Impact of kinins in the treatment of cardiovascular diseases

Pharmacol Ther. 2012 Jul;135(1):94-111. doi: 10.1016/j.pharmthera.2012.04.002. Epub 2012 Apr 17.

Abstract

In recent years, ACE Inhibitors (ACEIs) and Angiotensin II receptor antagonists (also known as AT1 receptor antagonists (AT1-RAs), angiotensin receptor blockers (ARBs), or Sartans), have become the drugs of choice for the treatment of hypertension, heart and renal failure, coronary artery diseases, myocardial infarction and diabetes. By suppressing angiotensin and potentiating bradykinin effects, ACEIs and ARBs activate hemodynamic, metabolic and cellular mechanisms that not only reduce high blood pressure, but also protect the endothelium, the heart, the kidney and the brain, namely the target organs which are at risk in cardiovascular diseases. Major therapeutic benefits of these drugs are the reduction of cardiovascular events and the amelioration of the quality of life and of the patient survival. Results from large clinical trials have established that ACEIs and ARBs are efficient and safe drugs, suitable for the chronic treatments of cardiovascular diseases. Side effects are rare and easily manageable in most cases. The following is a brief review of the basic actions and mechanisms by which two opposing systems, the renin-angiotensin (RAS) and the kallikrein-kinin (KKS), interact in the regulation of cardiovascular and fluid homeostasis to keep the balance in healthy life and correct the imbalance in pathological conditions. Here we discuss how and why imbalances created by overactive RAS are best corrected by treatments with ACEI or AT1-RAs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Animals
  • Cardiovascular Agents / therapeutic use*
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / physiopathology
  • Homeostasis
  • Humans
  • Kallikrein-Kinin System / drug effects*
  • Kallikreins / metabolism
  • Kinins / metabolism*
  • Kinins / therapeutic use
  • Practice Guidelines as Topic
  • Receptors, Bradykinin / drug effects
  • Receptors, Bradykinin / metabolism
  • Renin-Angiotensin System / drug effects
  • Signal Transduction / drug effects

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Cardiovascular Agents
  • Kinins
  • Receptors, Bradykinin
  • Kallikreins