Effects of clonidine, prazosin and phentolamine on heart rate and coronary sinus catecholamine concentration during cardioaccelerator nerve stimulation in spinal dogs.

British Journal of Pharmacology (Impact Factor: 5.07). 11/1979; 67(2):283-92. DOI: 10.1111/j.1476-5381.1979.tb08678.x
Source: PubMed

ABSTRACT 1 In spinal dogs, continuous electrical stimulation of the cardioaccelerator nerve produced a transient rise in aortic blood pressure and a sustained increase in both heart rate and coronary sinus blood flow. The latter effects were accompanied by a significant elevation in the coronary sinus plasma noradrenaline concentration without significant changes in the levels of dopamine and adrenaline. The concentrations of the three catecholamines in thoracic aorta plasma were not significantly changed by cardioaccelerator nerve stimulation.2 Clonidine (20 mug/kg, i.v.), given during cardioaccelerator nerve stimulation, increased both mean aortic blood pressure and coronary sinus blood flow and decreased heart rate and coronary sinus venous plasma noradrenaline overflow.3 Phentolamine (0.3 mg/kg, i.v.) completely antagonized these effects of clonidine. Prazosin (0.3 mg/kg, i.v.) inhibited by only 43 and 38% the respective reductions in heart rate and noradrenaline overflow elicited by clonidine.4 On termination of cardioaccelerator stimulation (about 10 min after either prazosin or phentolamine), heart rate and coronary sinus noradrenaline overflow returned to control prestimulation levels.5 Phentolamine or prazosin, administered alone during stimulation of the cardioaccelerator nerve, increased heart rate and noradrenaline overflow into the coronary sinus plasma. However, intravenous phentolamine and prazosin, in contrast to desipramine (0.3 mg/kg, i.v.) or tyramine (1.0 mg, i.a.), failed to change the tachycardia resulting from the local administration of noradrenaline into the sinus node artery (i.a.).6 These results show that in spinal dogs the clonidine-induced reduction in heart rate (elevated by electrical stimulation of the cardioaccelerator nerve) is accompanied by a fall in the quantity of noradrenaline overflowing into the coronary sinus plasma. The latter effect is presumably the result of an action of clonidine on cardiac presynaptic alpha-adrenoceptors, the activation of which is followed by a reduction in the release of noradrenaline per nerve impulse. Phentolamine and prazosin are both antagonists of cardiac presynaptic alpha-adrenoceptors in spinal dogs, as suggested by their action against clonidine and by their positive chronotropic effect when administered during stimulation of the cardioaccelerator nerve.

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    ABSTRACT: We studied pressor responses and changes in plasma catecholamine concentrations following two consecutive doses of ephedrine 0.1 with (n = 20) and without (n = 20) clonidine 5 premedication in patients presenting for a variety of major surgical procedures under general anaesthesia. Arterial blood pressure and heart rate were measured at 1 min intervals for 10 min, and plasma catecholamines were measured before and 3 min after each dose of ephedrine. Mean blood pressure changes from the baseline values were greater in the clonidine than in the control group 3-8 min and 4-9 min following the first and the second doses of ephedrine, respectively (p < 0.05). Plasma catecholamine concentrations tended to be lower in the clonidine group throughout the study. The augmented pressor response to ephedrine in clonidine-treated patients can be attributed to enhanced cardiovascular response rather than clonidine-induced accumulation and subsequent increased release of catecholamine.
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    ABSTRACT: Increased heart rate and left ventricular pressure during humoral and neuronal adrenergic activation act to restrict blood flow preferentially in the subendocardium. The hypothesis was advanced that alpha-adrenergic coronary vasoconstriction preferentially in the subepicardium may counterbalance the enhanced extravascular compression in the subendocardium and serve to maintain blood flow transmurally uniform. In 40 anesthetized dogs, regional myocardial blood flow was determined with colored microspheres; wall function, with sonomicrometry. Humoral adrenergic activation (HAA) was induced by a combination of intravenous atropine, intravenous norepinephrine, and atrial pacing during baseline coronary vasomotor tone (group 1, n = 6) and in the presence of maximal coronary vasodilation with intravenous dipyridamole (group 2, n = 6). In an additional group, HAA was induced by intravenous norepinephrine in the presence of dipyridamole but without atropine and atrial pacing in order to increase end-diastolic left ventricular pressure (group 3, n = 6). Measurements were performed at rest, during HAA, and during ongoing HAA with the intracoronary infusion of the alpha-antagonist phentolamine (Phen). At unchanged mean aortic pressure, Phen improved blood flow particularly to the inner layers as follows: from 1.42 +/- 0.40 (mean +/- SD) to 1.90 +/- 0.40 mL/(min.g) (group 1, P < .05), from 4.99 +/- 2.31 to 5.53 +/- 2.56 mL/(min.g) (group 2, P < .05), and from 6.01 +/- 1.41 to 6.29 +/- 1.27 mL/(min.g) (group 3, P < .05), associated with a decrease in outer layer blood flow in groups 2 and 3. In 16 additional dogs, beta-adrenoceptors were blocked by propranolol and muscarinic receptors by atropine. Neuronal adrenergic activation (NAA) was induced by cardiac sympathetic nerve stimulation (CSNS) during baseline coronary vasomotor tone (group 4, n = 8) and in the presence of maximal vasodilation (group 5, n = 8). Measurements were performed at rest, during a first CSNS, and 20 minutes later during a second CSNS+Phen. The reproducibility of two consecutive episodes of CSNS 20 minutes apart was demonstrated in a separate set of experiments (n = 6). At matched mean aortic pressures, Phen improved blood flow to all myocardial layers in group 4, whereas in group 5, Phen induced a redistribution of myocardial blood flow toward subepicardial layers [from 4.44 +/- 0.96 to 4.81 +/- 0.83 mL/(min.g), P < .05] at the expense of inner layers. With the addition of Phen, there was no change in regional wall function in any group of dogs studied. Thus, during HAA, alpha-adrenergic coronary vasoconstriction does not exert a beneficial effect on transmural blood flow distribution. During NAA, a beneficial effect of alpha-adrenergic coronary vasoconstriction becomes apparent only under conditions of maximal coronary vasodilation.
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