The Effect of Propranolol on the Cardiovascular Responses to Isoprenaline, Adrenaline and Noradrenaline in the Anaesthetized Dog

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.

Section: Discussionsupporting

confidence: 81%

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

Daly¹,

Flook²,

Levy³

1975

“…Propranolol is considered to be a non-selective P-adrenoceptor blocker (Shanks, 1966) and this was confirmed in the present results. Comparison of the 3rd and 4th columns of Table 1 shows that acebutolol and M&B 19421 were more active antagonists at /31-than #2-adrenoceptors and that M&B 16942A was equally effective on both types of receptor.…”

supporting

confidence: 79%

A Comparison of the Bronchoconstrictor and Β‐adrenoceptor Blocking Activity of Propranolol and Acebutolol

Maclagan¹,

Ney²

1980

The bronchoconstrictor and β‐adrenoceptor blocking activity of (±)‐propranolol, acebutolol and two of its analogues were compared in a group of littermate rats. Whilst the analogues of acebutolol had similar bronchoconstrictor potency to propranolol, acebutolol had considerably less activity. No correlation could be found between the degree of bronchoconstriction produced by the four drugs and their β‐adrenoceptor blocking activity in the airway smooth muscle. Acebutolol and its analogues show a wide variation in lipid solubility and membrane stabilizing actions but neither of these properties could be related to the production of bronchospasm.

“…On intravenous administration there is an increase in heart rate, cardiac output and rate of left ventricular ejection; stroke volume may be increased or unchanged; in man diastolic arterial pressure is reduced although mean arterial pressure is unchanged, but in dogs both pressures are reduced (Krasnow, et a!., 1964;Harris. Schoenfeld, Brooks & Weissler, 1966;Shanks, 1966;Noble, Gabe, Trenchard & Guz, 1967). The inhalation of isoprenaline in man increases heart rate and forearm flow (Chamberlain, 1967;Cohen, Keates & Young, 1967) and presumably will produce the other changes in the circulation.…”

Section: Discussionmentioning

confidence: 99%

“…The inhalation of isoprenaline in man increases heart rate and forearm flow (Chamberlain, 1967;Cohen, Keates & Young, 1967) and presumably will produce the other changes in the circulation. The effects of isoprenaline on the circulation result from stimulation of adrenergic ,8-receptors and can be prevented or abolished by propranolol (Harris et al, 1966;Shanks, 1966;Chamberlain, 1967). The present experiments in dogs breathing room air, show that these cardiovascular effects of isoprenaline are similar over a wide dose range (0.02 250 p,g/kg).…”

Section: Discussionmentioning

confidence: 99%

The cardio‐toxicity of isoprenaline during hypoxia

Collins¹,

McDevitt²,

Shanks³

et al. 1969

Self Cite

104

The effects of the intravenous injection of isoprenaline on heart rate and arterial pressure has been studied in dogs artificially respired with room air or with 12% oxygen—88% nitrogen. In dogs breathing room air, isoprenaline in doses from 0.02 to 500 μg/kg increased heart rate and reduced arterial pressure. Ventricular fibrillation was produced in one out of three dogs given 250 μg/kg. This was the only dog breathing room air which was killed by isoprenaline. In dogs breathing room air the repeated intravenous injection at 5‐min intervals of 2.5 μg/kg increased heart rate and reduced arterial pressure. No ill effects were produced by six doses. In dogs respired with 12% oxygen—88% nitrogen the Pao2 was reduced from 84 to 38 mm Hg with no changes in Paco2. In these dogs death was produced by doses of isoprenaline which in dogs breathing room air produced normal responses. The fatal dose of isoprenaline (10–50 μg/kg) reduced heart rate and arterial and pulse pressures; sinus rhythm persisted until arterial pressure was less than 50 mm Hg. Ventricular fibrillation did not occur; death occurred from cardiac asystole. Death was produced in a similar way in dogs with hypoxaemia by giving four or five doses of isoprenaline (2.5 μg/kg) at 5‐min intervals or by two doses of 25 μg/kg. The final reduction in arterial pressure during a fatal response resulted from a reduction in cardiac contractility. These lethal effects of isoprenaline could be prevented by pretreatment with propranolol.