Effects of NKH477 on renal nerve stimulation-induced responses in anesthetized dogs.
We evaluated the effects of an adenylate cyclase activator, N, N-dimetyl-beta-alanine[3R-(3alpha,4alphabeta,5beta+ ++,6beta,6aalpha, 10alpha,10abeta,10balpha)]-5(acetyloxy)-3-eth enyldodecahydro-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.
Tanahashi
M
M
Laboratory of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Hara
S
S
Saitoh
K
K
Yoshida
M
M
Suzuki-Kusaba
M
M
Hisa
H
H
Satoh
S
S
D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D000758:Anesthesia; D000818:Animals; D005576:Colforsin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D020536:Enzyme Activators / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000294:innervation; D009638:Norepinephrine / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine; D014563:Urodynamics / Q000187:drug effects
D020536:Enzyme Activators; D005576:Colforsin; D012964:Sodium; D000262:Adenylyl Cyclases; D009638:Norepinephrine