The Cardiovascular Inhibition Of Sulfur Dioxide In The Caudal Ventrolateral Medulla Of Anesthetized Rats Is In Relation With Glutamate Receptor Activation And SGG-cGMP Signal Transduction Pathway

Objective:To investigate the cardiovascular functions and mechanisms of sulfur dioxide microinjected into the caudal ventrolateral medulla (CVLM) of rats.Methods:Eighty-nine anesthetic male Spargue-Dawley rats weighting range220-300g were employed in present study. The dose-dependent responses of blood pressure and heart rate of sulfur dioxide of water-solution (2,20,200pmol) in the CVLM were determined by unilateral microinjection sulfur dioxide of water-solution or artificial cerebrospinal fluid (aCSF) into the CVLM in twenty-five rats (Given amount of reagent injection in this experiment were100nl, the following omitted). Bilateral microinjection of sulfur dioxide of water-solution (2,20,200pmol) into the CVLM in twenty-five rats to observe cardiovascular effects of sulfur dioxide of water-solution.In twenty-five rats, Glutamate inotropic of non-selective receptors antagonist KYN (15nmol), ATP-sensitive potassium channels (KATP) blocker glibenclamide (Gli,40μmol) or L-type calcium channels blocker nicardipine (Nic,200pmol) were respectively applied into CVLM of rats10min before sulfur dioxide of water-solution (20pmol) was microinjected. The other fourteen rats, aCSF, a non-specific nitric-oxide synthase inhibitor NG-nitro-L-arginine-methylester (L-NAME,15nmol) or soluble guanylyl cyclase (sGC) inhibitors1-H-1,2,4oxadiaolo[4,-a]quinoxalin-l-one (ODQ,250pmol) were prior applied before sulfur dioxide of water-solution (20pmol) was microinjected to explore the signal transduction pathway of sulfur dioxide.Results:①Unilateral application of sulfur dioxide of water-solution (2,20,200pmol) into the CVLM caused the transient and dose-dependent hypotension and bradycardia (P<0.05), and subsequently the values gradually recovered to the basal level in about one minute.②Bilateral application of sulfur dioxide of water-solution (2,20,200pmol) into the CVLM caused the transient and dose-dependent hypotension and bradycardia (P<0.01).③Injection of non-selective glutamate receptor antagonist kynurenic acid (Kyn5nmol) into the CVLM produced increase in BP (P<0.05) and HR (P<0.05), The hypotension (P<0.05) and bradycardia (P<0.01) induced by intra-CVLM sulfur dioxide of water-solution were decreased about50%and89%,respectively, compared with pretreatment with vehicle. Microinjections of glibenclamide (Gli40μmol) or nicardipine (Nic200pmol) into the CVLM have no effect on BP and HR was caused by sulfur dioxide of water-solution compared with pretreatment with vehicle.④Likewise, prior injection of soluble guanylyl cyclase (sGC) inhibitors1-H-1,2,4oxadiaolo[4,-a]quinoxalin-l-one (ODQ,0.25nmol) also attenuated the effects of sulfur dioxide of water-solution on BP (P<0.01) and HR (P<0.05). However, prior injection of non-specific nitric-oxide synthase inhibitor NG-nitro-L-arginine-methylester (L-NAME,10nmol) attenuated the effects of sulfur dioxide of water-solution on HR(P<00.01), has no effects on BP (P>0.05).Conclusion:①Unilateral microinjection of sulfur dioxide of water-solution into the CVLM produced dose-dependent hyperpiesia and tachycardia (P<0.05).②Bilateral application of sulfur dioxide of water-solution into the RVLM produced dose-dependent hyperpiesia and tachycardia (P<0.01).③SO2produces cardiovascular inhibition in the CVLM, mediated partly by glutamate receptor activation and sGC-cGMP signal transduction pathway.④CVLM regulated blood pressure by glutamate receptors and sGC-cGMP signal transduction pathways.