Friedrich, Erik B. and Muders, Frank and Luchner, Andreas and Dietl, Otto and Riegger, Guenter A. J. and Elsner, Dietmar (1999) Contribution of the endothelin system to the renal hypoperfusion associated with experimental congestive heart failure. JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 34 (4). pp. 612-617. ISSN 0160-2446,
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The objective of this study was to define further the local activation of endothelin-1 (ET-1) and the ETA receptor as well as the functional consequences of activated ET-1 for renal hypoperfusion associated with experimental congestive heart failure (CHF). We studied eight rabbits permanently instrumented with Doppler flow probes around the renal arteries before and after the induction of epinephrine-induced CHF. CHF was characterized by left-ventricular dysfunction (fractional shortening 34 +/- 2% vs. 46 +/- 3%; p less than or equal to 0.05) and dilatation (LVEDd 13.6 +/- 0.3 vs. 11.5 +/- 0.4 mm; p less than or equal to 0.05), decreased mean arterial pressure (59.4 +/- 2.9 vs. 74.6 +/- 3.7 mm Hg; p less than or equal to 0.05), increased heart rate (236 +/- 11 vs. 216 +/- 8 beats/min; p less than or equal to 0.05) and renal vasoconstriction (vascular resistance 49.65 +/- 8.55 vs. 24.61 +/- 5.85 U; p < 0.05; blood flow velocity, 1.58 +/- 0.21 vs. 3.63 +/- 0.31 kHz; p < 0.05). ET-1 concentrations were significantly increased not only in plasma (7.67 +/- 0.47 vs. 4.56 +/- 0.69 pg/ml; p < 0.05) but also in renal tissue (4.8 +/- 0.5 vs. 3.5 +/- 0.64 pg/mg; p < 0.05). Northern analysis revealed an unchanged expression of ETA receptor messenger RNA (0.79 +/- 0.05 vs. 0.77 +/- 0.04 arbitrary units; NS) in renal tissue, whereas expression of prepro-ET-1 was below the range of detection. In CHF, selective ETA-receptor antagonism with BQ-123 (1 mg/ kg bolus, i.v.) significantly increased renal blood flow velocity (3.07 +/- 0.38 vs. 1.33 +/- 0.19 kHz; p < 0.05) and reduced renal vascular resistance (29.63 +/- 6.22 vs. 58.17 +/- 8.75 U; p < 0.05) without significant effects on mean arterial pressure or heart rate. These studies demonstrate activation of the renal ET system, unaltered gene expression, and functional integrity of the renal ETA receptor in CHF. They indicate a principal functional role for the ETA receptor in renal vasoconstriction and suggest blockade of the renal ETA receptor as an important strategy to attenuate renal hypoperfusion in CHF.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VASOCONSTRICTOR PEPTIDE; A RECEPTOR; EXPRESSION; POTENT; INHIBITION; MEDICINE; BLOCKADE; heart failure; renal hemodynamics; rabbit-endothelin-1; ETA receptor; BQ-123 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Dec 2022 10:40 |
| Last Modified: | 20 Dec 2022 10:40 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48955 |
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