title: Comparative effects of clonidine and dihydroergotamine on venomotor tone and orthostatic tolerance in patients with severe hypoadrenergic orthostatic hypotension.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Donald W. Reynolds Clinical Cardiovascular Research Center, Department of Internal Medicine, Hypertension Division, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75235-8586, USA.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Victor
authors.forename: William T
authors.initials: WT
authors.lastname: Talman
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D000368:Aged; D001342:Autonomic Nervous System Diseases / Q000150:complications; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000627:therapeutic use*; D004087:Dihydroergotamine / Q000627:therapeutic use*; D005260:Female; D005542:Forearm; D006801:Humans; D007024:Hypotension, Orthostatic / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D010991:Plethysmography; D014655:Vascular Resistance; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
chemical_list: D000316:Adrenergic alpha-Agonists; D014662:Vasoconstrictor Agents; D004087:Dihydroergotamine; D003000:Clonidine