Perspectives in adrenergic beta‐receptor blockade

The pharmacological characteristics of the myocardial adrenoceptor of the mouse have been examined during embryogenesis by measuring ornithine decarboxylase (ODC, EC 4.1.1.17) induction. A four fold elevation of ODC activity was observed after isoprenaline (10 mg/kg, s.c), and enzyme activity was increased two to three fold following adrenaline (1 mg/kg, s.c.) or terbutaline given by direct injection to the foetus (10 μg/500 mg). Pretreatment with the β‐adrenoceptor antagonist, propranolol (10 mg/kg), totally blocked the increase in ODC activity. Elevation of myocardial ODC activity was not inhibited by metoprolol, a relatively specific β1‐adrenoceptor antagonist, at a dose of 10 mg/kg. Since the increase in ODC activity was blocked by a β‐adrenoceptor antagonist (propranolol) and enzyme activity was stimulated by terbutaline, a β2‐agonist, we conclude that β2‐adrenoceptors are selectively coupled to the regulation of murine cardiac ODC activity following catecholamine stimulation.

Section: Resultsmentioning

confidence: 99%

β₂‐ADRENOCEPTORS REGULATE INDUCTION OF MYOCARDIAL ORNITHINE DECARBOXYLASE IN MICE in vivo

Copeland¹,

Larson²,

Roeske³

et al. 1982

“…One of the main uses of 8-adrenoceptor blocking drugs is in the treatment of angina pectoris and the clinical value of propranolol in this condition has been especially well documented (see Fitzgerald, 1969). It is a valuable drug, acting by reducing the oxygen needs of the myocardium and perhaps also by antagonizing the myocardial calorigenic (or " oxygen wasting ") effects of released catecholamines (Shanks, 1967;Parratt, 1969).…”

Section: Introductionmentioning

confidence: 99%

The effect of “selective”β‐adrenoceptor blocking drugs on the myocardial circulation

Parratt

Wadsworth

1970

Summary1. A comparison has been made of the effects of a relatively specific f31-adrenoceptor blocking drug (practolol) and a relatively specific 82-adrenoceptor blocking drug (butoxamine) on myocardial and general haemodynamics in anaesthetized cats. 2. Practolol, in a dose (10 mg/kg, intravenously) which had little effect on arterial pressure, heart rate, myocardial blood flow or myocardial vascular resistance, markedly reduced the effects of isoprenaline infusions on heart rate, aortic dpldt, myocardial blood flow, vascular resistance and metabolic heat production, and the cardiac effort index. Isoprenaline induced vasodepression was unaffected. 3. Butoxamine (5 mg/kg, intravenously) decreased heart rate, aortic dp/dt, the cardiac effort index and myocardial blood flow and increased myocardial vascular resistance. This is taken as further evidence for the existence of /32-adrenoceptors in the myocardial microcirculation. 4. After butoxamine, the effects of isoprenaline on myocardial blood flow, myocardial vascular resistance and heart rate were unaffected but the peripheral vasodilator effect was abolished. The effects on aortic dp/dt and the cardiac effort index were potentiated. 5. It is concluded that the effect of isoprenaline in increasing myocardial blood flow is due predominantly to increased cardiac work and oxygen consumption and that practolol, since it has little direct effect on myocardial blood flow yet abolishes the cardiac stimulant and oxygen wasting effects of released catecholamines, has properties which indicate that it should be an effective and safe anti-anginal drug.

“…The ability to block ,B-adrenoceptors in cardiac muscle has been considered to be the basis of their therapeutic effect (Fitzgerald, 1969). Some of these drugs, notably propranolol, frequently induce respiratory distress in asthmatic subjects, an effect thought to result from block of ,¢adrenoceptors in airways smooth muscle (McNeill, 1964;Richardson & Sterling, 1969 practolol .…”

mentioning

confidence: 99%

The SELECTIVITY OF Β‐ADRENOCEPTOR ANTAGONISTS ON CARDIOVASCULAR AND BRONCHODILATOR RESPONSES TO ISOPRENALINE IN THE ANAESTHETIZED DOG

Daly¹,

Flook²,

Levy³

1975

1The actions of five 1-adrenoceptor antagonists, chosen because of reported differences in their selectivities, were compared using the positive chronotropic, vasodepressor and bronchodilator responses to isoprenaline in anaesthetized dogs. 2 Propranolol was a potent antagonist of the isoprenaline responses in all three systems. 3 Practolol and acebutolol (M & B 17,803) blocked the positive chronotropic responses to isoprenaline to a greater extent than the vasodepressor or bronchodilator responses. 4 Butoxamine and a-methyl dichloroisoprenaline showed the opposite selectivity, blocking the vasodepressor and bronchodilator responses to isoprenaline to a greater extent than positive chronotropic responses. However, both drugs were considerably less potent than the other antagonists studied and their selectivities were less clear-cut than those of practolol or acebutolol. 5 All the antagonists lowered the resting heart rate and to a lesser extent the diastolic blood pressure. The effects of propranolol, practolol and acebutolol on heart rate probably result from cardiac f-adrenoceptor blockade. With butoxamine and a-methyl dichloroisoprenaline, however, the effects on heart rate probably result from a direct cardiodepressant action. 6 The relevance of the results to the problem of the sub-classification of ,B-adrenoceptors is discussed.