Effects of sarafotoxin S6c on antidiuresis and norepinephrine overflow induced by stimulation of renal nerves in anesthetized dogs.
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.
Matsuo
G
G
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
Matsumura
Y
Y
Tadano
K
K
Morimoto
S
S
D000768:Anesthesia, General; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D008297:Male; D009638:Norepinephrine / Q000652:urine*; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine; D013564:Sympathetic Nervous System / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014757:Viper Venoms / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; D012964:Sodium; D009638:Norepinephrine