NO-cGMP pathway at ventrolateral medullary cardiac inhibitory sites enhances the baroreceptor reflex bradycardia in the rat.
The neuronal isoform of the enzyme nitric oxide synthase (nNOS) has been identified in the caudal ventrolateral medulla of the rat close to the location of cardiac vagal motoneurones. Therefore in this study we tested identified ventral medulla cardioinhibitory sites for the involvement of nitric oxide (NO) in the baroreceptor-heart rate reflex pathway. In rats anaesthetised with a mixture of urethane (650 mg kg(-1)) and chloralose (50 mg kg(-1)) i.v., blood pressure and heart rate were monitored continuously and using stereotaxic coordinates the ventrolateral caudal brainstem within and around the nucleus ambiguus was systematically explored for sites producing a bradycardia of >50 bpm, without a change in blood pressure, using D,L homocysteic acid (DLH, 0.2 M) microinjections (50 nl) from a glass micropipette. Identified sites were marked with pontamine sky blue. Microinjection of the NO donor sodium nitroprusside (SNP, 1 mM, 50 nl) at a cardioinhibitory site also produced a significant bradycardia (68+/-14 bpm) while the NOS inhibitor N(G)-nitro-l-arginine (l-NNA) (3 mM, 50 nl) caused a small significant increase in heart rate (5+/-1 bpm). Baroreceptor reflex gain measured by the response in heart rate to a change in blood pressure induced by phenylephrine i.v. was significantly increased (610+/-171%, p<0.05) during the steady state of the response to SNP, whereas it was significantly reduced (73+/-5%, p<0.01) by l-NNA injection at a medullary cardioinhibitory site. An inhibitor of soluble guanylyl cyclase, (1)H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ, 1 mM, 50 nl) also significantly reduced the baroreceptor reflex gain (63+/-8%, p<0.05). The results suggest that a NOS-cGMP signalling system in the baroreceptor reflex pathway distal to the NTS and closer to cardiac vagal motoneurones in the caudal ventral medulla contributes to enhancement of cardiac vagal tone.
Fletcher
Janine
J
Department of Physiology, The Medical School, The University of Birmingham, Birmingham B15 2TT, UK. J.X.Fletcher@wlv.ac.uk
Moody
William E
WE
Chowdhary
Saqib
S
Coote
John H
JH
D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D001919:Bradycardia / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D006339:Heart Rate / Q000502:physiology; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D009433:Neural Inhibition / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology
D009569:Nitric Oxide; D006152:Cyclic GMP