Effect of rosmarinic acid on the arterial blood pressure in normotensive and hypertensive rats: Role of ACE

Phytomedicine. 2018 Jan 1:38:158-165. doi: 10.1016/j.phymed.2017.02.006. Epub 2017 Feb 24.


Background: In recent years, it has been demonstrated the inhibitory effect of some plant species on the angiotensin-converting enzyme and rosmarinic acid is a prominent constituent of these species.

Hypothesis/purpose: This study was carried out to verify the effect of rosmarinic acid on blood pressure through inhibitory activity on angiotensin-converting enzyme in rats.

Study design: The arterial hypertension was promoted using 2-kidneys 1-clip model in rats. The potential inhibitory rosmarinic acid effect on angiotensin-converting enzyme activity was compared with captopril actions by analyzing in vivo blood pressure dose-response curves to angiotensin I and bradykinin. The in vitro plasma angiotensin-converting enzyme activity was measured by fluorimetry using the substrate Abz-FRK(Dnp)P-OH substrate. In addition, dosages of nitrite/nítrate analysis were carried out.

Results: (1) rosmarinic acid caused systolic blood pressure dose-dependent decrease in hypertensive rats; (2) The angiotensin I dose-response curves demonstrated that rosmarinic acid promotes minor changes in systolic blood pressure only in the hypertensive group; (3) The bradykinin dose-response curves showed that both rosmarinic acid and captopril promoted a systolic blood pressure reduction, but only the captopril effect was significant; (4) The angiotensin-converting enzyme activity in rat lung tissue was inhibited by the rosmarinic acid in a dose dependent manner; (5) The analysis of nitrite/nítrate plasma concentrations showed no significant difference among the experimental groups.

Conclusion: The rosmarinic acid is effective in reducing blood pressure, selectively, only in hypertensive animals. The rosmarinic acid (173µM) promoted almost a 98.96% reduction on angiotensin-converting enzyme activity.

Keywords: Angiotensin-converting enzyme; Angiotensin-converting enzyme inhibitors; Captopril; Hypertension; Rosmarinic acid.

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Animals
  • Antihypertensive Agents / pharmacology
  • Blood Pressure / drug effects*
  • Bradykinin / pharmacology
  • Captopril / pharmacology
  • Cinnamates / pharmacology*
  • Depsides / pharmacology*
  • Dose-Response Relationship, Drug
  • Hypertension / drug therapy*
  • Lung / drug effects
  • Lung / metabolism
  • Male
  • Peptidyl-Dipeptidase A / metabolism
  • Rats, Wistar
  • Rosmarinic Acid


  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Cinnamates
  • Depsides
  • Captopril
  • Peptidyl-Dipeptidase A
  • Bradykinin