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

Lin HH, Cheng TT, Lo H, Lin YC, Lai CC.

Alcohol (2018)

Intake of ethanol (alcohol) can effect many physiological functions, including cardiovascular function. Ingestion of large amounts of ethanol can cause tachycardia, vasodilation, and hypotension in humans. Glutamate and GABA receptors in the central nervous system are the targets of ethanol. These two neurotransmitters regulate the pre-sympathetic nerves in the rostral ventrolateral medulla (RVLM). Nitric oxide is also a molecule used to send messages and ethanol effects its production through the enzymes producing it, nitric oxide synthase (NOS). This study shows that ethanol acting on glutamatergic NMDA receptors and nitric oxide signaling in the RVLM plays an important role in its hypotensive effects.

The rat microinjections of nitric oxide synthase (NOS) inhibitors or NMDA receptor blockers was done by injecting a micropipette with micosyringes into the left and right RVLM. The first injections were given to conscious rats. SHRs exhibited a significantly higher blood pressure compared to the normotensive wild type rats. An injection of a lower dose of ethanol produced a decrease in systolic blood pressure (SBP) and diastolic blood pressure (DBP) in spontaneously hypertensive rats (SHRs), but did not produce any differences in normotensive rats, or wild type. The decrease in BP continues for 30 minutes after the injection and the effects lasted over 90 minutes in the SHRs. When a higher dose of ethanol was injected, even more decreases in SBP and DBP was shown in both wild type and SHRs.

The second group to receive injections were under urethane anesthesia. The lower dose of ethanol caused a decrease in SBP about 60 minutes after injection in SHRs, but did not exhibit significant changes in DBP for SHRs. The wild type rats did not show a significant change in BP when given the lower dose. The higher dose of ethanol did result in significant decreases in BP in both wild type and SHRs, although the decrease occurred much earlier in SHRs. These deceased effects occurred both early around 15 minutes and late around 45-60 minutes after the injection in wild type and SHRs.

Microinjections of L-NNA, which is a competitive NOS inhibitor, into the RVLM showed no significant changes in BP 15-60 minutes after injection in wild type and SHRs. A small dose of L-NNA injected into the RVLM 5 minutes after ethanol showed no significant effects on BP, but a higher dose significantly reduced the ethanol induced decreased in SHRs but not wild type. Ethanol induced decreases in SBP and DBP in SHRs were also blocked when the RVLM was given a NOS inhibitor or NMDA receptor antagonists. Microdialysis was then used to determine how much nitric oxide is released. This was done by measuring the amount of nitrite and glutamate in the RVLM after an injection of ethanol in wild type and SHRs. The ethanol caused a significant increase in nitrite and glutamate released in SHRs, but no significant change in wild types.

This study showed that SHRs have a high sensitivity to ethanol induced hypotensive effects and suggests that the NMDA receptors and nitric oxide system is the mechanism in the RVLM that is involved. The researchers did mention possible problems with their experiment, one being how anesthetics do affect blood pressure. It was also mentioned that since ethanol is widely distributed throughout the body after application, it may have effects on other cardiovascular mechanisms.

Paul M