Spontaneously hypertensive rats exhibit higher sensitivity to ethanol induced hypotensive effects: Role of NMDA receptors and nitric oxide in rostral ventrolateral medulla

摘要

Intake of ethanol (alcohol) affects cardiovascular function. Acute ethanol intake has been shown to lower blood pressure (BP) in hypertensive patients. The present study was undertaken to examine the effects and mechanisms of acute administration of ethanol on BP in hypertensive and normotensive rats. Ethanol was given by intraperitoneal (i.p.) injection in male spontaneously hypertensive rats (SHRs) and the normotensive Wistar-Kyoto rats (WKYs). BP responses were measured in free-moving conscious rats or in urethane-anesthetized rats. Inhibitors were applied by bilateral microinjection into the rostral ventrolateral medulla (RVLM). Nitric oxide (NO center dot) levels and glutamate levels were determined by nitrate and nitrite (NOx) analyzer and HPLC-ECD, respectively. Intraperitoneal (i.p.) injection of ethanol (1.6 g/kg) caused a significant decrease in BP in free-moving or in anesthetized SHRs but not in WKYs. A higher dose (3.2 g/kg) of ethanol decreased BP in both SHRs and WKYs, although the depressor responses in SHRs occurred significantly earlier than those in WKYs. The blood ethanol concentrations 60 min after injection were similar in SHRs and WKYs. Bilateral microinjection of nitric oxide synthase (NOS) inhibitors or glutamatergic NMDA receptor antagonists into the RVLM 5 min after administration of ethanol significantly inhibited the ethanol-induced depressor effects in SHRs. The levels of NOx and glutamate release in the RVLM following ethanol administration and the NOx content in the RVLM areas 30 min after administration were significantly increased in SHRs, but not in WKYs. Our results showed that SHRs were more sensitive to ethanol-induced hypotensive effects than WKYs because of augmentation of ethanol-induced expression of the glutamatergic NMDA receptor/NO center dot signal in the RVLM of SHRs. (C) 2018 Elsevier Inc. All rights reserved.