Role of endogenous endothelin and nitric oxide in tubuloglomerular feedback.
To elucidate the roles of endogenous endothelin (ET) and nitric oxide (NO) in tubuloglomerular feedback (TGF), the effects of FR139317, a specific ET-A receptor antagonist, and NG-nitro-L-arginine (L-NNA), a NO synthase inhibitor on TGF were studied in Sprague-Dawley rats. FR139317 (1.5 mg/kg/hr i.v.) reversed the systemic pressor and renal vasoconstrictor responses induced by ET-1 (2 nmol/kg/hr i.v.), but did not alter the early proximal flow rate (EPFR) reduction in response to a loop perfusion with an artificial tubular fluid at 40 nl/min (47 +/- 3 vs. 47 +/- 3% in controls). L-NNA (0.2 mg/kg + 2 micrograms/kg/min i.v.) had no effect on systemic blood pressure (BP), renal hemodynamics or EPFR measured at zero perfusion (31 +/- 2 vs. 31 +/- 2 nl/min in controls), but enhanced the EPFR reduction during loop perfusion to 77 +/- 3%. Loop perfusion with 10(-3) M L-NNA in perfusate also increased the EPFR reduction to 70 +/- 7%. In conclusion, inhibition of NO synthesis enhances the TGF-mediated reduction of nephron GFR. This indicates an active participation of endogenous NO in the control of afferent arteriolar tone. endogenous ET does not influence TGF via the ET-A receptor.
Kawabata
M
M
Fourth Department of Internal Medicine, Shimane Medical University, Japan.
Han
W H
WH
Ise
T
T
Kobayashi
K
K
Takabatake
T
T
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005246:Feedback / Q000502:physiology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001381:Azepines; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D004791:Enzyme Inhibitors; D007211:Indoles; C079574:FR 139317; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase