Matsuo G, Matsumura Y, Tadano K, Morimoto S
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
J Pharmacol Exp Ther. 1997 Feb;280(2):905-10.
We previously reported that endothelin (ET) may function as an inhibitory modulator of renal noradrenergic neurotransmission (Suzuki et al., J. Cardiovasc. Pharmacol. 19: 905-910, 1992). In our study, we examined the effect of sarafotoxin S6c (S6c), a selective ET(B) receptor agonist, on changes in renal function and norepinephrine overflow induced by renal nerve stimulation (RNS) in anesthetized dogs. RNS at a low frequency (0.5-2.0 Hz) caused significant decreases in urine flow, urinary excretion of sodium and fractional excretion of sodium and increased norepinephrine secretion rate, without affecting systemic and renal hemodynamics. RNS at a high frequency (2.5-5.0 Hz), which diminishes renal hemodynamics, produced more potent decreases in urine formation and increase in norepinephrine secretion rate than seen with low frequency RNS. When S6c (1 ng/kg/min) was infused intrarenally, there was a slight and transient increase in renal blood flow, and then this response was followed by a gradual reduction. S6c administration produced increase in the basal level of urine flow with no apparent effects on urinary excretion of sodium and fractional excretion of sodium. During S6c infusion, low frequency RNS-induced antidiuretic action and increase in norepinephrine secretion rate were markedly attenuated. Qualitatively, similar results were observed in the case of high frequency RNS. In addition, high frequency RNS-induced decreases in glomerular filtration rate and filtration fraction were significantly suppressed by S6c infusion. Taken together with our previous findings, it seems likely that ET plays an important role as an inhibitory modulator of renal noradrenergic neurotransmission, through ET(B) receptor mechanisms.
我们之前报道过，内皮素（ET）可能作为肾去甲肾上腺素能神经传递的抑制性调节剂发挥作用（铃木等人，《心血管药理学杂志》19:905 - 910，1992）。在我们的研究中，我们检测了选择性ET(B)受体激动剂沙拉毒素S6c（S6c）对麻醉犬肾神经刺激（RNS）诱导的肾功能变化和去甲肾上腺素溢出的影响。低频（0.5 - 2.0 Hz）的RNS导致尿流量、尿钠排泄和钠分数排泄显著降低，去甲肾上腺素分泌率增加，而不影响全身和肾血流动力学。高频（2.5 - 5.0 Hz）的RNS会降低肾血流动力学，与低频RNS相比，它对尿液生成的降低作用更强，去甲肾上腺素分泌率增加更多。当肾内输注S6c（1 ng/kg/min）时，肾血流量有轻微且短暂的增加，随后这种反应会逐渐减弱。给予S6c使尿流量的基础水平增加，对尿钠排泄和钠分数排泄无明显影响。在输注S6c期间，低频RNS诱导的抗利尿作用和去甲肾上腺素分泌率增加明显减弱。定性地说，在高频RNS的情况下也观察到了类似结果。此外，高频RNS诱导的肾小球滤过率和滤过分数降低被S6c输注显著抑制。结合我们之前的研究结果，ET似乎通过ET(B)受体机制作为肾去甲肾上腺素能神经传递的抑制性调节剂发挥重要作用。
