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Cardiac interstitial bradykinin release during ischemia is enhanced by ischemic preconditioning. Am J Physiol Heart Circ Physiol 279: H116-H121, 2000.--Ischemic preconditioning is known to protect the myocardium from ischemia-reperfusion injury. We examined the transmural release of bradykinin during myocardial ischemia and the influence of ischemic preconditioning on bradykinin release during subsequent myocardial ischemia. Myocardial ischemia was induced by occlusion of the left anterior descending coronary artery in anesthetized cats. Cardiac microdialysis was performed by implantation and perfusion of dialysis probes in the epicardium and endocardium. In eight animals, bradykinin release was greater in the endocardium than in the epicardium (14.4 [+ or -] 2.8 vs. 7.3 [+ or -] 1.7 ng/ml, P [is less than] 0.05) during 30 min of ischemia. In seven animals subjected to preconditioning, myocardial bradykinin release was potentiated significantly from 2.4 [+ or -] 0.6 ng/ml during the control period to 23.1 [+ or -] 2.5 ng/ml during 30 min of myocardial ischemia compared with the non-preconditioning group (from 2.7 [+ or -] 0.6 to 13.4 [+ or -] 1.9 ng/ml, P [is less than] 0.05, n = 6). Thus this study provides further evidence that transmural gradients of bradykinin are produced during ischemia. The results also suggest that ischemic preconditioning enhances bradykinin release in the myocardial interstitial fluid during subsequent ischemia, which is likely one of the mechanisms of cardioprotection of ischemic preconditioning. cardiac microdialysis; angiotensin-converting enzyme inhibitors; captopril; kinin receptors; myocardium

Liu, Yun-He, Xiao-Ping Yang, Dharmesh Mehta, Manohar Bulagannawar, Gloria M. Scicli, and Oscar A. Carretero. Role of kinins in chronic heart failure and in the therapeutic effect of ACE inhibitors in kininogen-deficient rats. Am. J. Physiol. Heart Circ. Physiol. 278: H507-H514, 2000.--Using Brown Norway Katholiek (BNK) rats, which are deficient in kininogen (kinin precursor) due to a mutation in the kininogen gene, we examined the role of endogenous kinins in 1) normal cardiac function; 2) myocardial infarction (MI) caused by coronary artery ligation; 3) cardiac remodeling in the development of heart failure (HF) after MI; and 4) the cardioprotective effect of angiotensin-converting enzyme inhibitors (ACED on HF after MI. Two months after MI, rats were randomly treated with vehicle or the ACEI ramipril for 2 mo. Brown Norway rats (BN), which have normal kininogen, were used as controls. Left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV), end-diastolic pressure (EDP), and ejection fraction (EF) as well as myocardial infarct size (IS), interstitial collagen fraction (ICF), cardiomyocyte cross-sectional area (MCA), and oxygen diffusion distance (ODD) were measured. We found that 1) cardiac hemodynamics, function, and histology were the same in sham-ligated BN and BNK rats; 2) IS was similar in BN anti BNK; 3) in rats with HF treated with vehicle, the decrease in LVEF and the increase in LVEDV, LVESV, LVEDP, ICF, MCA, and ODD did not differ between BNK and BN; and 4) ACEI increased EF, decreased LVEDV and LVESV, and improved cardiac remodeling in BN-HF rats, and these effects were partially blocked by the bradykinin [B.sub.2] receptor antagonist icatibant (HOE-140). In BNK-HF rats, ACEI failed to produce these beneficial cardiac effects. We concluded that in rats. lack of kinins does not influence regulation of normal cardiac function, myocardial infarct size, or development of HF; however, kinins appear to play an important role in the cardioprotective effect of ACEI, since 1) this effect was significantly diminished in kininogen-deficient rats and 2) it was blocked by a [B2] kinin receptor antagonist in BN rats. Brown Norway Katholiek rats; myocardial infarction; heart failure