title: Effects of captopril related to increased levels of prostacyclin and angiotensin-(1-7) in essential hypertension.
abstract: OBJECTIVE
  To evaluate the contribution of angiotensin-(1-7) [Ang-(1-7)] and prostaglandins to the acute and long-term antihypertensive actions of captopril in mild-to-moderate essential hypertensive patients.
  
  
  METHODS
  Blood pressure, cardiac rate and the plasma concentrations of angiotensin I (Ang I), angiotensin II (Ang II), Ang-(1-7), prostaglandin E2 and 6-keto prostaglandin F1 alpha (the breakdown product of prostacyclin) were determined in the peripheral venous blood of 24 essential hypertensive subjects before and 3 h after administration of 50 mg captopril. Eleven of 24 patients completed a 6-month treatment period with captopril monotherapy (50 mg twice a day). The hemodynamic and hormonal response produced by a last 50 mg dose of captopril was determined once again in the 11 subjects who maintained blood pressure control with captopril monotherapy for 6 months.
  
  
  RESULTS
  The fall in blood pressure produced 3 h after drug intake was comparable for the first and the last 50 mg captopril dose. Although the first response to captopril increased plasma levels of Ang I only, the response to the last dose of the drug (6 months after) caused significantly higher levels of Ang I and Ang-(1-7). Neither acute nor chronic therapy with captopril had a significant effect on plasma concentrations of Ang II. Although plasma levels of prostaglandin E2 and 6-keto prostaglandin F1 alpha were not modified by a first exposure to captopril, the concentrations of 6-keto prostaglandin F1 alpha but not prostaglandin E2 rose significantly in subjects treated with the inhibitor for 6 months. A negative correlation was also demonstrated between diastolic blood pressure and plasma Ang-(1-7) levels in the 11 essential hypertensive subjects in whom blood pressure was controlled with captopril monotherapy.
  
  
  CONCLUSIONS
  Inhibition of angiotensin converting enzyme with captopril had a significant effect on blood pressure that was not directly accounted for by a suppression of plasma Ang II levels. Continuous therapy with captopril unmasked a contribution of Ang-(1-7) and prostacyclin to the antihypertensive actions of this drug.
authors.affiliation: Hypertension Unit, San Carlos University Hospital, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Luque
authors.forename: P
authors.initials: P
authors.lastname: Martin
authors.forename: N
authors.initials: N
authors.lastname: Martell
authors.forename: C
authors.initials: C
authors.lastname: Fernandez
authors.forename: K B
authors.initials: KB
authors.lastname: Brosnihan
authors.forename: C M
authors.initials: CM
authors.lastname: Ferrario
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000803:Angiotensin I; D000804:Angiotensin II / Q000097:blood*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002216:Captopril / Q000627:therapeutic use*; D011464:Epoprostenol / Q000097:blood*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D011464:Epoprostenol; C118790:angiotensin I (1-7)