Urocortin 1 administration from onset of rapid left ventricular pacing represses progression to overt heart failure

Area of Science:

• Cardiovascular Physiology
• Endocrinology
• Renal Physiology

Background:

• Urocortin 1 (Ucn1) involvement in heart failure (HF) pathophysiology is suggested, but its therapeutic impact on disease progression remains unclear.
• Early intervention in HF is crucial to mitigate adverse hemodynamic and neurohumoral changes.
• Understanding Ucn1's effects during the onset of cardiac overload is vital for developing novel HF treatments.

Purpose of the Study:

• To investigate the effects of Ucn1 administration on the progression of heart failure (HF) in a sheep model.
• To determine if Ucn1 can prevent or delay the development of overt HF following cardiac overload.
• To assess Ucn1's impact on hemodynamic parameters, renal function, and neurohumoral activation during HF induction.

Main Methods:

• Sheep underwent two 4-day periods of HF induction via rapid ventricular pacing combined with Ucn1 infusion or vehicle control.
• Hemodynamic parameters including cardiac output, left atrial pressure, and peripheral resistance were measured.
• Plasma levels of renin activity, aldosterone, endothelin-1, vasopressin, catecholamines, and natriuretic peptides were quantified. Urine sodium excretion and creatinine clearance were also assessed.

Main Results:

• Ucn1 significantly attenuated the decline in cardiac output and prevented increases in left atrial pressure and peripheral resistance compared to control.
• Ucn1 administration wholly prevented increases in plasma renin activity, aldosterone, endothelin-1, and vasopressin.
• Ucn1 maintained urine sodium excretion and creatinine clearance, while blunting increases in catecholamines and natriuretic peptides.

Conclusions:

• Urocortin 1 treatment initiated at the onset of cardiac overload effectively repressed hemodynamic and renal deterioration.
• Ucn1 mitigated adverse neurohumoral activation, thereby delaying the development of overt heart failure.
• These findings strongly support Ucn1 as a potential therapeutic option for early-stage heart failure.