Angiotensin-(1-7): Pharmacological properties and pharmacotherapeutic perspectives

Dilek Iusuf, Robert H. Henning, Wiek H. van Gilst, Anton J. M. Roks*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

103 Citations (Scopus)

Abstract

Therapeutic modulation of the renin-angiotensin system is not complete without taking into consideration the beneficial effects of angiotensin-(1-7) in cardiovascular pathology. Various pharmacological pathways are already exploited to involve this heptapeptide in therapy as both inhibitors of angiotensin-converting enzyme and angiotensin II type 1 receptor blockers increase its levels. These drugs and administered angiotensin-(1-7) elicit various common effects, and some effects of the drugs are partially mediated by angiotensin-(1-7). The pharmacodynamic profile of angiotensin-(1-7) is rather complex, and in vitro and in vivo studies demonstrated a wide palette of effects for angiotensin-(1-7), some of them potentially beneficial for cardiovascular disease. Using various animal models to study cardiovascular physiology and disease it was shown that angiotensin-(1-7) has antihypertensive, antihypertrophic, antifibrotic and antithrombotic properties, all properties that may prove beneficial in a clinical setting. We also observed a novel action of angiotensin-(1-7), namely its capacity to stimulate the proliferation of endothelial progenitor cells. Access of angiotensin-(1-7) to the clinic, however, is restricted due to its unfavorable pharmacokinetic properties. In order to benefit of the therapeutic potential of angiotensin-(1-7) it is crucial to increase its half-life, either by using more stable analogues, which are now under development, or specific delivery methods. We here review the pharmacological characteristics and therapeutic potential of angiotensin-(l-7), implementing the experimental strategies taken to exploit the pharmacological mechanism of this heptapeptide in a clinical setting, and present our contribution to this field of research. (C) 2008 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)303-312
Number of pages10
JournalEuropean Journal of Pharmacology
Volume585
Issue number2-3
DOIs
Publication statusPublished - 13-May-2008

Keywords

  • angiotensin-(1-7)
  • Mas receptor
  • cardiovascular disease
  • angiotensin-converting enzyme inhibitor
  • angiotensin II type 1 receptor blocker
  • NITRIC-OXIDE SYNTHASE
  • CONVERTING-ENZYME-INHIBITION
  • SPONTANEOUSLY HYPERTENSIVE-RATS
  • VASCULAR SMOOTH-MUSCLE
  • EFFECTIVE RENIN INHIBITOR
  • CHRONIC HEART-FAILURE
  • COUPLED-RECEPTOR MAS
  • PROTEIN-KINASE-C
  • BLOOD-PRESSURE
  • ENDOTHELIAL FUNCTION

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