Effects of Pronethalol on the Cardiovascular Actions of Catecholamines During Blockade by Phenoxybenzamine

Abstract

This paper presents the results of experiments in which some cardiovascular parameters of the anaesthetized dog were recorded, in an attempt to elucidate the mechanisms involved. METHODSSeventeen mongrel dogs of either sex weighing between 8 and 18.5 kg were anaesthetized with pentobarbitone sodium (30 mg/kg, intravenously) and both vagi were cut in the neck. Blood pressure was measured with a Statham transducer (model P23AA) and a carrier preamplifier from a cannula in the left carotid artery. During artificial ventilation, thoracotomy was performed, a pericardial cradle was prepared and a Walton-Brodie strain gauge arch was sutured to the right ventricle and connected to another carrier preamplifier. After heparinization (5 mg/kg followed by 2 mg/kg at 45 min intervals), blood flow in the femoral artery was measured by means of a Shipley-Wilson type rotameter (Blood Flow Assembly).All measurements were recorded on a Physiograph Six (E & M Instrument Co.). Heart rate was measured from the original tracings.After obtaining control responses to intravenous injections of suitable doses of adrenaline, noradrenaline and isoprenaline and to close intra-arterial injections of adrenaline and isoprenaline (0.25 to 16 alg doses), the animals were treated with phenoxybenzamine (5 mg/kg) and these procedures repeated 30 min later. Catecholamine administration was once more repeated some minutes after pronethalol (5 mg/kg) was given. Six dogs received, instead of injections, adrenaline or noradrenaline by intravenous infusion from a constant rate pump (Braun), over a period of 4 min (5 ,ug/kg/min). In some animals 883 F (diethylaminomethylbenzodioxane hydrochloride) (5 mg/kg) was administered at the end of the experiment.Drugs. Phenoxybenzamine hydrochloride (Smith, Kline & French) was dissolved to a concentration of 10 mg/mi. in propylene glycol acidified by concentrated hydrochloric acid in order to obtain * Since deceased.

Reversal by pronethalol of dibenamine blockade: a study on the seminal vesicle of the guinea‐pig

“…Eltherington & Horita (1960) observed that after blockade of the vascular areceptors by phenoxybenzamine, injection of the 8-receptorblocking agent dichloroisoprenaline (DCI) caused a return of the adrenaline pressor response to approximately 50% of the control value. Moreira & Osswald (1965), Gulati, Gokhale & Udwadia (1965), Tuttle (1965) and Garrett, Malafaya-Baptista & Osswald (1966) confirmed this observation on the blood pressure and demonstrated that this action of DCI extended to the nictitating menmbrane and to the femoral blood flow; it was also observed with other s-receptor blocking agents. Although tentative explanations have been suggested, the meclhanism of this phenomenon remains controversial, in view of the complexity of the cardiovascular parameters.…”

“…Since the reversal was obtained only with concentrations of di'benamine which cause a parallel shift of the dose-effect curves to the right and was not observed in the presence of higher concentrations of dilbenamine, which produce unsurmountable antagonism, one could speculate, as Garrett et al (1966) have done, that " spare receptors" are involved in the reversal phenomenon.…”

“…Gulati et al (1965) ascribed the reappearance of the pressor action of adrenaline and noradrenaline to a direct reversal of the blocking action of pronethalol on a-tecdptors occupied by phenoxybenzamine, while Moreira & Osswald (1965) and Garrett et al (1966) suggested that the reversal was due to the occupation of unoccupied a-receptors by adrenaline diverted from the 3-receptors by the blocking effects of pronethalol. These interpretations were based on results obtained by measurement of arterial blood pressure which may be influenced by multiple factors.…”

“…Eltherington & Horita (1960) observed that after blockade of the vascular areceptors by phenoxybenzamine, injection of the 8-receptorblocking agent dichloroisoprenaline (DCI) caused a return of the adrenaline pressor response to approximately 50% of the control value. Moreira & Osswald (1965), Gulati, Gokhale & Udwadia (1965), Tuttle (1965) and Garrett, Malafaya-Baptista & Osswald (1966) (1968) on the rat vas deferens. These structures, however, are not preparations of choice, because aortic strips and the vas deferens have both a-and a8-receptors.…”

Effects of Beta-Adrenergic Receptor Blocking Agents on Blood Pressure in Conscious Hypertensive Rats

“…From the results with antagonistic action between the alpha and beta-blocking agents, Olivares et al suggested that beta-blocking agents "un blocked" the alpha-receptor which had been previously blocked by the alpha-blocking agent (15). On the other hand, it has been suggested that in tissues with alpha and beta receptors, the beta-blockade subsequent to alpha-blockade results in unmasking of re sidual alpha-adrenergic activity of the agonists with mixed activity, not previously blocked by the alpha-blocking agent (16)(17)(18)(19).…”