1. The beta-adrenoceptor blocking properties of 1-(p-allylphenoxy)-3-isopropylamino-2-propanol hydrochloride (H 64/52) on the cardiovascular and bronchomotor responses to isoprenaline have been determined in the anaesthetized dog.2. H 64/52 selectively blocked the isoprenaline-induced increase in heart rate, contractile force and reduction in airway pressure in the same dose range.3. H 64/52 produced a minimal blockade of vascular beta-adrenoceptors which was apparent only when the isoprenaline-induced fall in diastolic pressure was considered. No significant vascular beta-adrenoceptor blockade with H 64/52 could be shown with the femoral arterial flow or hind-limb perfusion studies.4. These results further support the hypothesis that several different beta-adrenoceptor subtypes exist in the dog. The beta-adrenoceptors subserving cardiac stimulation and bronchodilation appear to be similar and both differ from the beta-adrenoceptor subserving vasodilatation.

Adrenergic beta-Antagonists↗

PubMed1973

The beta-adrenoceptor blocking properties of the alpha-methyl analogues of propranolol and practolol in the anaesthetized dog.

1. The beta-adrenoceptor blocking properties of alpha-methyl propranolol and alpha-methyl practolol were determined in anaesthetized dogs according to their abilities to modify the isoprenaline-induced effects on diastolic pressure, heart rate, myocardial contractile force, femoral arterial blood flow and pulmonary airway resistance.2. alpha-Methyl propranolol shifted the isoprenaline dose-response curves for the fall in diastolic pressure and the positive inotropic and chronotropic responses to the right in a parallel manner yielding pA(2) and slope values of 6.66 (0.92), 6.34 (0.77) and 6.59 (0.61) respectively. The slopes of the graphs for determining pA(2) values for the cardiac beta-adrenoceptor blocking properties of alpha-methyl propranolol were significantly less than 1 and indicated a mechanism other than simple, competitive, reversible antagonism.3. alpha-Methyl propranolol exerted a much weaker blockade of respiratory smooth muscle beta-adrenoceptors than has been reported for propranolol.4. alpha-Methyl practolol exerted a weaker blocking effect on myocardial beta-adrenoceptors than has been reported for practolol. No significant blockade of vascular or respiratory smooth muscle beta-adrenoceptors occurred after a total cumulative dose of 10 mug/kg of alpha-methyl practolol.5. alpha-Methyl substitution of propranolol and practolol reduces the potency but increases the selectivity of their beta-adrenoceptor blocking properties.6. The beta-adrenoceptors subserving cardiac stimulation, vasodilatation and bronchodilatation are representative of three different beta-adrenoceptor sub-types in the dog.

Airway Resistance↗

PubMed1973