Comparison of the bronchodilator and cardiovascular actions of salbutamol, isoprenaline and orciprenaline in guinea‐pigs and dogs

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: Preparation Of Animalsmentioning

confidence: 99%

“…Pulmonary resistance was measured as described by Daly et al (1971). A dose of acetylcholine, selected to give a submaximal increase of approximately 3-fold in pulmonary resistance, was administered intravenously at 5 min intervals until constant responses were obtained.…”

Section: Preparation Of Animalsmentioning

confidence: 99%

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

Daly¹,

Flook²,

Levy³

1975

“…The attenuation of the vasodilator responses to intra-arterial noradrenaline and adrenaline by propranolol (Figure 1) and the consequent potentiation of the hepatic arterial vasoconstrictor responses to these catecholamines, particularly to adrenaline (Figure 3 adrenoceptor stimulant, salbutamol (Daly, Farmer & Levy, 1971) and the selective P,B-adrenoceptor antagonist atenolol (Hainsworth et al, 1974).…”

Section: Assessment Ofdrug Effectsmentioning

confidence: 99%

“…These experiments revealed the presence of P-adrenoceptors which were stimulated to cause hepatic arterial vasodilatation by isoprenaline and also by adrenaline and noradrenaline, but not by phenylephrine. Subsequently, the nature of the fl-adrenoceptors in this vascular bed was examined by using the selective /2-adrenoceptor stimulant salbutamol (Daly, Farmer & Levy, 1971) and the selective P,-adrenoceptor antagonist atenolol (ICI 66082) (Hainsworth, Karim & Stoker, 1974).…”

Section: Introductionmentioning

confidence: 99%

The ROLE OF Β‐ADRENOCEPTORS IN THE RESPONSES OF THE HEPATIC ARTERIAL VASCULAR BED OF THE DOG TO PHENYLEPHRINE, ISOPRENALINE, NORADRENALINE AND ADRENALINE

Richardson

Withrington

1977

1 The sympathetically-innervated hepatic arterial vascular bed of the dog was perfused from a femoral artery. Hepatic arterial blood flow and perfusion pressure were recorded continuously, and the hepatic arterial vascular resistance (HAVR) calculated from these measurements.2 Intra-arterial injections of phenylephrine caused dose-dependent rises in HAVR, indicating hepatic arterial vasoconstriction, at all doses above threshold. No secondary reductions in HAVR followed these responses.3 Intra-arterial injections of isoprenaline caused only dose-dependent reductions in HAVR at doses above threshold. 4 Intra-arterial injections of noradrenaline typically caused an initial increase in HAVR which was followed at all but the highest doses by a secondary, delayed, reduction in HAVR.5 Intra-arterial injections of adrenaline, like those of noradrenaline, resulted in hepatic arterial vasoconstriction followed by hepatic arterial vasodilatation.6 On a molar basis, the most potent hepatic arterial vasoconstrictor was noradrenaline, followed by adrenaline and phenylephrine.7 The maximum reductions in HAVR caused by adrenaline (mean reduction = 21.9%) and noradrenaline (16.9%) were significantly smaller than those due to isoprenaline (P< 0.001).8 Propranolol attenuated the hepatic arterial vasodilator responses due to isoprenaline, and the secondary falls in HAVR following intra-arterial adrenaline and noradrenaline. 9 Propranolol did not modify the vasoconstrictor responses to phenylephrine. 10 Both adrenaline and noradrenaline were more potent hepatic arterial vasoconstrictors after propranolol than in the absence of /B-adrenoceptor blockade. The potentiation of the vasoconstrictor effects of adrenaline was statistically significant. 11 After propranolol, adrenaline was a more potent hepatic arterial vasoconstrictor than noradrenaline.12 Since the P-adrenoceptors in the hepatic arterial vasculature were not blocked by atenolol, but were stimulated by salbutamol, it is concluded that they are predominantly of the P2-type. 13 The vasoconstrictor actions of phenylephrine, noradrenaline and adrenaline were all antagonized by the systemic administration of phentolamine, all three dose-response curves being shifted to the right. ' 14 The results are discussed with regard to the possible control of the hepatic arterial vasculature by naturally-occurring catecholamines.

“…Because the technique is non-invasive, no measurements of blood pressure or heart rate were made; nonetheless, salbutamol was assumed to have been given in an effective dose (0.1 mg/kg) because it was much higher than has been reported to cause bronchodilation in dogs (Daly, Farmer & Levy, 1971). Kneussel & Richards (1977) showed that a-adrenoceptors were present in the tracheal and bronchial smooth muscle of tissue only from patients with chronic obstructive pulmonary disease, but normal human or canine airway muscle did not respond to noradrenaline, suggesting that there is usually an absence of a-adrenoceptors in this tissue.…”

Section: Discussionmentioning

confidence: 99%

A Model of Reflex Tracheal Constriction in the Dog

Allott

Evans

Loveday

et al. 1980

A tracheal pouch with its nerve and blood supply intact has been prepared in situ in dogs. Mechanical stimulation of the upper airways in dogs anaesthetized with chloralose induced a consistent increase in pouch pressure which was abolished by bilateral vagal section. The response of the pouch following mechanical stimulation of the airways was abolished by intravenous pentobarbitone, atropine, administered systemically or when present in the pouch, and tetracaine, applied to the stimulus area or when present in the pouch. Salbutamol had no inhibitory effects on the response regardless of its route of administration. These results suggest that the increase in pouch pressure following mechanical stimulation of the upper airways is mediated by a vagal reflex arc. The technique may distinguish between drugs the site of action of which is at the afferent or efferent end of this reflex arc.