Effects of uroguanylin, an intestinal natriuretic peptide, on tubuloglomerular feedback.
Uroguanylin is an endogenous peptide that stimulates cyclic guanosine monophosphate (cGMP) production via the activation of guanylate cyclase C (GC-C) in the intestine and kidney. A high salt diet, but not intravenous salt load, enhances the secretion of biologically active uroguanylin from the intestine and increases its concentration in plasma and urine. Our purpose is to clarify the effect of uroguanylin on renal microcirculation and the tubuloglomerular feedback (TGF) mechanism. Clearance and micropuncture experiments were performed in anesthetized rats. TGF responsiveness was assessed in superficial nephrons by measuring the changes of early proximal flow rate (EPFR) in response to orthograde loop perfusion at 40 nl/min with artificial tubular fluid (ATF). Reductions in EPFR induced by loop perfusion during intravenous infusion of uroguanylin at the rate of 10 and 50 nmol/kg/h were similar yet significantly less than that during the control period (33+/-3% and 35+/-3% vs. 47+/-3%, p<0.05). Intraluminal application of uroguanylin at 10(-7) and 10(-5) mol/l in ATF decreased EPFR by 40+/-3% and 33+/-7%, respectively, with the latter value being significantly less than the control (p<0.05). Intravenous infusion of uroguanylin did not significantly change whole kidney function. Administration of atrial natriuretic peptide (ANP), which activates GC-A and B, significantly suppressed TGF-mediated EPFR reduction either intravenously (10 nmol/kg/h) or intraluminally (10(-5) mol/l in ATF) (9+/-3% and 13+/-2% vs. 47+/-3% of the control, p<0.05). In conclusion, uroguanylin clearly suppresses TGF both through intravenous and intraluminal routes, although the effects on glomerular microcirculation and whole kidney function are far less than those of ANP.
Wang
Tao
T
Fourth Department of Internal Medicine, Shimane Medical University, Izumo, Japan. wangtao@shimane-med.ac.jp
Kawabata
Masahiko
M
Haneda
Manabu
M
Takabatake
Toshikazu
T
D000818:Animals; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000502:physiology; D008297:Male; D008833:Microcirculation; D009318:Natriuresis / Q000187:drug effects; D045265:Natriuretic Peptides; D010455:Peptides / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects
D045265:Natriuretic Peptides; D010455:Peptides; C084362:uroguanylin