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

We investigated the contribution of angiotensin II and endothelin to the sl ow positive inotropic response observed following stretch of isolated ferre t papillary muscle from 88% to 98% of the length at which maximum force is generated. Angiotensin antagonists losartan and saralasin did not affect th e magnitude of the slow response in ferret papillary muscle. The ETA-select ive antagonist BQ123 slightly reduced the magnitude of the slow response (P >0.05). In the presence of PD145065 (an ETA and ETB antagonist), the magnit ude of the slow response was reduced significantly by 50%. Removal of the e ndothelium with 1% Triton X-100 reversed the slow response to stretch. We c onclude that, in the ferret, endothelin 1 acting through ETA and ETB recept ors, 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 pivo tal role in this phenomenon in cardiac papillary muscle.