Cardiovascular effects of NMDA in the RVLM of spontaneously hypertensive rats

Abstract

In this study we found that cardiovascular effects were differentially regulated by N-methyl- d-aspartate (NMDA) in the rostral ventral lateral medulla (RVLM) of spontaneously hypertensive rats (SHRs) compared to their normotensive controls (Wistar-Kyoto rats, WKYs). Adult SHRs and WKYs were anesthetized with urethane, cervically vagotomized, and placed in a sterotaxic frame. We found that electrical stimulation or local application of N-methyl- d-aspartate into the RVLM produced hypertension in both strains. Mcroinjection (3.5–4.0 nmol) of AP5 (2-amino-5-phosphono-valerate),an NMDA receptor antagonist, to the RVLM did not affect resting blood pressure; however, this agent antagonized hypertensive responses evoked by low-frequency electrical stimulation (5–20 Hz) in both strains. The elevation in blood pressure evoked by stimulation at a higher frequency (60 Hz) was not affected by AP5. These results suggest that NMDA receptors are involved in the low frequency, electrically evoked hypertension in both strains. We also found that SHRs had a larger pressor response to microinjection of NMDA and electrical stimulation than did WKYs. AP5 abolished the differences in evoked hypertension between WKYs and SHRs during low-frequency (5–10 Hz) electrical stimulation. These data suggest that the hypersensitivity of RVLM to low-frequency electrical stimulation in SHRs involve NMDA receptors. We previously reported that AP7 antagonizes NMDA and carotid clamping-induced hypertension. In this study, we found that when locally applied to RVLM, AP5 antagonized hypertension evoked by clamping the carotid arteries in SHRs and WKYs. Thus, carotid clamping-induced hypertension may also involve NMDA receptors in the RVLM. Taken together, these results suggest that NMDA receptors in the RVLM are involved in the vasomotor regulation. Furthermore, this involvement of NMDA receptors may be differentially regulated among different genetic populations, because SHRs were more sensitive to the low-frequency electrical stimulation and NMDA chemical stimulation in the RVLM than WKYs.