title: Comparison of blood pressure and angiotensin responses to the renin inhibitor Ro 42-5892 and the angiotensin converting enzyme inhibitor enalapril in essential hypertension.
abstract: OBJECTIVE
  To compare the responses of angiotensin II (Ang II) and blood pressure to the renin inhibitor Ro 42-5892 and the angiotensin converting enzyme (ACE) inhibitor enalapril.
  
  
  METHODS
  Eight non-sodium-restricted patients with mild-to-moderate essential hypertension.
  
  
  METHODS
  A single-blind crossover study. Ro 42-5892 (600 mg orally, once a day) and enalapril (20 mg orally, once a day) were given for 8 days before detailed investigations were carried out.
  
  
  METHODS
  Ambulatory blood pressure was measured directly for 24 h by the Oxford technique on three occasions. Off-treatment and on day 8 of treatment with Ro 42-5892 and with enalapril. Ang II was measured by radioimmunoassay after separation by high-performance liquid chromatography.
  
  
  RESULTS
  Plasma renin activity and Ang II were lowered by 83% [95% confidence interval (CI) 61-105] and 68% (95% CI 49-87), respectively, 0.5-1 h after Ro 42-5892, but after only 3 h values had returned to baseline. Unlike this rapid and short-term suppression of Ang II, the maximal antihypertensive response to Ro 42-5892 (fall in blood pressure 12.9/9.0 mmHg) occurred only after 6 h. Blood pressure returned to baseline after 8 h. In response to enalapril, Ang II was maximally suppressed by 63% (95% CI 32-94) after 2 h and by 83% (95% CI 76-90) after 8 h. Despite early maximal Ang II suppression, the maximal antihypertensive response to enalapril occurred only after 12 h (fall in blood pressure 25.3/16.3 mmHg). With this compound a significant antihypertensive effect was still present 24 h after dosing.
  
  
  CONCLUSIONS
  Compared with enalapril at 20 mg once a day, repeated oral administration of a single dose of Ro 42-5892 at 600 mg caused only short-term suppression of Ang II and blood pressure. Suppression of Ang II and reduction in blood pressure were temporally dissociated, both with the ACE inhibitor and the renin inhibitor. This implies that the blood pressure lowering effect of these inhibitors is caused partly by Ang II suppression outside the circulation.
authors.affiliation: Department of Internal Medicine I, University Hospital Dijkzigt, Rotterdam, The Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: van den Meiracker
authors.forename: P J
authors.initials: PJ
authors.lastname: Admiraal
authors.forename: F H
authors.initials: FH
authors.lastname: Derkx
authors.forename: C
authors.initials: C
authors.lastname: Kleinbloesem
authors.forename: A J
authors.initials: AJ
authors.lastname: Man in 't Veld
authors.forename: P
authors.initials: P
authors.lastname: van Brummelen
authors.forename: P
authors.initials: P
authors.lastname: Mulder
authors.forename: M A
authors.initials: MA
authors.lastname: Schalekamp
mesh_terms: D000328:Adult; D000450:Aldosterone / Q000097:blood; D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D012083:Renin / Q000097:blood; D000092502:Renin Inhibitors
chemical_list: D000450:Aldosterone; D000803:Angiotensin I; D000804:Angiotensin II; D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D007093:Imidazoles; D012083:Renin; D000092502:Renin Inhibitors; C065581:remikiren