Effects of intracarotid injection of 17B-estradiol on electrical activity of rostral ventrolateral medullary neurons in male rats

Wang Sheng, HE Rui-Rong

Acta Physiologica Sinica, 2002

                There is a body of evidence suggesting that estrogen can modulate the neuronal control of cardiovascular parameters but it is still unknown exactly what estrogen is doing at the level of the brain. Some studies have shown increases and decreases in blood pressure depending on where the estrogen is injected suggesting that there is a complex interaction in the brain that is causing the effects of estrogen. Estrogen receptors have been localized to the rostral ventrolateral medulla (RVLM) and it is possible that these receptors are the cause of some of the effects that estrogen has on blood pressure. The purpose of the current study was to asses the effects of estrogen on electrical activity in the RVLM.

                The current study used Sprague-Dawley rats that all underwent surgical procedures that included sino-aortic denervation and procedures to allow the measurement of heart rate, blood pressure, infusion of compounds into the carotid artery as well as extracellular single-unit recordings in the RVLM. Ras were allowed to stabilize for 30 minutes after the procedures and then the microelectrode was inserted to record electrical activity from the RVLM. This study recorded spontaneous activity for 5 minutes prior to injecting drugs to have a baseline of activity to compare to. Rats were divided into four groups. Group 1 had intracarotid injection of 17B-estradiol. Group 2 had injections of 17B-estradiol before and after tamoxifen, an estrogenic antagonist. Group 3 had injections of 17B-estradiol before and after administration of N-nitro-L-arginine-methyl ester, a nitric oxide synthase inhibitor. Group 4 had injections of 17B-estradiol before and after administration of 3-morpholinosydnonimine, a nitric oxide donor. Measurements of blood pressure, heart rate, and electroneurogram of RVLM neurons was obtained in all groups.

                Injections of estrogen had an immediate (within 1 minute) and significant effect of decreasing spontaneous activity of RVLM neurons in 25 out of the 30 single unit recordings. This effect lasted greater than 5 minutes and could be repeated upon subsequent injections that occurred after a 15 minute break. Estrogen had no effect on heart rate or blood pressure. Injection of tamoxifen had no effect on its own, and injection of estrogen 30 minutes after tamoxifen had a similar significant effect of lowering spontaneous firing rate. Intracarotid injections of N-nitro-L-arginine-methyl ester markedly attenuated the effect that estrogen had on decreasing firing rate. Intracarotid injections of estrogen with 3-morpholinosydnonimine significantly reduced the electrical firing rate. There was no effect of any of the injections on heart rate or blood pressure.

                The time course of actions in the present study indicate a nongenomic action of estrogen that could be dependent on nitric oxide release. This paper was interesting in showing that estrogen can have a direct and immediate effect on the activity of the RVLM, however, even more interesting that this change in activity in the RVLM did not result in a change in blood pressure. The paper suggests that although there could (should haha) have been a decrease in vascular tone and peripheral resistance from the decrease in RVLM neuron activity, there could have also been an increase in cardiac output which balanced this to create no change in the blood pressure.

Ben R