Defective cardiovascular reflexes and supersensitivity to sympathomimetic drugs in autonomic failure.
In 10 patients with chronic autonomic failure the clinical features and cardiovascular reflexes were correlated with the pressor responses to intravenous noradrenaline and tyramine. In all patients there was an exaggerated response to noradrenaline but a normal or only mildly exaggerated response to tyramine. Patients with lack of sinus arrhythmia and by implication baroreceptor reflex loss had greater responsiveness to pressor drugs than patients with preservation of this reflex. The responses to tyramine infusions imply that there must be sufficient noradrenaline released at defective sympathetic endings for a pressor response to occur. However, the lack of rise of plasma noradrenaline following tyramine, except in the patients with pure autonomic failure, clearly separates these responses from those of normal subjects. These results can be explained by the presence of lesions of both central and peripheral sympathetic pathways in patients with chronic autonomic failure and multiple system atrophy or Parkinsonism. The peripheral lesion, which is incomplete, may consist of replication of the receptors so causing supersensitivity with a duration of response that is little prolonged. The peripheral defect in the two patients with pure autonomic failure was found to be more complex and the prolonged response in one of these patients suggests the possibility of defective re-uptake or metabolism of noradrenaline. Clearly further study of the defects of sympathetic endings is required, including the use of other techniques such as catecholamine fluorescence. The extreme supersensitive responses underline the need for blood pressure monitoring during pressor drug studies prior to treatment, if the hazards of recumbent hypertension are to be avoided.
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004402:Dysautonomia, Familial / Q000503:physiopathology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology*; D011311:Pressoreceptors / Q000187:drug effects; D012018:Reflex / Q000187:drug effects*; D014439:Tyramine / Q000494:pharmacology*
D009638:Norepinephrine; D014439:Tyramine