Changes in levels of angiotensin II and its receptors in a model of inverted stress-induced cardiomyopathy

Abstract

BackgroundStress-induced cardiomyopathy (SIC) has gained increasing attention worldwide and is characterized by extensive ventricular akinesis, Beta-blockers and angiotensin-converting enzyme inhibitors (ACEIs) are the main treatments for SIC patients. The pharmacological mechanism of action of beta-blockers results in the inhibition of the biological effects of catecholamines. However, the mechanism of action of ACEIs in the treatment of cardiomyopathy is not known. Our aim is to assess changes in levels of angiotensin II, angiotensin-II receptors and ACE responses to SIC.MethodsA model of inverted SIC was established in rabbits by vagal electrical stimulation. The serum concentration of angiotensin II and angiotensin (1-7) was detected by enzyme-linked immunosorbent assay. Expression of angiotensin-II receptors was measured by Western blotting and real-time reverse transcription-polymerase chain reaction (RT-PCR), with localization detected by immunofluorescent staining. ACE-II expression in the myocardium was measured by Western blotting.ResultsFrom one day after vagal stimulation, concentrations of angiotensin II were significantly higher in the experimental group than those in the control group (P <0.05). Stress induced a time-dependent decrease in angiotensin subtype-1 (AT1) expression and a time-dependent increase in AT2 expression only in the apical portion of the myocardium. From three days after vagal stimulation, angiotensin (1-7) levels were significantly lower in the experimental group compared with the control group (P <0.05). Expression of the ACE-II protein was significantly downregulated in the experimental group compared with the control group from three days after vagal stimulation (P <0.05).ConclusionsExpression of angiotensin II, its receptors, ACE-II and angiotensin (1-7) was altered in response to SIC. The renin-angiotensin system could represent a therapeutic target in the prevention of SIC.Electronic supplementary materialThe online version of this article (doi:10.1186/s40001-014-0054-8) contains supplementary material, which is available to authorized users.

Neprilysin is a Mediator of Alternative Renin-Angiotensin-System Activation in the Murine and Human Kidney

“…The investigation of the tissue localized RAS is technically challenging, which is reflected by the heterogeneity of reported tissue angiotensin concentrations. The fluctuation of Ang II in plasma ranges over 3 orders of magnitude 23 24 25 while actual physiological levels range between 10 to 100 pg/ml 26 27 28 . To overcome some of the previous technical limitations, we used chemically identical isotope-labelled peptides as internal standards 29 30 for the multiplex liquid chromatography-tandem mass spectrometry (LC-MS/MS) based quantification of 10 angiotensin metabolites in plasma and tissue 27 31 .…”

Angiotensin-(1–7) as a Potential Therapeutic Strategy for Delayed Cerebral Ischemia in Subarachnoid Hemorrhage

“…In a propensity matched cohort, RAS manipulation using ACEi and ARBs, but not beta blockers, gave survival gain at one year and lower recurrence of the TTS ( 164 ). Ang-(1–7) levels were lower than to controls in an animal model of TTS by vagal electrical stimulation ( 165 ). The heart might nevertheless benefit from a higher systemic level of Ang-(1–7), as its levels have been associated with less heart failure after myocardial infarction ( 166 ), less myocardial swelling ( 167 ), and antiarrhythmic effects ( 168 ) ( Figure 3 ).…”