Kynurenic acid as an additional endogenous anti-aggregatory factor

Kynurenic acid [KNA] is an endogenous metabolite of tryptophan that has been characterized both in the brain and various peripheral organs that included blood vessels, kidneys, hearts, intestine and the eye. Its release from the vascular tissues which also release prostacyclin and nitric oxide directed us to investigate its influence on platelets aggregation. Exposure of guinea-pig platelets to KNA in concentrations ranging from 0.1 to 2mM inhibited adenosine diphosphate [ADP] and arachidonic acid [AA] induced aggregations in a dose-dependent manner.The inhibitory dose 50 values against ADP and AA were found to be 1.1 +/- 0.06 and 0.9 +/- 0.08 mM respectively. [N=8]. The anti-aggregatory effect was significantly reversed in presence of exogenous Ca[2+]. Elevation of the level of the plasma by 0.5mM Ca[2+] reversed the anti-aggregatory effect KNA by 60 +/- 4.5 and 71.5 +/- 6.3% against ADP and AA, respectively [P<0.01, N=8]. It is suggested that KNA may be considered as an additional endogenous anti-aggregatory factor

Putative pathways involved in cardiovascular responses evoked from the caudal pressor area

1. The caudal pressor area (CPA) is a recently identified site within the ventrolateral medulla which is involved in cardiovascular regulation. CPA chemical stimulation by L-glutamate produces an increase in arterial blood pressure (ABP) while its inhibition by GABA or glycine evokes marked hypotension. In the present study, we sought to determine the potential neural pathways underlyng these responses. 2. In urethane-anesthetized, paralyzed, artificially ventilated rats, CPA inhibition by bilateral microinjection of the inhibitory amino acid glycine (Gly, 100 nmol 200 nl-1 site-1) produced an average decrease of -38 + or - 4.3 mmHg in ABP (n = 6). Ten min after bilateral microinjection of the broad-spectrum glutamate antagonist kynurenic acid (KYN, 2 nmol 200 nl-1 site-1) into the cauldal ventrolateral medulla (CVLM) depressor responses to CPA inhibition were virtually abolished (-3 + or - 1.7 mmHg, P<0.05). Similar microinjection of KYN into the rostral ventrolateral medulla (RVLM) or into the CPA itself did not modify depressor responses to CPA inhibiton by glycine. 3. CPA stimulation by bilateral microinjection of the excitatory amino acid L-glutamate (L-glu, 50 nmol 200 nl-1 site-1) produced an increase in ABP (+43 + or - 5.4 mmHg, N= 6). Bilateral microinjection of the GABA A antagonist bicuculline methiodide (BIC, 200 pmol 200 nl-1 site-1) into the CVLM markedly reduced pressor responses to CPA stimulation (+6 + or - 2.7 mmHg, P<0.05). Similar application of BIC into the RVLM or CPA did not modify pressor responses to CPA stimulation by glutamic acid

Anxiolytic effect of kynuremic acid microinjected into the dorsal periaqueductal gray matter of rats placed in the elevated plus-mase test

The effect of kynurenic acid (20 to 19=60 nmol) microinkected into the dorsal periaqueductal gray matter was measured in rats placed in a elevated plus-maze. Microinjection of 160 nmol of kynurenic acid increased the percentages of open arm entries and of time spent in the open arms. Both of these measures may be considered indexes of anciolysis. Although kynurenic acid also invreased the total number of entries, analysis of covariance shows that the increase in open arm entries is independent of the effect on closed arm entries. Thus, the anxiolytic effect of kynurenic acid detected in the elevated plus-maze strengthens the proposal that glutamatergic neurons of the dorsal periaqueductal gray matter paly an important role in anxiety