Abstract 13342: The Antagonistic Effect of Apelin on Endothelin-1 Mediated Vasoconstriction is Lost in Heart Failure
Purpose: The novel peptide apelin is ubiquitously expressed throughout the cardiovascular system and has vasodilator and inotropic properties. It is therefore hypothesized that apelin may be of pathophysiological and therapeutic significance in heart failure (HF). We investigated the interaction of apelin with endothelin-1, a key neurohormone in the development and progression of HF, in healthy rabbits and rabbits with HF.
Methods: Mesenteric arteries (MA) were obtained from healthy (n=12) and HF (n=12) male New Zealand White rabbits. HF was induced by coronary artery ligation under general anesthetic with sacrifice 8 weeks post-procedure. MA segments were isolated and mounted on a 4-channel myograph. Vessels without intact endothelium were discarded. Four MA segments were obtained from one animal for each experiment. Two were incubated with 1µM of apelin and two were untreated controls. Thirty minutes later, cumulative concentration-response curves were constructed for endothelin-1 (1x10-10M-3x10-7M) in all vessels.
Results: In healthy arteries endothelin-1 produced concentration-dependent constriction (max 78[SEM 3]%) which was attenuated by pretreatment with apelin (maximal contraction 68[SEM 3]%, p<0.05) (Fig 1). This antagonistic effect was abolished in arteries from HF animals-maximal constriction in untreated 77(SEM 3)% vs 73(SEM 3)% in apelin treated vessels (p=0.42) (Fig 2).
Conclusion: Apelin attenuates the vasoconstrictor action of endothelin-1 in healthy animals but not animals with HF. This provides new insight into the neurohormonal interactions of apelin and suggests that some potentially advantageous actions of apelin are lost in HF.
- © 2011 by American Heart Association, Inc.