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Long-term adrenomedullin administration in experimental heart failure
Miriam T Rademaker1, Chris J Charles, Eric A Espiner
1Christchurch Cardioendocrine Research Group, Department of Medicine, The Christchurch School of Medicine, Christchurch, New Zealand. miriam.rademaker@chmeds.ac.nz
Hypertension (Dallas, Tex. : 1979)
|November 2, 2002
Summary
Long-term adrenomedullin administration improved heart failure in sheep by increasing cardiac output and sodium excretion while reducing resistance and pressure. This peptide shows therapeutic potential for heart failure.
Area of Science:
- Cardiovascular Research
- Nephrology
- Endocrinology
Background:
- Short-term adrenomedullin (AM) shows benefits in heart failure.
- Prolonged AM effects in heart failure are unstudied.
Purpose of the Study:
- To assess the effects of prolonged (4-day) adrenomedullin administration in experimental heart failure.
Main Methods:
- 16 sheep with pacing-induced heart failure received either adrenomedullin (10 ng/kg/min) or vehicle control for 4 days.
- Hemodynamic, renal, and hormonal parameters were monitored.
Main Results:
- Adrenomedullin significantly increased cardiac output (27%) and enhanced sodium excretion (3-fold) and creatinine clearance (1.4-fold).
- It reduced peripheral resistance (30%), mean arterial pressure (13%), and left atrial pressure (24%).
- Aldosterone levels were reduced, while plasma renin activity increased; endothelin rose transiently.
Conclusions:
- Long-term adrenomedullin administration exerts sustained beneficial cardiovascular and renal effects in experimental heart failure.
- It reduces cardiac preload and afterload, augments cardiac output, and improves renal function.
- Adrenomedullin demonstrates therapeutic potential for heart failure management.