Amino Acids (1993) 4:127-132 Amino Acids © Springer-Verlag 1993 Printed in Austria Modulation by glycine on vascular effect of NMDA: in vivo experimental researches L. Berrino, S. Vitagliano, S. Maione, and F. Rossi Institute of Pharmacology and Toxicology, 1st Faculty of Medicine and Surgery, University of Naples Federico II, Naples, Italy Accepted July 8, 1992 Summary. The present study has been carried out to determine if glycine, an allosteric modulator of NMDA receptor, is involved in the vascular effect induced by the activation of the CNS NMDA receptors. Icy NMDA (from 0.01 to 1/.tg/rat in the 3rd ventricle) determined a significant increase in arterial blood pressure in conscious freely moving rats. Moreover, the hypertension was asso- ciated with behavioural modifications (jumping, rearing, teething and running). Glycine pretreatment (1 and 10/~g/rat icy), significantly increased the NMDA hypertension. Alone glycine did not cause any arterial blood pressure modifica- tion while it induced a slight sedation. HA-966 (an antagonist of the glycine site on NMDA receptor) administration (1-10 #g/rat icy 5 min before glycine) significantly antagonized the glycine effects on NMDA hypertension. Alone HA-966 neither modified arterial blood pressure nor antagonized NMDA hypertension. In conclusion, our investigations confirm NMDA recep- tor involvement in cardiovascular function and they demonstrate that in vivo glycine positively modulates NMDA receptor. Keywords: Amino acids - N-Methyl-D-aspartate (NMDA) - Glycine - HA-966 - Rat - Strychnine Introduction Our previous investigations have shown the excitatory amino acid (EAA) effects on the cardiovascular system and both physiological and pathological action have been seen. NMDA and KA receptors play a primary role in the cardio- vascular effects exerted by EAA (Lampa et al., 1988b; Maione et al., 1992); in conscious rats intracerebroventricular administration of EAA produced hyper- tension and tachycardia associated with behavioural modifications (Berrino et al., 1990); in anaesthetized rats glutamate, NMDA and kainate when adminis- tered intracerebroventricularly produce hypertension and bradycardia (Lampa