Schunkert, Heribert and Orzechowski, Hans-Dieter and Boecker, Wolfgang and Meier, Reinhard and Riegger, Guenter A. J. and Paul, Martin (1999) The cardiac endothelin system in established pressure overload left ventricular hypertrophy. JOURNAL OF MOLECULAR MEDICINE-JMM, 77 (8). pp. 623-630. ISSN 0946-2716,
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In normal hearts, endothelin-1 (ET-1) has been shown to initiate myocyte growth and to modulate cardiac function. However, regulation of the various components of the system and the functional effects of ET-1 in established left ventricular hypertrophy (LVH) are less clear. We thus studied ET-1, ETA receptor, and endothelin converting enzyme (ECE-1) mRNA regulation as well as the effects of ET-1 on coronary resistance, LV contractility and relaxation in hypertrophied rat hearts. Cardiac pressure overload, secondary to banding of the ascending aorta, resulted in a transient increase of cardiac ET-1 and ETA receptor mRNAs that reached a maximum at 2 days (+75% and +40%, respectively, P<0.05, each). ET-1 mRNA levels reached a second peak at 84 days of pressure overload (+60%, P<0.05), at the later time point in conjunction with elevated ECE-1 mRNA levels (+20%, P<0.05). The functional implications of ET-1 were examined in a study of isolated perfused hearts. Both hearts with established LVH and sham control hearts responded to ET-1 perfusion (10-(11) to 10(-9) M) with an increase of coronary perfusion pressure (CPP; +85+/-15 and +75+/-8 mmHg; P<0.001 each) and a slight decrease of LV systolic pressure (LVP; -12+/-9 and -9+/-7 mmHg; P=NS). In contrast, ET-1 increased LV end-diastolic pressure (LVEDP) only in LVH hearts (+22+/-7 mmHg, P<0.05 versus baseline and +20 +/-7 mmHg, P<0.05 versus sham). Direct stimulation of protein kinase C mimicked the effects of ET-1, whereas inhibition of this kinase or the Na+-H+ exchanger blunted the effects of ET-1 on CPP, LVP, and LVEDP. Interestingly, coadministration of the vasodilator and the nitric oxide (NO) donor nitroglycerin not only prevented the increase of CPP and LVEDP, but also uncovered a slight positive inotropic effect of ET-1 in LVH hearts. Thus, the cardiac expression of ET-1, ETA, and ECE-1 mRNAs displays a distinct pattern during early and advanced cardiac pressure overload. Furthermore, ET-1 mediates a slight depression of systolic, and a profound depression of diastolic, functional parameters in hearts with established LVH, effects that appear to be secondary to ET-1-related coronary vasoconstriction. The data suggest a functional role of the endothelin system in hearts with established pressure overload hypertrophy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CONGESTIVE-HEART-FAILURE; ANGIOTENSIN-CONVERTING ENZYME; RAT-HEART; EXPRESSION; CARDIOMYOCYTES; INDUCTION; GENES; cardiac hypertrophy; endothelin; endothelin converting enzyme; endothelin receptor |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 Jan 2023 13:51 |
| Last Modified: | 11 Jan 2023 13:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/49092 |
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