Mechanism of Peripheral NMDA Receptor‐Mediated Pressor Response in Conscious Rats

Abstract

Despite its expression in vascular and cardiac tissues, the role of peripheral NMDARs in blood pressure control in conscious animals has not been examined. This study is the first to report a dose (125, 250, 500 and 1000 μg/kg)‐related pressor response elicited by systemic NMDA in male Sprague‐Dawley rats. Femoral vessels were catheterized 2 days prior to NMDA injection and NMDA was administered i.v. at 15 min intervals (n=6). In a subsequent experiment, we tested the hypothesis that an NMDA‐evoked generation of vascular reactive oxygen species (ROS) underlies the pressor response. A submaximal dose (250 μg/kg) of NMDA or its vehicle (saline) was administered i.v. in 2 groups of conscious rats and vascular (aorta) and cardiac tissues were collected at the conclusion of the experiment. The NMDA‐treated group displayed a significant increase in MAP when compared to the control group (n=8 each, p<0.05). Tissue ROS and NO levels were analyzed using dihydroethidium (DHE) and 4‐amino‐5‐methylamino‐2′7′‐dichlorofluoroscein diacetate (DAF‐FM) fluorometry. The pressor response elicited by peripheral NMDAR activation was associated with elevated vascular ROS. The increase in vascular ROS, which approached statistical significance when compared with control values, seems to support the tested hypothesis. Interestingly, however, vascular NO was increased significantly by peripheral NMDAR activation. These findings are the first to demonstrate a peripheral NMDAR‐evoked pressor response and yield insight into possible molecular mechanisms that contribute to this response.This research was supported by East Carolina University and NIH grant R01 AA07839.