practolol in Chronic Renal Failure

Plasma levels of practolol were measured in advanced chronic renal failure. The plasma half life was found to be markedly prolonged. During haemodialysis considerable shortening of the half life occurred. Therapeutic blood levels of practolol can be achieved in maintenance haemodialysis patients by the administration of 200 mg of the drug by mouth at the beginning and end of each dialysis.     

Effect of atenolol on ventilatory and cardiac function in asthma.

The effects on ventilatory and cardiac function of atenolol, a new cardioselective beta-adrenoceptor blocking agent, were compared with those of practolol in a double-blind trial in 12 patients with asthma. Both drugs impaired ventilatory function--atenolol insignificantly and practolol significantly. Atenolol was if anything more cardioselective than practolol. Neither drug interfered significantly with the bronchodilator response to inhaled isoprenaline. Atenolol is suitable for use in patients for whom practolol would formerly have been chosen because of its cardioselectivity.     

缓冲神经在电针抑制犬急性实验性高血压中的作用

在切除双侧窦神经与主动脉弓神经的慢性犬,血压很快回复至对照水平,但较易波动。在此种犬静脉匀速注射去甲肾上腺素造成高血压状态时,电针“足三里”不再有明显降压作用。在麻醉犬静脉勻速注射去甲肾上腺素时,肾交感冲动随血压上升而受到明显抑制,然后在16分钟内逐渐回升。血压上升时呼出气 CO_2百分比明显升高,伴随动脉血 CO_2分压升高而 O_2分压降低。在切除缓冲神经后再注射去甲肾上腺素时,肾交感冲动未见明显变化。在清醒犬静脉匀速注射去甲肾上腺素时,动脉血 O_2分压也有明显降低,而注射苯肾上腺素时,血 O_2分压很少改变。电针“足三里’对苯肾上腺素性高血压的降压作用不明显。且心得安可阻断电针对去甲肾上腺素性高血压的降压作用。此外,电针能抑制山梗菜碱所致的化学感受性升压反射,此种抑制作用可为静脉注射纳洛酮所阻断。结果表明,去甲肾上腺素除能收缩血管升高血压,增加压力感受性传入冲动外,还能刺激新陈代谢,改变血液气体成分而引起化学感受性升压反射。电针“足三里”主要因能抑制化学感受性反射而能降压,仅有压力感受性传入冲动的增多并不能使电针具有明显降压效应。     

Practolol in Treatment of Angina Pectoris. A Double-blind Trial

Twenty-four patients with angina pectoris entered a double-blind trial of the cardioselective beta-adrenergic blocking agent practolol. Seventeen experienced less angina and consumed fewer glyceryl trinitrate tablets when on the active preparation. There was also a decrease in the mean number of attacks suffered by patients while on practolol and a reduction in the number of glyceryl trinitrate tablets taken. These results are of statistical significance at, at least, the 5% level.     

Metabolites of procainamide and practolol inhibit complement components C3 and C4.

Drug-induced systemic lupus erythematosus arises from toxic side-effects of administration of hydralazine, isoniazid, procainamide and practolol. Hydralazine and isoniazid are nucleophilic drugs and inhibit the covalent binding reaction of complement components, C3 and C4, an effect likely to lead to deposition of immune complexes (a feature of systemic lupus erythematosus). Procainamide and practolol do not themselves inhibit C3 and C4. A range of metabolites and putative metabolites of procainamide and practolol were synthesized, and tested for their ability to inhibit the covalent binding reactions of C3 and C4. The highly nucleophilic hydroxylamine metabolite of procainamide was strongly inhibitory in both tests, as was a putative hydroxylamine metabolite of practolol. These studies indicate a potential role for the hydroxylamine metabolites in mediating the toxic side-effects of procainamide and practolol, and emphasize the need for adequate measurements of hydroxylamine metabolites in human tissue.     

Beta1 and beta2 receptor mechanisms in rat jugular veins: differences between norepinephrine and isoproterenol-induced relaxation.

The rat jugular vein possesses both beta₁ and beta₂ adrenergic receptors based on the use of two beta₁ antagonists, practolol and atenolol and two beta₂ antagonists, butoxamine and N-isopropylmethoxamine. In this vessel, norepinephrine and nylidrin interact primarily with beta₁ receptors whereas isoproterenol and salbutamol interact with both beta₁ and beta₂ receptors showing a slight preference for beta₂ receptors. Isoxsuprine-induced relaxation was not blocked by either beta₁ or beta₂ antagonists. Selectivity of norepinephrine for beta₁ receptors and of isoproterenol for beta₂ receptors also occurred in circular preparations of the portal vein after alpha adrenergic blockade. However, after alpha adrenergic blockade in rat aorta, practolol and N-isopropylmethoxamine were equieffective as antagonists of relaxation to norepinephrine and isoproterenol although N-isopropylmethoxamine was somewhat more effective than practolol.     

Role of adrenergic mechanisms in the development of cardiac hypertrophy.

This experiment was designed to study the role of cardiac beta-adrenergic mechanisms in the development of hypertrophy in rats. The suprarenal abdominal aorta was banded, resulting in an increase in cardiac wt-body wt ratio. A group of rats received a sham operation. Half of the banded rats were treated with practolol, 2.0 mg/kg intraperitoneally every 12 hr for the 6 days after banding. The effectiveness of cardiac beta-adrenergic blockade was confirmed by absence of an increase in heart rate following intravenous isoproterenol at various times between practolol injections. Practolol did not affect the gradient in the banded groups. Six animals in each banded group were sacrificed daily for 6 days. The right and left ventricles were dissected separately and weighed. RV-body weight ratios increased similarly in both banded groups. LV-body weight ratio (g/kg) was 2.17 +/- 0.043 in sham rats, and it attained maximal levels of 3.03 +/- 0.10 within 6 days in banded untreated rats and 2.96 +/- 0.14 in banded rats receiving practolol. Therefore, beta-adrenergic mechanisms were not involved in the development of hypertrophy due to increased afterload. Also, these findings are not consistent with the Meerson hypothesis, since hypertrophy occurred despite the reduction in myocardial O2 consumption due to practolol.