The adrenergic status was studied through evaluation of platelet alpha 2-adrenoceptor number [( 3H]yohimbine binding sites), plasma catecholamine levels and blood pressure response to noradrenaline infusion in three groups of subjects (1) Parkinsonians with orthostatic hypotension; (2) Parkinsonians without orthostatic hypotension; and (3) control subjects. In Parkinsonians with orthostatic hypotension, systolic and diastolic blood pressures significantly (P less than 0.05) decreased from 144 +/- 9 and 76 +/- 6 mmHg in the lying position to 95 +/- 12 and 60 +/- 7 mmHg after 5 min standing. In these patients, noradrenaline plasma levels were significantly low (62 +/- 11 pg ml-1, (P less than 0.05) when compared with controls (219 +/- 13 pg ml-1) whereas no difference was noticed in Parkinsonians without orthostatic hypotension (195 +/- 14 pg ml-1). The noradrenaline dose required for a 25 mmHg increase in systolic blood pressure was significantly (P less than 0.01) lower in Parkinsonians with orthostatic hypotension (0.19 +/- 0.03 microgram kg-1) when compared with Parkinsonians without orthostatic hypotension (0.86 +/- 0.11 microgram kg-1) or with controls (0.68 +/- 0.1 microgram kg-1). Platelet alpha 2-adrenoceptor number was higher in Parkinsonians with orthostatic hypotension (313 +/- 52 fmol mg-1 protein) than in Parkinsonians without orthostatic hypotension (168 +/- 9 fmol mg-1 protein) or in controls (175 +/- 4 fmol mg-1 protein) with no change in Kd. This study demonstrates that in patients with Parkinson's disease, orthostatic hypotension is associated with an increase in both vascular sensitivity to noradrenaline and platelet alpha 2-adrenoceptor number.(ABSTRACT TRUNCATED AT 250 WORDS)
1 The effects of yohimbine (0.5mg kg-i.v.) on both resting and parasympathetic and sympathetic stimulation-induced submaxillary salivary responses were investigated in the anaesthetized dog. 2 Salivary secretion was increased significantly for a period of 45min following an injection of yohimbine. 3 Sectioning of the chorda tympani (but not the cervical sympathetic) nerve abolished the yohimbine-induced increase in resting salivary secretion and potentiated that elicited by electrical stimulation of the chorda tympani nerve. 4 These results show that yohimbine increases submaxillary secretion by inhibition of presynaptic a2-adrenoceptors located on the chorda tympani, which inhibit cholinergic transmission.
1 Lipid mobilization during a hypocaloric diet may be enhanced by a pharmacological approach using a2-adrenoceptor antagonists since these drugs are known to increase sympathetic tone and stimulate lipolysis. Studies were undertaken in the dog in order to evaluate the effects of oral yohimbine administration (a2-adrenoceptor antagonist) on heat production, metabolic, endocrinological and cardiovascular parameters.2 Acute oral yohimbine (0.25 or 0.40mg kg ')provoked an increase in plasma non-esterfied fatty acids. The drug increased sympathetic nervous system activity as indicated by the increased level of plasma noradrenaline. These effects persisted during the entire experimental period (4 h). The increase in plasma noradrenaline level was two fold higher with the higher dose of yohimbine (0.4mgkg-1). The plasma adrenaline level was increased only with the higher dose. 3 Yohimbine transiently increased plasma insulin and the effect was dose-dependent. 4 Yohimbine (0.25mg kg-1) enhanced heart rate and arterial blood pressure. 5 The effect of yohimbine on oxygen consumption, carbon dioxide and heat production was determined by indirect calorimetry. The drug (0.25 mg kg-1) increased°2 consumption and CO2 and heat production 30min after its administration and the effect persisted over the experimental period. The respiratory quotient, rather low in the fasting animals, remained unchanged. 6 The present work indicates that thermogenesis and lipid mobilization are enhanced during fasting in the dog by a2-adrenoceptor blockade. Yohimbine also induced a transient increase in plasma insulin level and increased heart rate and blood pressure. The lipid mobilization plus the action on thermogenesis observed after yohimbine draw attention to the putative interest of a2-antagonists in the pharmacological treatment of obesity during restricted calorie intake.
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