TY - JOUR
T1 - Effects of NKH477 on renal nerve stimulation-induced responses in anesthetized dogs
AU - Tanahashi, Masayuki
AU - Hara, Sunao
AU - Saitoh, Kazutomo
AU - Yoshida, Makoto
AU - Suzuki-Kusaba, Mizue
AU - Hisa, Hiroaki
AU - Satoh, Susumu
N1 - Funding Information:
NKH477 was generously provided by Nippon Kayaku, Tokyo, Japan. This work was supported in part by Grant 10557226 (to M. Yoshida) for Scientific Research from the Ministry of Education, Science and Culture, Japan.
PY - 1999/11/12
Y1 - 1999/11/12
N2 - We evaluated the effects of an adenylate cyclase activator, N,N-dimetyl-β-alanine[3R-(3α,4αβ,5β,6β,6aα,10α,10aβ,10bα)]-5(acetyloxy)-3-ethenyldodecahydro-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-1H-naphtho[2,1-b]pyran-6-yl ester hydrochloride (NKH477), on neural control of renal functions in anesthetized dogs. Renal nerve stimulation (2 Hz) increased renal norepinephrine efflux and reduced renal blood flow, glomerular filtration rate, urine flow rate, urinary Na+ excretion and fractional Na+ excretion. Intrarenal arterial infusion of NKH477 (300 ng/kg/min) suppressed the stimulation-induced reductions in renal blood flow and glomerular filtration rate and attenuated the reductions in urine flow rate and urinary Na+ excretion but not the changes in renal norepinephrine efflux and fractional Na+ excretion. Infusion of NKH477 did not affect the urinary responses induced by renal nerve stimulation at a lower frequency (0.5-1 Hz) which had little influence on renal blood flow and glomerular filtration rate. The present results demonstrate that NKH477 inhibits renal vasoconstriction and hypofiltration but not the enhanced tubular Na+ reabsorption during activation of the renal sympathetic nervous system. Copyright (C) 1999 Elsevier Science B.V.
AB - We evaluated the effects of an adenylate cyclase activator, N,N-dimetyl-β-alanine[3R-(3α,4αβ,5β,6β,6aα,10α,10aβ,10bα)]-5(acetyloxy)-3-ethenyldodecahydro-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-1H-naphtho[2,1-b]pyran-6-yl ester hydrochloride (NKH477), on neural control of renal functions in anesthetized dogs. Renal nerve stimulation (2 Hz) increased renal norepinephrine efflux and reduced renal blood flow, glomerular filtration rate, urine flow rate, urinary Na+ excretion and fractional Na+ excretion. Intrarenal arterial infusion of NKH477 (300 ng/kg/min) suppressed the stimulation-induced reductions in renal blood flow and glomerular filtration rate and attenuated the reductions in urine flow rate and urinary Na+ excretion but not the changes in renal norepinephrine efflux and fractional Na+ excretion. Infusion of NKH477 did not affect the urinary responses induced by renal nerve stimulation at a lower frequency (0.5-1 Hz) which had little influence on renal blood flow and glomerular filtration rate. The present results demonstrate that NKH477 inhibits renal vasoconstriction and hypofiltration but not the enhanced tubular Na+ reabsorption during activation of the renal sympathetic nervous system. Copyright (C) 1999 Elsevier Science B.V.
KW - Dog
KW - Glomerular filtration
KW - NKH477
KW - Renal nerve
KW - Urinary Na excretion
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U2 - 10.1016/S0014-2999(99)00654-8
DO - 10.1016/S0014-2999(99)00654-8
M3 - Article
C2 - 10611416
AN - SCOPUS:0032783789
VL - 384
SP - 31
EP - 36
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1
ER -