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In pentobarbital-anesthetized normotensive dogs, clonidine (20.0 micrograms/kg i.v.), in contrast to pergolide (30.0 micrograms/kg i.v.), reduced significantly both aortic blood pressure and plasma concentration of norepinephrine. However, in dogs that had been made hypertensive by sectioning the vagi and carotid sinus nerves, pergolide, like clonidine, lowered the blood pressure and plasma concentrations of epinephrine and norepinephrine that were enhanced markedly by deafferentation. Furthermore, in this preparation pergolide decreased the calculated resistance in vascular regions supplied by the upper abdominal aorta and the innervated femoral and renal arteries, but it increased vascular resistance in the denervated hind leg. Pergolide (1.0 microgram/kg) injected intracisternally (i.c.m.) induced a fall in blood pressure of comparable magnitude to that produced by a 30 times higher i.v. dose. Intravenously and i.c.m. administered pergolide lowered blood pressure by acting at distinct anatomical sites inasmuch as i.v. sulpiride blocked the effects of i.v. but not i.c.m. pergolide. The combination of sulpiride plus yohimbine injected i.c.m. was necessary to abolish the decrease in blood pressure evoked by i.c.m. pergolide. In atropinized spinal dogs, i.v. pergolide inhibited the vasoconstriction elicited by electrical stimulation of the lumbar sympathetic chain, an effect which was antagonized by sulpiride. Similarly, pergolide (30.0 micrograms/kg i.v.) like clonidine, reduced the heart rate and coronary venous plasma norepinephrine concentration raised by sustained electrical stimulation of the cardioaccelerator nerve. Sulpiride, but not phentolamine, antagonized this pergolide-induced inhibition of sympathetic nerve function. In chlorisondamine-pretreated dogs, pergolide produced a transient pressor response due to stimulation of postsynaptic vascular alpha-2 adrenoceptors. In conclusion, the failure of i.v. pergolide to decrease aortic blood pressure in pentobarbital-anesthetized normotensive dogs is presumably due to the inability of pergolide to produce a significant inhibition of the vascular sympathetic tone in this preparation. However, in neurogenic hypertensive dogs which are characterized by an elevated level of sympathetic drive, i.v. pergolide reduced blood pressure and aortic plasma norepinephrine concentration. These effects of pergolide are compatible with a DA-2 dopamine receptor stimulation on peripheral sympathetic nerve fibers. In contrast, the antihypertensive effects of i.c.m. pergolide would appear to be mediated by both alpha-2 adrenoceptors and DA-2 dopamine receptors located within the central nervous system.

SummaryThe rationale for the use of a narrow-spectrum antibiotic such as erythromycin is reviewed and the results are reported of the use of erythromycin lactobionate, 2 g daily given by intravenous infusion for 5 days, in 17 patients with acute exacerbations of chronic bronchitis. Thirteen of the patients showed an excellent response to treatment, as assessed by clinical and radiological findings, although the results were not always supported by the bacteriological data. Gram-negative bacilli were isolated from the sputum of all 4 patients who failed to respond to erythromycin, and 3 were subsequently treated successfully when antibiotic therapy was changed.

SummaryA study was carried out to investigate the pharmacokinetic parameters of erythromycin lactobionate and erythromycin ethylsuccinate in patients with acute exacerbation of chronic bronchitis. Erythromycin concentrations in serum and sputum were determined after 1 g oral doses of the ethylsuccinate and after a 500 mg intravenous injection of the lactobionate. Models of the doses and regimens were simulated from the data. The results demonstrated the fast diffusion of erythromycin lactobionate in the peripheral compartment. Plasma and bronchial secretion concentrations of the two products were particularly high, especially in the case of the lactobionate which, therefore, is indicated in the most severe infections.

In pentobarbital-anesthetized dogs with decentralized adrenal glands, sinoaortic baroreceptor deafferentation produced an increase in mean aortic blood pressure which reached a maximum (42 +/- 5 mm Hg, n = 6) within 5 min and then waned entirely within the subsequent 25 min. In contrast, in sham-operated dogs, the maximal pressor response due to deafferentation was of greater magnitude (63 +/- 6 mm Hg, n = 8) and of much longer duration (44 +/- 4 mm Hg, 60 min after deafferentation). Heart rate was only augmented slightly in both preparations. A marked elevation of epinephrine plasma concentration occurred 5 min after deafferentation and the magnitude of this effect was 8 times greater in dogs with innervated than denervated adrenal glands. Norepinephrine plasma concentration increased moderately and similarly in the two preparations. Administration of pergolide (30.0 micrograms/kg i.v.) 15 min before undertaking the deafferentation procedure induced a small, short-lasting increase in blood pressure and a small fall in heart rate in dogs in which the innervation to the adrenal glands was left either intact (sham-operated) or removed surgically. In dogs with adrenal gland denervated, pergolide blocked entirely the pressor response and the small elevation in plasma concentration of catecholamines evoked by sinoaortic deafferentation in the matched, saline-pretreated group. However, in sham-operated dogs (intact adrenal innervation), pergolide reduced partially (by 41%) the increase in blood pressure and plasma epinephrine concentration caused by deafferentation. The decrease in heart rate, produced by pergolide, was abolished by deafferentation in sham-operated and adrenal decentralized dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

In conscious spontaneously hypertensive rats, pergolide (50.0 micrograms/kg s.c.) produced a sustained decrease in tail artery pressure which was blocked by haloperidol (1.0 mg/kg s.c.) pretreatment. In anesthetized spontaneously hypertensive rats this effect was accompanied by a fall in total peripheral resistance inasmuch as pergolide did not significantly change cardiac output. In anesthetized normotensive rats, pergolide (30.0 micrograms/kg i.v.) also lowered blood pressure. This effect was not significantly modified by adrenalectomy, methysergide, idazoxan (alpha-2 adrenoceptor antagonist), vagotomy alone or plus ligation of carotid arteries or plus atenolol, but was entirely prevented by domperidone or sulpiride pretreatment and was reverted to a pressor response (due to stimulation of alpha adrenoceptors and 5-hydroxytryptamine receptors) by blockade of ganglionic transmission with chlorisondamine. Pergolide given either i.v. or into the cisterna magna or the lateral cerebral ventricle produced changes in blood pressure of the same magnitude. In intact or adrenalectomized rats, i.v. pergolide significantly lowered plasma norepinephrine concentration. Furthermore, in saline but not sulpiride-pretreated pithed rats, pergolide reduced the pressor responses and the accompanying increases in plasma norepinephrine evoked by electrical stimulation of the spinal cord. However, pergolide failed to modify the vascular reactivity to several pressor agents and lacked beta-2 and DA-1 dopamine receptor agonist properties. These results indicate that the decrease in blood pressure produced by pergolide can be accounted for by an inhibition of sympathetic tone resulting from stimulation of peripheral neuronal dopamine receptors. A possible central contribution remains to be substantiated. The pronounced bradycardia produced by pergolide (30.0 micrograms/kg i.v.) in anesthetized intact rats was partly reduced by vagotomy, methylatropine, domperidone, sulpiride, idazoxan, phentolamine or atenolol. The effects of pergolide in vagotomized rats were further diminished by domperidone but they were blocked by the combination of phentolamine or idazoxan plus domperidone. In rats pretreated with atenolol or in rats with the cervical section of spinal cord and the low level of heart rate increased with an isoprenaline infusion, the decrease in heart rate produced by pergolide was abolished by domperidone, methylatropine or idazoxan. In pithed rats, pergolide changed neither the base-line heart rate nor the tachycardia to exogenous norepinephrine nor the bradycardia evoked by carbachol or electrical stimulation of the peripheral cervical vagus.(ABSTRACT TRUNCATED AT 400 WORDS)