Control of rat glomerular microcirculation by juxtaglomerular adenosine A1 receptors.
The role of adenosine A1 receptors in the glomerular microcirculation and tubuloglomerular feedback (TGF) was studied in anesthetized Sprague-Dawley rats. TGF activity was assessed as the reduction in proximal tubular stop-flow pressure (SFP) on establishing orthograde perfusion of the loop of Henle with artificial tubular fluid at 40 nl/min. Administration of a selective A1 receptor antagonist, KW-3902 (0.5 microg/kg/min i.v.), increased fractional excretion of Na (FE(Na)) 4.3-fold without changing blood pressure, glomerular filtration rate, renal plasma flow, or filtration fraction. SFP in the absence of distal flow (SFP0) increased, and TGF-mediated SFP reduction was suppressed dose dependently [by 23 +/- 2% from an SFP0 of 34 +/- 1 mm Hg, by 15 +/- 4% from 36 +/- 2 mm Hg, and by 2 +/- 1% from 39 +/- 1 mm Hg during vehicle, low- and high-dose infusions (0.5 and 5.0 microg/kg/min), respectively]. Intratubular or peritubular capillary administration of 10(-4) M KW-3902 completely suppressed TGF without affecting SFP0. TGF suppression and elevation of SFP0 during systemic A1 blockade indicated vasodilation, both in the afferent arteriole and more proximal preglomerular vessels. Inhibition of tubular Na reabsorption combined with TGF suppression allowed the marked natriuresis. TGF suppression through systemic, luminal, and peritubular application of the drug suggest that juxtaglomerular apparatus A1 receptors are important in the control of glomerular microcirculation.
Kawabata
M
M
Fourth Department of Internal Medicine, Shimane Medical University, Izumo, Japan. kawabata@shimane-med.ac.jp
Ogawa
T
T
Takabatake
T
T
D000818:Animals; D004232:Diuretics / Q000494:pharmacology; D007606:Juxtaglomerular Apparatus / Q000737:chemistry* / Q000502:physiology; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000502:physiology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D014563:Urodynamics / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology
D004232:Diuretics; D018047:Receptors, Purinergic P1; D014970:Xanthines; C073525:rolofylline