The cardiovascular influence of interleukin-1 beta on the expression of bradykinin B1 and B2 receptors.

ABSTRACT

The cytokine interleukin 1ss (IL-1ss) and the bradykinin receptors 1 (B1R) and 2 (B2R) are known to be upregulated in the ischemic heart. In the present study we investigated whether or not there is a causal link between these entities. Further we investigated whether or not pharmacological inhibition of IL-1ss release affects B1R and B2R regulation as well as left ventricular (LV) function in an in vivo rat model of myocardial infarction (MI). B1R and B2R mRNA levels were determined in cultured rat cardiomyocytes, aortic smooth muscle cells and cardiac fibroblasts (n=6 per group) under basal conditions, and after incubation of IL-1ss (40, 400 and 4000 pg/ml). Also, MI was induced in male Sprague-Dawley rats by ligation of the left descending coronary artery. Rats were treated with the interleukin converting enzyme inhibitor (ICEI) pralnacasan (50 mg/kg/day), or with a placebo. Three weeks after induction of MI, LV function was assessed using a 1.4 Millar TIP-catheter. Cardiac expressions of B1R and B2R mRNA were measured using ribonuclease-protection assays. Under basal conditions, both B1R and B2R were expressed in cardiomyocytes and smooth muscle cells, but not in cardiac fibroblasts. IL-1ss cultivation led only in cardiomyocytes to a significant upregulation of B1R mRNA. To a significant upregulation of B2R mRNA, it did not. In addition, ICEI treatment led in vivo to a significant downregulation of cardiac B1R mRNA, but not of B2R mRNA expression three weeks after induction of MI. Our data suggest that a causal link exists between cardiac IL-1ss content and B1R regulation after MI.