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PubMedDate not supplied

The influence of the intrinsic sympathomimetic activity of beta-adrenoceptor antagonists on haemodynamic effects in anaesthetized dogs.

1. The effects of propranolol, atenolol (ICI 66,082), practolol and pindolol on heart rate and maximal left ventricular dp/dt, atrioventricular conduction time, mean aortic flow and diastolic blood pressure during cardiac pacing were investigated over a wide dose range (0.025-4.0 mg/kg, i.v.) in dogs anaesthetized with pentobarbitone.2. Propranolol and atenolol produced similar reductions in haemodynamic parameters. Propranolol had no further effect in dogs pretreated with atenolol. 3. Practolol tended to cause smaller reductions in the haemodynamic parameters than either propranolol or atenolol. Subsequent administration of propranolol still had some depressant activity. 4. Pindolol produced a biphasic response, with depression of cardiac function at the low doses (0.025 and 0.1 mg/kg), but a reversal of effect as the dose was increased. 5. It is therefore concluded that, in anaesthetized dogs, the intrinsic activity of practolol and pindolol limits the fall in heart rate, cardiac conduction, aortic flow and maximal dp/dt observed with beta-adrenoceptor blockade. With pindolol, however, the influence of intrinsic activity is observed only in high doses related to beta-adrenoceptor blockade.

Adrenergic beta-Antagonists↗
PubMed1994

The effects of sympathomimetics on the cardiovascular system of sheep.

1. Sheep hearts have been used to study the effects of beta-adrenoceptor (beta-AR) agonists in order to better understand the effects of common asthma treatment drugs on heart rate, cardiac power output and cardiac pathology. Hearts have been examined both in vivo and in vitro. 2. In whole anaesthetized sheep, isoprenaline, fenoterol and salbutamol induced dose-dependent increases in heart rate. Hypokalaemia in response to salbutamol was accentuated in hypoxia. Many of these hearts showed significant myocardial lesions. Hypoxia alone caused no significant cardiac response. 3. As expected, the beta 1-AR agonist dobutamine caused dose-dependent increases in heart performance (heart rate and cardiac power output). Both responses were blocked by metoprolol and propranolol. The beta 2-AR agonist salbutamol caused dose-dependent increases in heart rate and although cardiac output increased, cardiac power output remained unchanged as a consequence of the fall in peripheral resistance. The heart rate changes were blocked by metoprolol. Importantly, propranolol blocked both the heart rate response and the fall in peripheral resistance. 4. Isolated atrial strips showed a right shift of their dose-response curve to isoprenaline in the presence of the highly selective beta 2-AR antagonist ICI 118,551 at concentrations above 1 x 10(-8) mol/L. 5. We conclude that the sheep heart shows many pharmacological characteristics of the human heart which makes it a good pharmacological model in addition to its being amenable to many common techniques available for humans.

Albuterol↗
PubMed1958

Sensitization of the heart and nictitating membrane of the cat to sympathomimetic amines by antihistamine drugs.

Sensitization to the cardio-accelerator action of adrenaline and noradrenaline by five antihistamines was examined on the acutely denervated heart of the cat. Antazoline (Antistin), chlorcyclizine and promethazine (Phenergan) increased the cardio-accelerator responses to both amines equally. Mepyramine (Anthisan) increased noradrenaline more than adrenaline action. Diphenhydramine (Benadryl) resembled cocaine in potentiating the responses to noradrenaline but not to adrenaline.On the nictitating membrane mepyramine caused sensitization to the actions of adrenaline, noradrenaline and tyramine, an effect similar to that of chronic preganglionic denervation. Diphenhydramine enhanced the action of noradrenaline more than that of adrenaline and had little effect on tyramine action, giving a sensitization which bears a greater resemblance to the type caused by cocaine or chronic postganglionic denervation.It is suggested that two distinct mechanisms are required to account for the phenomena of sensitization.

Amines↗
PubMed1962

A comparison between the effects of a tetanus and the effects of sympathomimetic amines on fast- and slow-contracting mammalian muscles.

The effects of adrenaline and isoprenaline on the tension and time-course of the contractions of the tibialis anterior and soleus muscles of cats and rabbits have been compared with the effects of previous high-frequency stimulation. Like a tetanus, adrenaline possessed a facilitating action on neuromuscular transmission and an action exerted directly on the muscle fibres. Isoprenaline possessed only the second of these two actions. The effect of adrenaline and isoprenaline on the muscle fibres was blocked by dichloroisoprenaline and by 1-(2 naphthyl)-2-isopropylaminoethanol, whereas the effect of adrenaline on neuromuscular transmission was blocked by phentolamine and by phenoxybenzamine. In the soleus muscle, both the catechol amines and a previous tetanus caused similar decreases in maximal twitch tension and in the times to peak tension and to half-relaxation. The muscle action potentials were unaltered or slightly increased in amplitude. In the tibialis anterior muscle, a previous tetanus and the catechol amines caused an increase in twitch tension and an increase in the overall duration of the twitch. The muscle action potentials were either unchanged or were slightly decreased in amplitude. In this muscle the effect of a tetanus differed from that of the catechol amines in that the large post-tetanic change was associated with a marked increase in the rate of rise of twitch tension.

Animals↗
PubMed1963

Action of sympathomimetic drugs on the isolated junction of the bile duct and duodenum.

The actions of adrenaline, noradrenaline and phenylephrine were studied both on the terminal tract of bile duct (prepared as spiral strips or intact) and on the adjacent duodenum taken from the calf and the cat. These amines contract the terminal bile duct and relax the duodenum. Furthermore, on the basis of the action of some adrenaline antagonists, the hypothesis is advanced that there are alpha-receptors which mediate contraction of muscle in the sphincterial zone of the bile duct.

Animals↗
PubMed1964

THE ACTION OF SYMPATHOMIMETIC AMINES ON THE OUTFLOW OF AQUEOUS HUMOUR FROM THE EYE.

The actions of adrenaline, noradrenaline and isoprenaline on the resistance to outflow of aqueous humour from the rabbit eye are described. In some experiments, correlations have been made with pupil diameter. Intravitreous injections of adrenaline, noradrenaline and large doses of isoprenaline decreased the resistance to outflow of fluid from the eye and dilated the pupil. Intravitreous injection of phentolamine was without effect on the intraocular pressure and resistance to outflow of aqueous humour, although such injections resulted in miosis. The actions of adrenaline, noradrenaline and large doses of isoprenaline on the outflow resistance were antagonized by phentolamine. Postganglionic sympathetic denervation did not affect the aqueous humour dynamics when the eyes where examined 2 weeks later, but all the denervated eyes exhibited miosis at this time. Much smaller doses of noradrenaline were required to lower the intraocular pressure and decrease the resistance to outflow of aqueous humour in the denervated eyes; in addition, the dose/response curve for the effect of noradrenaline on the outflow resistance was shifted to the left in these experiments. These results support the view that adrenaline alpha-receptors are associated with the resistance to outflow of aqueous humour from the rabbit eye.

Animals↗