Constriction of porcine arteriovenous anastomoses by indorenate is unrelated to 5-HT1A, 5-HT1B, 5-HT1C or 5-HT1D receptor subtypes.
The study concerns the effects of indorenate, a tryptamine derivative with antihypertensive properties as well as high affinity for the 5-HT1A binding site, on carotid haemodynamics in anaesthetized pigs. Intracarotid infusions of indorenate (0.3, 1.0, 3.0 and 10.0 micrograms.kg-1.min-1 for 10 min each) caused dose-related decreases in total common carotid artery blood flow due almost exclusively to a reduction in arteriovenous anastomotic flow. These effects of indorenate were not appreciably modified after treatment with the 5-HT2 receptor antagonist ketanserin (0.5 mg.kg-1 i.a.), but were markedly reduced after treatment with methiothepin (1.0 mg.kg-1 i.a.), which antagonizes not only 5-HT2 receptors, but also the putative 5-HT1A, 5-HT1B 5-HT1C and 5-HT1D subtypes of 5-HT1-like receptors. Nonetheless, metergoline (1 mg.kg-1 i.a.), a drug with higher affinity than methiothepin for the above 5-HT1 receptor subtypes, failed to significantly modify the responses to indorenate. It is therefore concluded that, like 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU 24969), indorenate reduces both total common carotid and cephalic arteriovenous anastomotic blood flow in the pig by stimulating 5-HT1-like receptors; these receptors, however, do not seem to correspond to either 5-HT1A, 5-HT1B, 5-HT1C or 5-HT1D binding sites.
Villalón
C M
CM
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands.
Bom
A H
AH
Heiligers
J P
JP
Den Boer
M O
MO
Saxena
P R
PR
D008735:5-Methoxytryptamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001166:Arteriovenous Shunt, Surgical; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008719:Methiothepin / Q000494:pharmacology; D008863:Microspheres; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*
D000959:Antihypertensive Agents; D011985:Receptors, Serotonin; D008735:5-Methoxytryptamine; D008719:Methiothepin; C033600:indorenate