Cyclooxygenase mediates cardioprotection of angiotensin-(1-7) against ischemia/reperfusion-induced injury through the inhibition of oxidative stress

Abstract

Abstract. Angiotensin (Ang)-(1-7) exhibits cardioprotective effects in myocardial ischemia reperfusion (I/ R)-induced injury. However, the roles of oxidation and cyclooxygenase (COX) in the cardioprotection of Ang-(1-7) remain unclear. This study was conducted to investigate whether oxidation and COX were involved in the cardioprotection of Ang-(1-7) against I/ Rinduced injury in isolated rat hearts. The hearts were subjected to 15 min regional ischemia followed by 30 min reperfusion. Myocardial I/ R treatment induced significant cardiac dysfunction, including ventricular arrhythmia (VA) and a reduction of left ventricular systolic pressure (LVSP), cardiomyocyte apoptosis and oxidative stress, manifesting as an increase in malondialdehyde (MDA) production and a decrease in superoxide dismutase (SOD) activity. Pretreatment of the hearts with 1.0 nmol/ l Ang-(1-7) for 30 min prior to ischemia considerably attenuated I/ R-induced VA, apoptosis and MDA production, and enhanced LVSP and SOD activity. These cardioprotective effects of Ang-(1-7) were antagonized by the intraperitoneal injection of 5 mg/ kg body weight indomethacin (IDM, a COX inhibitor), presenting as an enhancement of VA, apoptosis and MDA production as well as a reduction of LVSP and SOD activity. In conclusion, COX mediated Ang-(1-7)-induced cardioprotection via its antioxidative mechanism.

Angiotensin 1–7 Reduces Mortality and Rupture of Intracranial Aneurysms in Mice

“…Although Cox-2 is generally associated with inflammatory responses, it is also responsible for synthesis of prostacyclin, which is vasoprotective 30 . Protective effects of angiotensin 1-7 in the heart are attenuated by the cyclooxygenase inhibitor, indomethacin 31 . Thus, although Ang-1-7 did not appear to attenuate inflammation in our study, it is possible that some of the protective effects of Ang-1-7 may be mediated by increased synthesis of prostacyclin through the Cox-2 pathway.…”

Multiple pathways are responsible for Anti-inflammatory and Cardiovascular activities of Hordeum vulgare L.

“…Rise in SOD activity are likely to be a consequence of COX inhibition which can up regulates antioxidant enzymes such as SOD [ 38 ]. Similarly COX-2 and GPx are inversely related [ 39 ] and the effect of HV in this case may be related to its ability to inhibit COX. A number of studies show the presence of antioxidant potential of medicinal plants [ 32 , 33 ] including increasing activities of SOD and GPx [ 26 ].…”

The Yin and Yang of ACE/ACE2 Pathways: The Rationale for the Use of Renin-Angiotensin System Inhibitors in COVID-19 Patients

“…Of interest, hypoxia alone or combined with hypercapnia has been shown to significantly increase both plasma renin expression or activity and plasma Ang II expression [61,62]. Moreover, hypercapnic acidosis (pH 6.8/6.9, a condition that could occur in SARS) induced in isolated rat lungs has been shown to induce a (compensatory) venular dilatation mediated by cyclooxygenase activation (inhibited by indomethacin) [63], an enzyme that has been shown to be induced downstream of Ang (1-7)/MasR pathway in isolated rat hearts (again inhibited by indomethacin) [64], suggesting the involvement of ACE2/Ang (1-7) pathway in mediating CO 2 -dependent lung venular vasodilation. Altogether these observations indicate that there is a high probability that hypoxia/hypercapnia, a condition that occurs in SARS patients, might upregulate the activity of both arms of the RAS by suppling high amounts of renin product, Ang I, to ACE and ACE2, which, together, can produce high amounts of Ang II, Ang (1-9), Ang (1-7) and its (ACE-produced) metabolite, Ang (1-5) (see Figure 1).…”