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  • Title: Comparative effects of clonidine and dihydroergotamine on venomotor tone and orthostatic tolerance in patients with severe hypoadrenergic orthostatic hypotension.
    Author: Victor RG, Talman WT.
    Journal: Am J Med; 2002 Apr 01; 112(5):361-8. PubMed ID: 11904110.
    Abstract:
    PURPOSE: Clonidine, an alpha(2)-adrenergic agonist, raises blood pressure in patients with autonomic failure, in whom failure of reflex neurogenic venoconstriction leads to severe orthostatic hypotension. Because animal studies suggest that postjunctional alpha(2)-adrenoreceptors are located mainly on venous capacitance rather than arterial resistance vessels, we tested the hypothesis that venoconstriction is the main mechanism by which clonidine raises blood pressure in patients with autonomic failure. SUBJECTS AND METHODS: We measured forearm venous and arterial tone using plethysmography in 4 patients with autonomic failure before and after acute administration of clonidine (0.4 mg orally) or dihydroergotamine (0.15 mg intravenously), a known venoconstrictor agent. We also recorded supine intraarterial pressure at rest and during graded orthostatic stress with lower body negative pressure. RESULTS: Clonidine and dihydroergotamine caused similar increases in supine (mean +/- SD) arterial pressure (+23 +/- 11 mm Hg vs. and +27 +/- 5 mm Hg) and forearm vascular resistance (+36% +/- 13% vs. +28% +/- 9%). However, the drugs had different effects on forearm venous tone, which increased by 38% +/- 9% with dihydroergotamine (P = 0.01 vs. control) but was unaffected by clonidine (change = 0% +/- 14%). A single dose of clonidine was less effective than a single dose of dihydroergotamine in maintaining arterial pressure during graded orthostatic stress. CONCLUSION: In contrast with what has been hypothesized, clonidine appears to function mainly as an arterial constrictor in patients with hypoadrenergic orthostatic hypotension. Further studies are needed to determine if venoconstrictor agents are of greater therapeutic benefit in this condition than are pure arterial vasoconstrictors.
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