Activation of spinal metabotropic glutamate receptors elicits cardiovascular responses in pentobarbital anesthetized rats.
The aim of this study was to examine whether intrathecal (i.t.) injection of metabotropic glutamate (mGlu) receptor agonists at the thoracolumbar level of the spinal cord causes changes either in the blood pressure or in the heart rate of pentobarbital anesthetized rats. The broad spectrum mGlu receptor agonist (+/-)-1-aminocyclopentane- trans-1,3-dicarboxylic acid ( trans-ACPD) and the Group III mGluR agonist L-(+)-2-amino-4-phosphonobutyric acid ( L-AP4) induced pressor effects at doses of 300 nmol and 600 nmol (i.t.) but did not induce changes at a lower dose (150 nmol, i.t.). The specific Group I mGlu receptor agonist ( RS)-3,5-dihydroxyphenylglycine (3,5-DHPG), as well as the highly selective Group II mGlu receptor agonist 2 R,4 R-4-aminopyrrolidine-2,4-dicarboxilate (2 R,4 R-APDC), induced pressor effects at a dose of 300 nmol only. The compounds (150-600 nmol) did not modify the heart rate in these experiments. On the other hand, low doses of Group II mGlu receptor agonists (75 nmol 2 R,4 R-APDC; 1.5 nmol 2 S,2' R,3' R)-2-(2',3'-dicarboxychloropropyl)glycine; DCG IV) induced hypotension and bradycardia when spinal N-methyl- D-aspartate (NMDA) receptors were previously blocked by 2-amino-5-phosphonovaleric acid (APV; 30 nmol; i.t.). The pressor response to trans-ACPD was probably mediated by activation of both Group I and Group II mGluRs because i.t. injection of either the selective Group I mGlu receptor antagonist ( S)-4-carboxyphenylglycine (4CPG) or the selective Group II mGlu receptor antagonist (2 S,3 S,4 S)-2-methyl-2-(carboxycyclopropyl)glycine (MCCG) antagonized the increases in the blood pressure produced by the agonist. Moreover, 4CPG and MCCG antagonized the pressor effects of 3,5-DHPG and 2 R,4 R-APDC, respectively. Blockade of spinal Group II mGlu receptors by MCCG also prevented the hypotensive and bradycardic effects of 2 R,4 R-APDC and DCG IV in rats pretreated with APV. On the other hand, the pressor response to L-AP4 (300 nmol) was prevented by the selective antagonist ( S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4).These results suggest that activation of spinal Group I, II and III mGlu receptors increases the mean blood pressure in pentobarbital anesthetized rats and that, after blockade of NMDA receptors, low doses of Group II mGlu receptor agonists induce hypotension and bradycardia.
Celuch
Stella Maris
SM
Instituto de Investigaciones Farmacológicas (CONICET), Junín 956, 5 piso, 1113 Buenos Aires, Argentina. sceluch@ffyb.uba.ar
García
María del Carmen
Mdel C
D000759:Adjuvants, Anesthesia / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002319:Cardiovascular System / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007278:Injections, Spinal; D010424:Pentobarbital / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
D000759:Adjuvants, Anesthesia; D018094:Receptors, Metabotropic Glutamate; D010424:Pentobarbital