Effects of Angiotensin-Converting Enzyme Inhibition and Alpha 1-Adrenergic Receptor Blockade on Inflammation and Hemostasis in Human Hypertension

J Cardiovasc Pharmacol. 2018 Apr;71(4):240-247. doi: 10.1097/FJC.0000000000000565.

Abstract

Drugs blocking the renin-angiotensin-aldosterone system may offer benefit on endothelial function, inflammation, and hemostasis in addition to the effects of reducing blood pressure. We examined the contribution of the angiotensin-converting enzyme inhibitor ramipril and the alpha 1-adrenergic receptor blocker doxazosin on blood pressure and on markers of inflammation and hemostasis in 59 individuals with mild-to-moderate hypertension randomized to receive double-blind ramipril 10 mg od or doxazosin 8 mg od for 12 weeks. Inflammatory markers (interleukin-6, soluble interleukin-6 receptor, interleukin-8, tumor necrosis factor-α, monocyte chemoattractant protein-1, and C-reactive protein) and hemostasis (plasminogen activator inhibitor-1 activity, tissue plasminogen activator antigen, thrombin-antithrombin complex, and thrombin generation by calibrated automated thrombogram) were assessed. The treatment reduced blood pressure in both groups. Thrombin-antithrombin complex decreased by treatment, and this was dependent on a reduction in thrombin-antithrombin complex in the ramipril group alone. There were no changes in plasminogen activator inhibitor-1 activity, whereas tissue plasminogen activator antigen increased by ramipril and decreased by doxazosin. Only minor changes were observed in systemic inflammation by treatment. Treatment with ramipril seems to reduce thrombin generation beyond effects on reducing blood pressure. Drugs blocking the renin-angiotensin-aldosterone system may reduce atherothrombotic complications beyond their effects to reduce blood pressure.

Trial registration: ClinicalTrials.gov NCT02901977.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists / adverse effects
  • Adrenergic alpha-1 Receptor Antagonists / therapeutic use*
  • Adult
  • Aged
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Biomarkers / blood
  • Blood Pressure / drug effects*
  • Double-Blind Method
  • Doxazosin / adverse effects
  • Doxazosin / therapeutic use*
  • Female
  • Hemostasis / drug effects*
  • Humans
  • Hypertension / blood
  • Hypertension / diagnosis
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Inflammation / blood
  • Inflammation / diagnosis
  • Inflammation / drug therapy*
  • Inflammation / physiopathology
  • Inflammation Mediators / blood
  • Male
  • Middle Aged
  • Ramipril / adverse effects
  • Ramipril / therapeutic use*
  • Renin-Angiotensin System / drug effects*
  • Sweden
  • Time Factors
  • Treatment Outcome

Substances

  • Adrenergic alpha-1 Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Biomarkers
  • Inflammation Mediators
  • Ramipril
  • Doxazosin

Associated data

  • EudraCT/2007-000631-25
  • ClinicalTrials.gov/NCT02901977