Comparison of 2 endothelin-receptor antagonists on in vitro responses of equine palmar digital arterial and venous rings to endothelin-1.
The goals of this study were to determine the concentration-response (C-R) relationship of endothelin-1 (ET-1), compare 2 ET-receptor antagonists and determine the antagonist concentrations that block the vasomotor effects of ET-1, and compare the effectiveness of ET-1 and previously studied vasoconstrictors in equine palmar digital arterial and venous rings in vitro. Vessel rings from 8 nonlaminitic horses were placed in Tyrode's solution, 1 side fixed to the floor of an organ bath and the other side fixed to a force-displacement transducer. Two separate studies were conducted: (I) incubation with a single ET-receptor antagonist (PD142893 or PD145065 at a concentration of 10(-7), 10(-6), or 10(-5) M), followed by determination of an ET-1 C-R curve (using concentrations of 10(-10) to 10(-6) M) for medial vessel rings; and (II) comparison of ET-1 with norepinephrine and histamine (10(-10) to 10(-6) M) and comparison of contractile responses of medial and lateral vessel rings. In study I, ET-1 administration caused pronounced and sustained concentration-dependent contraction of vessel rings; these contractile responses were decreased by 10(-5) M PD142893 and were completely blocked by 10(-5) M PD145065. Venous rings had greater apparent maximum contraction in response to ET-1 than arterial rings. In study II, the relative sensitivity of norepinephrine was found to be equivalent to that of ET-1, whereas that of histamine was lower. No significant differences were observed between responses of medial versus lateral vessel rings. Thus, ET-1 is a potent vasoconstrictor of equine palmar digital arteries and veins, and the ET-receptor antagonist PD145065 is more effective than PD142893 in inhibiting these contractile effects in vitro.
Stokes
Ashley M
AM
Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge 70803-8410, USA. astokes@lsu.edu
Venugopal
Changaram S
CS
Hosgood
Giselle
G
Eades
Susan C
SC
Moore
Rustin M
RM
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006736:Horses / Q000502:physiology*; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides; D014034:Toes / Q000098:blood supply*; D014680:Veins / Q000187:drug effects / Q000502:physiology
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; C076213:PD 142893; C082887:PD 145065