Cardiovascular Responses to Activation of Metabotropic Glutamate Receptors in the NTS of the Rat

Although several agonists and antagonists for different subtypes of metabotropic glutamate receptors (mGLURs) have become available in recent years, detailed information regarding their selectivity is not complete in the in vivo animal models. The purpose of the present investigation was to study the cardiovascular effects of microinjections of some of these mGLUR agonists and antagonists into the nucleus tractus solitarius (nTS). Microinjections (100 nl) of EC(50) concentrations of 3,5-DHPG (0.005 mM; mGLUR(1) agonist), APDC (17.3 mM; mGLUR(2/3) agonist), PPG (11.7 mM; mGLUR(8) agonist) and L-AP(4) (1 mM; mGLUR(4) agonist) into the nucleus tractus solitarius of urethane-anesthetized male Wistar rats elicited depressor and bradycardic responses which may be mediated by pre- and/or postsynaptic mechanisms. The blocking effect of mGLUR antagonists used here was not specific for any one type of glutamate receptors (GLURs). For example, AIDA (50 mM; mGLUR(1) antagonist) blocked the effects of EC(50) concentrations of 3,5-DHPG, and PPG. LY341495 (135 mM; mGLUR(2/3) antagonist) blocked all of the mGLURs and ionotropic GLURs. EGLU, APICA and MCCG (250 mM each; mGLUR(2/3) antagonists) blocked the effects of APDC, NMDA and AMPA. CPPG (80 mM) and MSOP (125 mM), mGLUR(4) antagonists, blocked the effects of 3,5-DHPG, PPG and L-AP(4.) D-AP7 (NMDA receptor antagonist) and NBQX (a non-NMDA receptor antagonist) did not alter the responses of any of the mGLUR agonists. The data presented may be useful in assessing the role of metabotropic and ionotropic GLURs in mediating different cardiovascular reflexes.