Blockade of N-methyl-D-aspartate receptors within the rostral ventrolateral medulla antagonizes clonidine-induced cardiovascular effects.
There is wide agreement that the rostral ventrolateral medulla (RVLM) plays a crucial role in the regulation of blood pressure (BP), and that there may be a close correlation between the actions of centrally acting antihypertensive agents and N-methyl-D-aspartate (NMDA) receptor functional states. The present study was done to test the hypothesis that NMDA receptors within the RVLM were involved in the cardiovascular effects of centrally acting antihypertensive drug clonidine in anesthetized and paralyzed rats. Prior unilateral microinjection of NMDA receptor antagonist dizocilpine (MK801, 500 pmol) into the RVLM significantly attenuated (p<0.01, n=9) the reductions of BP (-24+/-6 to -8+/-4 mm Hg) and heart rate (-49+/-9 to -14+/-7 bpm) induced by unilaterally injected clonidine (5 nmol) into the RVLM. Prior bilateral microinjection of MK801 (500 pmol for each side) into the RVLM effectively (p<0.01, n=7) antagonized the hypotension (-25+/-5 to -8+/-2 mm Hg) and bradycardia (-43+/-7 to -11+/-4 bpm) of intravenously administered clonidine (10 microg kg(-1)). Importantly, iontophoretic application of MK801 (60 nA) significantly (p<0.01, n=9) prevented the inhibitory effect of intravenously (10 microg kg(-1)) injected clonidine on the discharge of presympathetic neurons in the RVLM (neuronal inhibition: -39+/-6 to -10+/-2%). In conclusion, the present study shows that the RVLM administrated MK801 effectively antagonizes clonidine-induced cardiovascular effects, and suggests that NMDA receptors within the RVLM contribute to clonidine actions.
Wang
Wei-Zhong
WZ
Department of Physiology, Second Military Medical University, 800 Xiang-Yin Road, 200433, Shanghai, China
Yuan
Wen-Jun
WJ
Su
Ding-Feng
DF
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D007478:Iontophoresis; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D003000:Clonidine