title: Attenuation by ACE inhibitor drugs of alpha-adrenoceptor sensitivity in human vessels: possible differences related to drug lipophilicity.
abstract: OBJECTIVE
  We investigated the effect of angiotensin converting enzyme inhibitors (ACEIs) on postsynaptic adrenoceptor sensitivity and compared the effect of the lipophilic ACEI, quinapril, and that of hydrophilic agent, enalapril in human vessels.
  
  
  METHODS
  Alpha-adrenoceptor sensitivity was evaluated using the dorsal hand vein compliance technique. The dose-response curves of vasoconstriction to phenylephrine and prostaglandin F2alpha were obtained in healthy male volunteers.
  
  
  RESULTS
  The ACEIs shifted the dose-response curve of phenylephrine to the right and raised the median effective dose (ED50; 189.3 (57.6 ng min(-1)) of phenylephrine. Following quinapril administration, ED50 increased to 481.1 (101.8 ngmin(-1) compared with 266.8 (55.8 ngmin(-1) after enalapril (95% CI for differences; 31.1-397.5 ng min(-1)). Quinapril administration had no effect on the dose-response curve of PGF2alpha.
  
  
  CONCLUSIONS
  ACE inhibition attenuates alpha-adrenoceptor sensitivity in human vessels. The effect of quinapril, a lipophilic ACEI, was greater than that of enalapril, a hydrophilic ACEI. Lipophilic ACEIs may be more potent in vasodilating effect than hydrophilic ACEIs. Angiotensin II concentration in tissue rather than that in plasma may contribute to the alpha-adrenoceptor sensitivity of the vessels.
authors.affiliation: Department of Clinical Pharmacology, Hamamatsu University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Umemura
authors.forename: K
authors.initials: K
authors.lastname: Kosuge
authors.forename: M
authors.initials: M
authors.lastname: Nishimoto
authors.forename: K
authors.initials: K
authors.lastname: Ohashi
authors.forename: M
authors.initials: M
authors.lastname: Nakashima
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism; D002302:Cardiac Output / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D003187:Compliance; D015237:Dinoprost / Q000494:pharmacology; D004656:Enalapril / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D000077583:Quinapril; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D016037:Single-Blind Method; D044005:Tetrahydroisoquinolines; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000317:Adrenergic alpha-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002395:Catecholamines; D007546:Isoquinolines; D011942:Receptors, Adrenergic, alpha; D044005:Tetrahydroisoquinolines; D014665:Vasodilator Agents; D010656:Phenylephrine; D004656:Enalapril; D015237:Dinoprost; D000077583:Quinapril