Localization of immunoreactive endothelin and characterization of its receptors in aortic cusps.
OBJECTIVE
Aortic valve cusp tissue has been shown to have contractile properties in response to a range of common vasoactive agents. Of these, endothelin (ET) is both the most potent and efficacious.


METHODS
In an attempt to define the mechanism of action and localization of ET, the response of porcine aortic valve cusps to ET and the selective ET(B) receptor agonist sarafotoxin 6c (S6c) was examined, in the presence and absence of ET(A) and ET(B) receptor antagonists. An attempt was made, using immunocytochemical techniques, to localize ET in cusp tissue.


RESULTS
Addition of 90 mM KCl produced a mean contractile response of 1.02+/-0.09 mN (n = 27). ET (10- to 10(-7)M) produced a concentration-dependent contraction of aortic valve cusps, with a maximum response of 116.7+/-12.7% (n = 6) of that obtained with 90 mM KCl. In a similar manner, 10(-5)M of the selective ET(A) receptor antagonist BQ123 (n = 4) and 10(-5)M of the selective ET(B) receptor antagonist BQ788 (n = 4) each partially inhibited the effect of ET. The ET(B)-selective agonist S6c (10(-9) to 10(-7)M) also induced a concentration-dependent contraction of valve cusps (n = 4), with a maximum response of 99.1+/-11.1%. This response was completely inhibited by 10(-5)M BQ788 (n = 4). Immunoreactive ET was localized to the endothelial cells that lined both the ventricular and aortic side of the cusps.


CONCLUSIONS
These results show that aortic valve cusps contract to ET via an action at both ET(A) and ET(B) receptors. The presence of immunoreactive ET in the endothelial cells of the cusps also suggests that it might play a role in valve function. Further studies are required to elucidate the role of these receptors in the physiology and pathophysiology of the aortic valve.
Misfeld
Martin
M
Department of Cardiothoracic Surgery, Heart Science Centre, Harefield Hospital, NHLI, Imperial College of Science Technology and Medicine, UK.
Morrison
Karen
K
Sievers
HansH
H
Yacoub
Magdi H
MH
Chester
Adrian H
AH
D000704:Analysis of Variance; D000818:Animals; D001021:Aortic Valve / Q000187:drug effects / Q000473:pathology*; D046508:Culture Techniques; D016232:Endothelins / Q000032:analysis / Q000276:immunology / Q000494:pharmacology*; D005629:Frozen Sections; D007150:Immunohistochemistry; D023421:Models, Animal; D009200:Myocardial Contraction / Q000187:drug effects*; D010456:Peptides, Cyclic / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000187:drug effects*; D012016:Reference Values; D012680:Sensitivity and Specificity; D013552:Swine; D014757:Viper Venoms / Q000494:pharmacology*
D016232:Endothelins; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; D014757:Viper Venoms; C057354:sarafotoxins s6; C072247:cyclo(Trp-Asp-Pro-Val-Leu)