Angiotensin-(1–7) Is a Modulator of the Human Renin-Angiotensin System
- 1 August 1999
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hypertension
- Vol. 34 (2), 296-301
- https://doi.org/10.1161/01.hyp.34.2.296
Abstract
Abstract —The renin-angiotensin system is important for cardiovascular homeostasis. Currently, therapies for different cardiovascular diseases are based on inhibition of angiotensin-converting enzyme (ACE) or angiotensin II receptor blockade. Inhibition of ACE blocks metabolism of angiotensin-(1–7) to angiotensin-(1–5) and can lead to elevation of angiotensin-(1–7) levels in plasma and tissue. In animal models, angiotensin-(1–7) itself causes or enhances vasodilation and inhibits vascular contractions to angiotensin II. The function of angiotensin-(1–5) is unknown. We investigated whether angiotensin-(1–7) and angiotensin-(1–5) inhibit ACE or antagonize angiotensin-induced vasoconstrictions in humans. ACE activity in plasma and atrial tissue was inhibited by angiotensin-(1–7) up to 100%, with an IC 50 of 3.0 and 4.0 μmol/L, respectively. In human internal mammary arteries, contractions induced by angiotensin I and II and the non–ACE-specific substrate [Pro 11 ,D-Ala 12 ]-angiotensin I were antagonized by angiotensin-(1–7) (10 −5 mol/L) in a noncompetitive way, with a 60% inhibition of the maximal response to angiotensin II. Contractions to ACE-specific substrate [Pro 10 ]-angiotensin I were also inhibited, an effect only partly accounted for by antagonism of angiotensin II. Angiotensin-(1–5) inhibited plasma ACE activity with a potency equal to that of angiotensin I but had no effect on arterial contractions. In conclusion, angiotensin-(1–7) blocks angiotensin II–induced vasoconstriction and inhibits ACE in human cardiovascular tissues. Angiotensin-(1–5) only inhibits ACE. These results show that angiotensin-(1–7) may be an important modulator of the human renin-angiotensin system.Keywords
This publication has 10 references indexed in Scilit:
- Characterization of angiotensin-(1-7) in the urine of normal and essential hypertensive subjects.American Journal of Hypertension, 1998
- Angiotensin-(1-7) and the Rat Aorta: Modulation by the EndotheliumJournal of Cardiovascular Pharmacology, 1997
- Effects of captopril related to increased levels of prostacyclin and angiotensin-(1-7) in essential hypertensionJournal of Hypertension, 1996
- Vasoconstrictor action of angiotensin I-convertase and the synthetic substrate (Pro11,D-Ala12)-angiotensin I.Hypertension, 1994
- Effects of converting enzyme inhibitors on angiotensin and bradykinin peptides.Hypertension, 1994
- Angiotensin-converting enzyme inhibition improves cardiac function. Role of bradykinin.Hypertension, 1994
- Release of nitric oxide by angiotensin‐(1–7) from porcine coronary endothelium: implications for a novel angiotensin receptorBritish Journal of Pharmacology, 1994
- Angiotensin-(1-7). A member of circulating angiotensin peptides.Hypertension, 1991
- Biological activities of angiotensin II-(1–6)-hexapeptide and angiotensin II-(1–7)-heptapeptide in manLife Sciences, 1986
- Spectrophotometric assay and properties of the angiotensin-converting enzyme of rabbit lungBiochemical Pharmacology, 1971