Intrathecal kynurenate reduces arterial pressure, heart rate and baroreceptor-heart rate reflex in conscious rats.
In the present study, an excitatory amino acid (EAA) pathway in the spinal cord which maintains sympathetic vasomotor tone in conscious rats has been investigated. To this end, the cardiovascular effects of an intrathecally administered EAA antagonist, kynurenate (KYN), were studied in conscious rats. KYN (0.5 mumol in 10 microliters) caused a dramatic reduction in mean arterial pressure (MAP) and heart rate (HR) that persisted for 2-3 h, and also resulted in extensor paralysis of the hindlimbs. The time courses of fall in MAP and HR and hindlimb paralysis were similar. Baroreceptor-HR reflex activity was also markedly impaired after KYN, suggesting functional diminution of sympathetic outflow at the level of the spinal cord after blockade of EAA receptors by KYN. Xanthurenate, a metabolite of KYN without EAA antagonistic properties, produced negligible effects at the same dose of KYN. While these findings do not identify the putative EAA pathway, they do provide the first demonstration that this system is tonically active in conscious rats.
University of Melbourne, Clinical Pharmacology and Therapeutics Unit, Austin Hospital, Heidelberg, Vic., Australia.
A J
AJ
Verberne
R E
RE
Widdop
C
C
Maccarrone
B
B
Jarrott
P M
PM
Beart
W J
WJ
Louis
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D007736:Kynurenic Acid / Q000494:pharmacology*; D008297:Male; D011311:Pressoreceptors / Q000502:physiology; D051381:Rats; D012018:Reflex / Q000187:drug effects*
D007736:Kynurenic Acid