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Objective:To observe and compare the effects of DZP on the contraction induced by 5-hydroxytryptamine (5-HT) in isolated thoracic aorta rings of adult and old rats; to explore the effects of drugs on the foregoing phenomena and their possible mechanisms.Methods:The method of isolated vascular tension record system was followed. The adult and old rats were sacrificed by cervical vertebra luxation and the thoracic aorta was quickly isolated from each animal and placed in cold physiological salt solution (PSS), then the surrounding connective tissues and fat were carefully removed. The vessel was cut into rings about 3-4mm in length. Two stainless-steel wires were passed through the lumen of each ring. One was fixed to the bottom of the bath chamber; the other was connected to an isometric force transducer (BL-420F system) to measure the tension of the ring. Rings were placed in a 10 ml chamber containing PSS (PH=7.4), bubbled with 100% O2, at 37℃. The rings were stretched until they exerted an optimal basal tension of 2g, and then were allowed to equilibrate for 1 hour with the bath fluid being changed every 15 minutes. Effects of DZP on the contractions induced by 5-HT in the thoracic aortic rings with intact endothelium or denuded endothelium were observed. The effects of various drugs include NG-nitro-L-arginine methyl ester (L-NAME,10-4 mol/L), indomethacin (Indo,10-5 mol/L) and PK11195 (10-6 mol/L), tetraethylammonium (TEA,10-2 mol/L),4-aminopyridine (4-AP, 10-3 mol/L), glibenclamide (Gli,10-5 mol/L), barium chloride (BaCl2,10-3 mol/L) were also studied.Results:(1) 5-HT (10-7-3×10-5 mol/L) could produce the concentration-dependent contractions in isolated thoracic aorta rings of adult and old rats. The EC50 of 5-HT was (3.41±0.18)×10-6 mol/L or (1.96±0.12)×10-6 mol/L in intact or denuded endothelium isolated thoracic aorta rings of adult rats respectively. The EC50 of 5-HT was(2.92±0.15)×10-6 mol/L or (3.15±0.15)×10-6 mol/L in intact or denuded endothelium isolated thoracic aorta rings of old rats respectively. (2) On the adult and old rats isolated thoracic aorta rings with intact or denuded endothelium, DZP (3×10-6 mol/L,10-4 mol/L) attenuated the 5-HT-induced vasoconstriction; DZP (3×10-6 mol/L,10-4 mol/L) decreased the 5-HT-induced maximal contraction compared with the rings not treated with Diazepam (P<0.01). (3) Pretreated with DZP 3×10-6 mol/L or DZP 10-4 mol/L in the adult and old rats isolated thoracic aorta rings, 5-HT-induced maximal contraction in the thoracic aorta rings with denuded endothelium is higher, compared with the thoracic aorta rings with intact endothelium (P<0.01). (4) Pretreated with DZP 3×10-6 mol/L or DZP 10-4 mol/L in the thoracic aorta rings with intact endothelium,5-HT-induced maximal contraction in the old rats isolated thoracic aorta rings is higher, compared with the thoracic aorta rings in adult rats (P<0.01). Pretreated with DZP 3×10-6 mol/L or DZP10-4 mol/L in the thoracic aorta rings with denuded endothelium, 5-HT-induced maximal contraction in the old rats isolated thoracic aorta rings is lower, compared with the thoracic aorta rings in adult rats (P<0.01). (5) DZP (3×10-6 mol/L) attenuated the 5-HT induced vasoconstriction, and the effects was abolished by L-NAME, TEA,4-AP, BaCl2 (P<0.01), however, Indo, PK11195, Gli did not have such effects. DZP (10-4 mol/L) attenuated the 5-HT induced vasoconstriction, and L-NAME,4-AP, BaCl2 abolished this effects (P<0.01), however, Indo, PK11195, TEA and Gli did not have such effects.Conclusions:5-HT produced the concentration-dependent contraction; DZP (3×10-6 mol/L, 10-4 mol/L) attenuated the 5-HT induced contraction in isolated thoracic aorta rings of adult and old rats. On the isolated thoracic aorta rings with intact endothelium,5-HT induced vasoconstriction in old rats was significantly enhanced compared with adult rats; however DZP-induced attenuation in old rats was significantly reduced compared with adult rats. The effect was contrary between the thoracic aorta rings with intact endothelium and denuded endothelium in rats. DZP-induced attenuation via endothelium-dependent mechanisms, probably by increasing NO release from the endothelium, but the effect was independent of the peripheral benzodiazepine receptor. DZP (3×10-6mol/L)-induced attenuation may have a relationship with Kir, KCa and KV. DZP (10-4 mol/L)-induced attenuation may be related to Kir and KV.
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