Supersensitivity of atherosclerotic rabbit aorta to ergometrine is mediated by 5-HT2 receptors.
The concentration response curve of ergometrine in aortae from rabbits fed a high cholesterol diet for 12 weeks is biphasic. The first phase of the biphasic curve is antagonized by ketanserin, spiperone and cyproheptadine, but not by prazosin. pKB values are compatible with a 5-HT2 receptor mediated effect. The second phase is shifted to the right by prazosin, ketanserin and spiperone but not by cyproheptadine. In this case the pKB values are compatible with an alpha 1-adrenoceptor mediated effect. The concentration response curves for ergometrine and phenylephrine in aortae from control rabbits are monophasic and pKB values again indicate an alpha 1-adrenoceptor mediated response. Thus, ergometrine contracts the aortae of normal and cholesterol-fed rabbits via activation of alpha 1-adrenoceptors. The supersensitivity observed in atherosclerotic strips seems to reflect the appearance of a high affinity component mediated by 5-HT2 receptors.
Kalkman
H O
HO
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
Neumann
V
V
Brauner
V
V
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001161:Arteriosclerosis / Q000503:physiopathology*; D001835:Body Weight / Q000187:drug effects; D003533:Cyproheptadine / Q000494:pharmacology; D004874:Ergonovine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D011985:Receptors, Serotonin / Q000502:physiology*; D013134:Spiperone / Q000494:pharmacology
D011985:Receptors, Serotonin; D010656:Phenylephrine; D003533:Cyproheptadine; D013134:Spiperone; D007650:Ketanserin; D004874:Ergonovine