Sinoaortic denervation abolishes blood pressure-induced GABA release in the locus coeruleus of conscious rats.
Male Sprague-Dawley rats underwent sinoaortic denervation (SAD) or sham operation. We examined changes in the release rates of GABA, glutamate and arginine in the locus coeruleus (LC) elicited by experimental blood pressure increases (i.v. noradrenaline infusion for 3 min, 4 microg kg(-1)min(-1)) or decreases (i.v. sodium nitroprusside infusion for 3 min, 150 microg kg(-1)min(-1)). The release of the neurotransmitters was monitored by the push-pull superfusion technique. Mean blood pressure did not differ between sham-operated and SAD rats but blood pressure lability was greatly enhanced in SAD rats and accompanied by increased basal release of glutamate in the LC. GABA release was not affected. A rise in blood pressure induced by noradrenaline enhanced GABA release in the LC of sham-operated rats. This effect was abolished by SAD. Glutamate release did not respond to hypertension either in SAD or in sham-operated rats. Nitroprusside led to a fall in blood pressure which was more pronounced and lasted longer in SAD than in sham-operated rats. In SAD rats, glutamate release was enhanced by nitroprusside. The depressor response had no effect on glutamate release in sham-operated rats. GABA release did not respond to this stimulus in either SAD or sham-operated rats. SAD and blood pressure changes did not influence the release rate of arginine. In conclusion, experimental hypertension increases GABAergic activity in the LC by stimulating peripheral baroreceptors. In SAD rats, augmented blood pressure lability seems to be at least partly due to elevated glutamate outflow within the LC.
Kouvelas
Dimitrios
D
Department of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, P.O. Box 1532, 54006 Thessaloniki, Greece. kouvelas@auth.gr
Singewald
Nicolas
N
Kaehler
Stefan T
ST
Philippu
Athineos
A
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D017763:Autonomic Denervation / Q000379:methods*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002243:Carbolines / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D007823:Laryngeal Nerves / Q000502:physiology; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017783:Superior Cervical Ganglion / Q000502:physiology; D013997:Time Factors; D014851:Wakefulness; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000959:Antihypertensive Agents; D002243:Carbolines; D009599:Nitroprusside; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C009804:tryptoline