Abstract
In the rat heart, there is a remarkable remodeling due to catecholamines. As to the functional effects, norepinephrine (NE) induced a marked positive chronotropic effect and an elevation in right ventricular (RV) systolic pressure, while left ventricular (LV) systolic pressure was only slightly affected in rats in vivo at least during the first two weeks of continuous i.v. administration. In the isolated perfused working rat heart, there was an increase in aortic flow and coronary flow and thus in cardiac output during the first 120 minutes of continuous NE administration. NE induced hypertrophy of predominantly the LV as indicated by the elevation in LV weight/body weight ratio and the increase in the expression of the atrial natriuretic peptide. Increased expression of colligin, collagen I and III preceded the histologically determined interstitial fibrosis of the LV. Several metabolic processes were also altered. A characteristic feature was the stimulation of the oxidative pentose phosphate pathway by all catecholamines tested. Both the activity and mRNA of glucose-6-phosphate dehydrogenase, the first and regulating enzyme of this pathway, turned out to be elevated and seemed to be a marker of cardiac hypertrophy. In the isolated perfused working rat heart, NE increased the expression of the proto-oncogenes c-fos and c-myc. Combination of NE with pre- and afterload elevation induced the signals of both proto-oncogenes to appear earlier and to persist for a longer period of time. There was also an increased expression of interleukin (IL)-6 predominantly in the LV in a narrow time window between 4 and 12 hours of continuous NE application. The maximum increase was seen at 4 hours. IL-1β mRNA was also increased/ however, the maximum was at 12 hours. The increase in the RV was much smaller than in the LV. IL-6 and IL-lβ may be involved both in the development of cardiac hypertrophy and fibrosis which both occurred mainly in the LV under the influence of NE and could be prevented by appropriate adrenergic blockade.
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Zimmer, HG. (2003). Catecholamines and Cardiac Remodeling. In: Singal, P.K., Dixon, I.M.C., Kirshenbaum, L.A., Dhalla, N.S. (eds) Cardiac Remodeling and Failure. Progress in Experimental Cardiology, vol 5. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9262-8_20
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DOI: https://doi.org/10.1007/978-1-4419-9262-8_20
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