The mechanical counterpart of the endothelin-3 released by myocardial stretch: The Anrep effect

ENNIS IL; GARCIARENA CD; PÉREZ NG; DULCE RA; CAMILIÓN DE HURTADO MC; CINGOLANI HE

Cancún, México

Congreso; 26th Annual Meeting of the North American Section of the International Society for Heart Research; 2004

  Experiments were design to get further insight into the autocrine/paracrine chain of events that follows myocardial stretch and underlies the slow force response (SFR). In cat papillary muscles, an equivalent increase in force to that induced by stretch during the SFR was promoted by exogenous ET-1, ET-2 or ET-3 (5 nmol/L each). The ET ETA receptor antagonist BQ-123 abolished the SFR and the contractile response to ET-2 and ET-3, but not to ET-1. The pharmacological experiments therefore, seemed to indicate that either ET-2 or ET-3 but not ET-1 were the activators of the NHE leading to an increase in Na+i. Parallel experiments showed that ET-3 increases Na+i to a similar extent as ET-1 does when used at the same dosage (5 nmol/L). However, whereas the effect of both ET isoforms was blocked by the specific NHE blocker HOE 642, only ET-3 effect was BQ-123 sensitive. The abundance of ET-1, ET-2 and ET-3 mRNA was assessed by real time RT-PCR in papillary muscles after 15 min of stretch. At this time point, only ET-3 mRNA was found elevated ( 161±17 %). No significant change was detected in ET-1 (91±10 %)and ET-2 (79±14 %) expression. The specific blockade of Ang II AT1 while canceling the SFR prevented the increase in ET-3 mRNA (65±22 %) without affecting ET-1 (72±13 %) and ET-2 (119±31 %) mRNA levels. We propose that myocardial stretch triggers an autocrine/paracrine loop beginning with the release of preformed Ang II that stimulates the formation/release of ET-3. ET-3 is responsible for the increase in Na+i by activating the NHE-1 that results in the increase in contractility through the NCX operating in its reverse mode