Contribution of angiotensin II, endothelin 1 and the endothelium to the slow inotropic response to stretch in ferret papillary muscle

Abstract.

We investigated the contribution of angiotensin II and endothelin 1 to the slow positive inotropic response observed following stretch of isolated ferret papillary muscle from 88% to 98% of the length at which maximum force is generated. Angiotensin antagonists losartan and saralasin did not affect the magnitude of the slow response in ferret papillary muscle. The ET_A-selective antagonist BQ123 slightly reduced the magnitude of the slow response (P>0.05). In the presence of PD145065 (an ET_A and ET_B antagonist), the magnitude of the slow response was reduced significantly by 50%. Removal of the endothelium with 1% Triton X-100 reversed the slow response to stretch. We conclude that, in the ferret, endothelin 1 acting through ET_A and ET_B receptors, contributes to the slow response although it is not the sole mediator. Angiotensin II is not a prerequisite for the slow response to stretch. We have shown for the first time that the endocardial endothelium plays a pivotal role in this phenomenon in cardiac papillary muscle.