Involvement of 5‐HT_1B receptors in collar‐induced hypersensitivity to 5‐hydroxytryptamine of the rabbit carotid artery

Abstract

1 In humans intimal thickening is a prerequisite of atherosclerosis. Application of a silicone collar around the rabbit carotid artery induces an intimal thickening but in addition it increases the sensitivity to the vasoconstrictor action of serotonin (5-hydroxytryptamine, 5-HT). The 5-HT receptors involved in collar-induced hypersensitivity to 5-HT were investigated using several agonists and antagonists. 2 One week after placement of collars around both carotid arteries of anaesthetized rabbits, rings (2 mm width) from inside (=collar) and outside (=sham) the collars were mounted in organ baths (10 ml) for isometric force measurements at 6 g loading tension.3 Collared rings were more sensitive to the contractile e ect of 5-HT (7.6 fold) and 5-carboxamidotryptamine (31 fold, 5-CT, 5-HT 1 agonist) in cumulative concentration response curves. Sumatriptan (5-HT 1B/1D agonist) caused concentration-dependent constrictions in collared rings only. 5 In contrast, the apparent pK b value of methiothepin (5-HT 1B antagonist) was signi®cantly reduced by collar placement, and its antagonism shifted from non-surmountable in sham rings to surmountable in collared segments. 6 Taken together, this study demonstrates that the serotonergic receptor involved in the hypersensitivity to 5-HT of rabbit collared carotid artery is a 5-HT 1B receptor subtype.

Selective Clearance of Macrophages in Atherosclerotic Plaques by the Protein Synthesis Inhibitor Cycloheximide

“…A 2-mm segment was cut from each collar-wrapped carotid artery and mounted in organ chambers filled with 10 ml of physiological salt solution (118 mM NaCl, 4.7 mM KCl, 2.5 mM CaCl 2 , 1.2 mM KH 2 PO 4 , 1.2 mM MgSO 4 , 25 mM NaHCO 3 , 0.025 mM CaEDTA, and 11.1 mM glucose) at 37°C, continuously aerated with 95% O 2 /5% CO 2 for force measurements at 6 g loading tension as described previously (Geerts et al, 1999). Tension was measured isometrically with a Statham UC2 force transducer (Gould, Cleveland, OH) connected to a data acquisition system (Moise 3; EMKA Technologies, Paris, France).…”

Enhanced Contraction to 5-Hydroxytryptamine Is Not Due to “Unmasking” of 5-Hydroxytryptamine 1B Receptors in the Mesenteric Artery of the Deoxycorticosterone Acetate–Salt Rat

“…3,4 Recently, 5-HT 1B receptors have also been implicated as mediators of 5-HT-induced vasoconstriction. The 5-HT 1B receptor has been shown to mediate contraction in human pulmonary artery, 5 rat pulmonary artery, 6 human coronary artery, 7 human cerebral artery, 8 rabbit carotid artery, 9 rabbit ear artery, 10 rabbit renal artery, 11 and rat tail artery. 12 The 5-HT 1B receptor appears to be the predominant receptor mediating 5-HT-induced contraction in the human cerebral arteries.…”

Lacidipine has antiatherosclerotic effects independent of its actions on lipid metabolism and blood pressure

“…For the first time, we showed that lacidipine could reverse the increased sensitivity to 5-HT in early atherosclerosis. The increased expression of 5-HT-1B receptor is reported to be involved in hypersensitivity to 5HT-induced contraction in collared arteries (Geerts et al, 2000, Geerts et al, 1999) as in pathological conditions (Kaumann & Levy, 2006) and stimulation of the migration and proliferation of SMC (Fanburg BL, 1997, Sharma et al, 1999). 5HT-1B receptor induced hypersensitivity is reported due to sensitization of the contractile myofilaments to Ca ++ via voltage-dependent Ca ++ channels (Hill et al, 2000).…”