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Renal effects of big endothelin-1 in experimental congestive heart failure
K Gurbanov1, J Winaver, A Haramati
1Department of Physiology and Biophysics, Faculty of Medicine, Technion, Haifa, Israel.
Insights
Congestive heart failure (CHF) in rats reduces sensitivity to big endothelin (ET). This peptide impacts blood pressure and kidney function differently in healthy versus CHF models, indicating altered ET receptor activity.
Area of Science:
- Physiology
- Nephrology
- Cardiology
Background:
- Endothelin (ET) plays a crucial role in regulating cardiovascular and renal functions.
- Congestive heart failure (CHF) is associated with significant alterations in hemodynamic and excretory processes.
- The specific impact of big ET on renal hemodynamics and function in experimental CHF models requires further elucidation.
Purpose of the Study:
- To investigate the effects of big endothelin (ET) on renal hemodynamics and excretory functions.
- To compare the responses to big ET in control rats versus rats with experimental congestive heart failure (CHF).
Main Methods:
- Experimental congestive heart failure (CHF) was induced in rats via an aortocaval fistula.
- Clearance studies were conducted in both control and chronic (7-day) CHF rats.
- Intravenous administration of big ET (1 and 3 nmol/kg) was performed to assess hemodynamic and excretory changes.
Main Results:
- In control rats, big ET increased mean arterial pressure (MAP), renal vascular resistance (RVR), and sodium excretion, while decreasing renal blood flow (RBF) and glomerular filtration rate (GFR).
- In CHF rats, the effects of big ET on MAP and RBF were blunted.
- Despite increased GFR in CHF rats, sodium excretion response to big ET was minimal, suggesting reduced renal sensitivity.
Conclusions:
- Rats with experimental CHF exhibit a blunted response to the vascular actions of big ET.
- The renal effects of big ET, including sodium excretion and GFR modulation, are significantly altered in CHF.
- These findings suggest that CHF is associated with reduced sensitivity to the overall actions of endothelin.
Abstract:
The present study was designed to evaluate the effects of big endothelin (ET) on renal hemodynamics and excretory functions in rats with experimental congestive heart failure (CHF) produced by aortocaval fistula. Clearance studies were performed in control and in chronic (7 day) CHF rats. Administration of bit ET (1 and 3 nmol/kg, i.v.) to control rats caused an increase (29%) in mean arterial pressure (MAP) associated with a decrease (38%) in renal blood flow (RBF) and a marked increase (130%) in renal vascular resistance (RVR). These changes were accompanied by a decrease in glomerular filtration rate (GFR) and a significant increase in sodium excretion. In contrast, the effects of big ET on MAP and renal hemodynamics were blunted in CHF rats, and sodium excretion increased only minimally in response to big ET despite a significant increase in GFR. The data suggest that rats with CHF have reduced sensitivity to the vascular and renal action of ET.