Effects Of Dexmedetomidine In Different Concentrations On Vasoconstriction And Vasodilation Of Porcine Coronary Artery Rings In Vitro And Potential Mechanisms

ObjectiveThe dexmedetomidine is a new type of high selectivity α2adrenoceptorwith sedation, analgesia, inhibiting sympathetic activity, reduce stress response.Recent studies have revealed that the dexmedetomidine may increase coronaryperfusion, reduce myocardial oxygen consumption and infarct size withcardioprotective effect. But rapid infusion and large dosage ofdexmedetomidine are likely to cause some adverse cardiovascular reactionssuch as remarkable hypotension and bradycardia. This suggests that the effectof dexmedetomidine on cardiovascular system may be more complex than weknow and more researches are needed to explore the exact mechanism. Themain purpose of this study is to investigate the effects of dexmedetomidine onvasoconstriction and vasodilation of porcine coronary artery, and to explorepossible mechanisms.MethodsThe left anterior descending coronary was dissected and mounted carefullyto make artery ring(3～5mm)．The tension of the ring was recorded withPowerLab system．After preconstricted by KCl (60mmol/L), vasoconstrictive and dilating responses of the rings to dexmedetomidine in differentconcentrations (10-9,10-8,10-7,10-6,10-5mol/L）were recorded. The effects ofinhibitors of α2receptor blockers（Yohimbine hydrochloride）(10-5mol/L),potassium channels blockers (Tetraethtylamine, TEA)(10-5mol/L) andCyclooxygenase (Indomethacin, lndo)(10-5mol/L), eNOS (L-NAME)(10-5mol/L) on vasoconstrictive and dilating responses of dexmedetomidinewere observed.Results1.The vasoconstrictive and dilating responses of dexmedetomidine in differentconcentrations are concentration-dependent in KCl pre-constricted porcinecoronary artery. Dexmedetomidine in lower concentrations （10-9,10-8,10-7mol/L）dilated coronary arterial rings and dexmedetomidine in higherconcentrations (10-6,10-5mol/L) constricted coronary arterial rings. The dilationrates of the dexmedetomidine in lower concentrations (10-9,10-8,10-7mol/L) inrings with intact endothelium are respectively-9.10+2.00%,-12.16+2.64%,-16.17+5.96%. Compared with10-9mol/L, dilation rate of10-7mol/Ldexmedetomidine was significantly higher(P<0.05).The constriction rates ofdexmedetomidine in higher concentrations (10-6,10-5mol/L) were respectively14.08+2.87%,14.31+3.57%with no significant difference (P>0.05). Thedilation rates of the dexmedetomidine of lower concentrations(10-9,10-8,10-7mol/L) in rings without endothelium were6.87+1.06%,10.53+1.66%,14.35+3.14%respectively, and with significant difference (P<0.05) between10-9mol/L,10-7mol/L dexmedetomidine. The constrictionrates of dexmedetomidine in different concentrations (10-6,10-5mol/L) arerespectively13.93+2.25%,21.07+4.38%, with significant difference(P<0.05).Compared with rings with endothelium, the dilation rates orconstriction rates of dexmedetomidine（10-9，10-8,10-7,10-6mol/L）in ringswithout endothelium were not significantly different (P>0.05). But in10-5mol/Lof dexmedetomidine, the constriction rate was significantly different (P<0.05).2. After preconstricted with KCl (60mmol/L), both the inhibitor of eNOS(L-NAME)(10-5mol/L) and the potassium channel blocker (Tetraethtylamine，TEA)(10-5mol/L) attenuated the vasodilation responses of dexmedetomidinein coronary artery rings with intact endothelium. The α2-receptor blocker（Yohimbine）attenuated the vasoconstriction response.3. For the coronary artery rings without the endothelium, The potassiumchannel blocker (Tetraethtylamine， TEA)(10-5mol/L) attenuated thevasodilation response of dexmedetomidine in coronary artery rings withoutendothelium. The α2-receptor blocker（Yohimbine）and the cyclooxygenase(Indomethacin, lndo)(10-5mol/L) attenuated the vasoconstriction response.Conclusions1. The response of isolated porcine coronary arterial rings to lowerconcentrations of dexmedetomidine is vasodilative. However, the response ofisolated porcine coronary arterial rings to higher concentrations ofdexmedetomidine is vasoconstrictive. 2. Either vasodilative or vasoconstrictive responses of the porcine coronaryartery to dexmedetomidine in different concentrations demonstrateconcentration-dependent.3. The vasodilative effect of porcine coronary to dexmedetomidine in lowerconcentrations may be related to vascular endothelial cells, NO synthesis andcalcium activated potassium channels.4. The constrictive effect of porcine coronary to dexmedetomidine in higherconcentrations may be mediated by activation of alpha2receptors of vascularsmooth muscle and pathway of lipoxygenase.