Abstract 9101: RVLM Microinjection to Explain the Role of Metabotropic Glutamate Receptors in the Regulation of Baseline Blood Pressure and Heart Rate in SHRSP

Abstract

Introduction: Glutamate (Glu) is activated by the stimulation of its receptors. The microinjection of Glu in rostral ventrolateral medulla (RVLM) elicited a rapid and large increase in blood pressure (BP) and heart rate (HR), which is inhibited with kynurenic acid (KYN), a selective inhibitor of ionotropic glutamate receptors (iGluR). Further, we showed that the response to Glu was much greater in stroke-prone spontaneously hypertensive rats (SHRSP) than that in Wistar Kyoto (WKY) rats, indicating that iGluR in RVLM played an important role to maintain high BP & HR in SHRSP. Whereas, the role of metabotropic glutamate receptors (mGluR) in RVLM were not fully elucidated in SHRSP yet. Hypotheses: Since the different mGluR types, e.g., group I (mGluR1, mGluR5), group II (mGluR2, mGluR3) & group III (mGluR4, mGluR6, mGluR7, mGluR8), are expressed in the various regions of rat’s brain, and several studies reported that mGluR5 is largely expressed in RVLM of rats; in this study we evaluated the pathophysiological role(s) of mGluR5, expecting that mGluR5 in RVLM keeps high baseline (i) BP and (ii) HR in SHRSP. Method: MTEP (10 nmole, a highly selective mGluR5 antagonist) and KYN (4 nmole) were microinjected unilaterally in RVLM in SHRSP (n=10) and WKY (n=10) to determine the effects on baseline BP & HR. In addition, the effects of two inhibitors on response to Glu (5 nmole) microinjection were observed. Results: MTEP reduced baseline BP & HR significantly in SHRSP when compared to those in WKY (ΔMAP: -30±3 vs. -3±2 mmHg, ΔHR: -35±3 vs. -4±2 bpm, respectively, p< 0.05), but failed to attenuate a response to Glu microinjection. In contrast, KYN had no significant effects on baseline BP & HR in the two strains, whereas it showed an inhibitory effect on the response to microinjected Glu, which was significantly greater in SHRSP than that in WKY. Conclusions: This study suggested that mGluR5 in RVLM played a major role in the maintenance of high baseline BP & HR in SHRSP.