Effect of nitrotyrosine on ?-adrenergic receptor-mediated vascular reactivity in rats / 中华麻醉学杂志

ABSTRACT

Objective3-nitro-L-tyrosine(3-NT)has been shown to be the marker of ONOO-productionin the tissue during septic shock.We aimed to investigate the effects of 3-NT on adrenergic receptor-mediatedvascular reactivity and the possible mechanism.Methods The experiment consisted of two parts.In part Ⅰ twenty-four male SD rats weighing 200-300g were anesthetized with intraperitoneal pentobarbital 40 mg?kg~(-1).Spontaneousbreathing was maintained.The animals were randomly divided into 2 groupsA control group received normalsaline i.v.(n=12)and B 3-NT group received 3-NT 2.5 ?mol?kg~(-1) i.v.(n=12).30 min and 90 min after 3-NT/N.S.administration the animals received i.v.phenylephrine(PE)0.5,1.0,1.5,2.0,2.5 ?g?kg~(-1)(subgroup Ⅰ)or vasopressin 1.3,2.6,3.9,5.2 ?g?kg~(-1)(subgroup Ⅱ)at 15 min intervals.The percentageincrease in MAP was recorded.In part Ⅱ six male SD rats were anesthetized and killed.The thoracic aorta wasimmediately removed and aortic rings of 3 cm in length were prepared and suspended in Krebs-Hensleit solutionmaintained at 37℃ and aerated with 95% O_2 and 5% CO_2 and prestretched with a load of 2g.Before theexperiment the response of the aortic tings to cumulative addition of PE(1?10~(-9)-3?10~(-5)mol)was prelimarilymeasured.Alter five washes the aortic rings were randomly divided into 2 groupscontrol group(KH solution)and 3-NT group(KH solution containing 3-NT 250 ?mol?L~(-1)).After 60 min incubation,response to PE wasmeasured in both groups and concentration-response curve was obtained and Emax and CE_50 were calculated.Results PE increased MAP in a dose-dependent manner.PE 2.5 ?g?kg~(-1) increased MAP by 20% of thebaseline value.30 and 90 min after 3-NT 2.5 ?mol?kg~(-1) the hypertensive response of the animal to PE wassignificantly inhibited but 3-NT did not affect the increase in MAP induced by vasopressin.In the isolated SD rataortic ring experiment there was no significant difference in the concentration-response curve and Emax and EC50values of PE between the 3-NT and control group.Conclusion 3-NT selectively inhibits ?-adrenoceptor mediatedhemodynamic response through mechanisms other than competitively antagonizing ?-adrenoceptor.