Similarity and dissimilarity between angiotensin A and angiotensin II in cardiovascular functions in a rat model

Angiotensin (Ang) A differs from Ang II in a single N-terminal alanine residue. The aim of this study was to investigate whether the effects of Ang A on postischemic cardiac injury and hemodynamics differ from Ang II. After euthanizing Sprague-Dawley rats, hearts were perfused with Krebs-Henseleit buffer for a 20 min preischemic period with or without Ang A or Ang II, followed by 20 min global ischemia and 50 min reperfusion. The blood pressure was measured in anesthetized rats. Ang A (0.1, 1.0, 10 μg/kg) deteriorated the postischemic left ventricular hemodynamics in a dose-dependent manner, which was similar to that by Ang II. Ang A (10 μg/kg) increased the infarct size and the lactate dehydrogenase level, and decreased the coronary flow, which were attenuated by the pretreatment with Ang type 1 receptor (AT₁R) antagonist (losartan) but not by AT₂R antagonist (PD123319). Ang A increased the expression of apoptotic proteins and decreased the expression of antioxidative proteins. Interestingly, Ang A increased the atrial natriuretic peptide (ANP) level in coronary effluent and in atrial perfusate but Ang II did not increase it. Ang A increased mean arterial blood pressure, which was less potent than Ang II. These results suggest that Ang A has a similar effect on postischemic injury via AT₁R and less potent vasopressor effect but opposite effect on ANP secretion as compared to Ang II.