Cardiovascular effects of NMDA and MK-801 infusion at area postrema and mNTS in rat

Abstract

In urethane-anesthetized male Sprague-Dawley rats, microinfusion of N- methyl- D -aspartate (NMDA) into the area postrema (AP) at the dose of 10 ng produced significant decreases in mean arterial pressure (MAP) (−26 ± 5 mmHg), heart rate (HR) (−34 ± 6 bpm), renal blood flow, mesenteric blood flow, and iliac vascular resistance. In addition, microinfusion of the same dosage of NMDA into the medial nucleus tractus solitarius (mNTS) produced significant decreases in MAP (−33 ± 4 mmHg), HR (−33 ± 6 bpm), renal blood flow, mesenteric blood flow and vascular resistance, and iliac blood flow and resistance. MK-801 (dizocilpine) microinfusion alone produced no significant changes in MAP or HR when microinfused either into the AP or unilaterally into the mNTS; however, bilateral microinfusion of MK-801 into mNTS produced sustained hypertension and tachycardia, lasting about 30 min. MK-801 pretreatment at both AP and mNTS effectively blocked NMDA-induced cardiovascular responses. MK-801 microinfusion at AP significantly attenuated baroreceptor reflex-mediated bradycardia elicited by intravenous injection of phenylephrine, but did not alter reflex tachycardia elicited by intravenous nitroprusside. In conclusion, NMDA receptor-mediated neurotransmission is involved in the cardiovascular functions of both AP and mNTS. Both loci appear to be sites of action for mK-801.