Effect of MK-801, an antagonist of NMDA receptor in the pedunculopontine tegmental nucleus, on cardiovascular parameters in normotensive and hydralazine hypotensive rats.

OBJECTIVES

In the present study, the cardiovascular effects of glutamate NMDA receptor of the pedunculopontine tegmental nucleus (PPT) in normotensive and hydralazine (HLZ) hypotensive rats were evaluated.

MATERIALS AND METHODS

In the normotensive condition, MK-801(1 nmol; an NMDA receptor antagonist) and L-glutamate (L-Glu, 50 nmol an agonist) alone and together were microinjected into the nucleus using a stereotaxic device. In hypotensive condition, 2 min after induction of hypotension by HLZ (10 mg/kg, intravenous), drugs, same as in normotensive condition, were microinjected into the PPT. Recorded mean arterial pressure (MAP), systolic blood pressure (SBP), and heart rate (HR) were recorded throughout the experiment by a Power lab apparatus that was connected to a catheter inserted into the femoral arty. The cardiovascular changes (Δ) induced by microinjection drugs were computed and statistically analyzed.

RESULTS

In the normotensive condition, L-Glu significantly increased ΔMAP and ΔSBP (<0.001) and decreased ΔHR (<0.01) compared with the control. MK-801 alone significantly increased HR (<0.05) while co-injected with L-Glu + MK-801 it significantly attenuated the L-Glu effect on ΔMAP and ΔSBP but augmented ΔHR (<0.01). In the hydralazine hypotension condition, L-Glu significantly improved hypotension (<0.01) and deteriorated bradycardia induced by HLZ (<0.05). MK-801 alone did not significantly affect ΔMAP, ΔSBP, and ΔHR but when co-injected with L-Glu (L-Glu + MK-801) it could significantly attenuate the cardiovascular effect of L-Glu in the PPT.

CONCLUSION

We found that activation of NMDA receptors of the glutamatergic system in the PPT evoked blood pressure and inhibited HR in both normotensive and hypotensive conditions in rats.