Angiotensin-(1-7): pharmacological properties and pharmacotherapeutic perspectives.
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-(1-7), 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.
Iusuf
Dilek
D
Department of Clinical Pharmacology, University Medical Center Groningen, University of Groningen, The Netherlands.
Henning
Robert H
RH
van Gilst
Wiek H
WH
Roks
Anton J M
AJ
D000803:Angiotensin I / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000187:drug effects; D003920:Diabetes Mellitus / Q000188:drug therapy; D006331:Heart Diseases / Q000188:drug therapy; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D010446:Peptide Fragments / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D012084:Renin-Angiotensin System / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
D000959:Antihypertensive Agents; D010446:Peptide Fragments; D000803:Angiotensin I; C118790:angiotensin I (1-7)