Endothelin 1 versus endothelin 3 in the development of the slow force response to myocardial stretch.
BACKGROUND
Myocardial stretch promotes an increase in developed force (DF) in two phases: a rapid initial phase, and a slowly developing second phase called the slow force response (SFR) to myocardial stretch. The SFR results from an autocrine/paracrine mechanism of angiotensin II and endothelin (ET) release that is triggered by the stretch.


OBJECTIVE
To explore whether exogenous ET-1 and/or ET-3 could mimic the SFR.


METHODS
Experiments were performed in isometrically contracting (0.2 Hz) rat papillary muscles at 30 degrees C. DF was measured either after stretch or after the addition of ET-1 or ET-3 (in doses that increase contractility to a similar magnitude as does the SFR), with or without the selective ETA receptor antagonist BQ123 (300 nmol/L).


CONCLUSIONS
After 15 min, the SFR was 17.6+/-1.4% greater than the initial rapid phase (n=4; P<0.05) and was abolished by BQ123. ET-1 (5.0 nmol/L) increased DF by 25.9+/-1.7% (n=4; P<0.05) after 30 min, an effect that was not altered by BQ123 (22.6+/-3.9%; n=5). ET-3 (5.0 nmol/L) increased DF by 23.8+/-3.2% (n=5; P<0.05), an effect that was suppressed by BQ123 (-5.4+/-1.9%; n=5; P<0.05). Given that BQ123 eliminated the SFR and the inotropic response to ET-3 but not to ET-1, the results suggest that the SFR that follows myocardial stretch is due to the endogenous release of ET-3 acting in an autocrine/paracrine fashion.
Ros
María N
MN
Residencia de Cardiología, Hospital Italiano de La Plata, La Plata, Argentina.
Dulce
Raúl A
RA
Pérez
Néstor G
NG
Camilión de Hurtado
María C
MC
Cingolani
Horacio E
HE
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D019334:Endothelin-3 / Q000494:pharmacology*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects*; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D019334:Endothelin-3; D010456:Peptides, Cyclic; D014662:Vasoconstrictor Agents; C072247:cyclo(Trp-Asp-Pro-Val-Leu)