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 I 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 ETA-selective antagonist BQ123 slightly reduced the magnitude of the slow response (P > 0.05). In the presence of PD145065 (an ETA and ETB 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 I acting through ETA and ETB 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.
Calaghan
S C
SC
School of Biomedical Sciences, University of Leeds,  UK. s.c.calaghan@leeds.ac.uk
White
E
E
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D004727:Endothelium / Q000187:drug effects / Q000502:physiology; D005260:Female; D005289:Ferrets / Q000502:physiology*; D007700:Kinetics; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009470:Muscle Spindles / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects; D017830:Octoxynol / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010210:Papillary Muscles / Q000502:physiology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D012504:Saralasin / Q000494:pharmacology
D019332:Endothelin-1; D009842:Oligopeptides; D010456:Peptides, Cyclic; D000804:Angiotensin II; C082887:PD 145065; D017830:Octoxynol; D012504:Saralasin; D019808:Losartan; C072247:cyclo(Trp-Asp-Pro-Val-Leu)