[The in vivo role of vascular chloride channels in the regulation of glomerular hemodynamics].
The calcium(Ca2+)-dependent chloride channel (CIC) may have a crucial role in the modulation of the effects of Angiotensin II (AII) on vascular smooth muscle cell and glomerular mesangium. We examined in vivo effects of a Ca(2+)-dependent chloride channel blocker, R(+)-methylindazone indanyloxy acetic acid 94 (IAA-94), on renal and glomerular hemodynamics in rats. A small needle was inserted from the kidney surface and the renal interstitium was directly perfused first with saline, control solution. For AII group, AII-concentrations were serially 10(-7) M, 10(-6) M, and 10(-5) M, and for AII and IAA-94 group, ratios of AII to IAA-94 (300 microM) the same serial concentrations. Perfusion with AII solution resulted in dose-dependent increase in renal vascular resistance (RVR), while no such elevation of RVR was observed under the perfusion with AII/IAA. To investigate the effects of Ca(2+)-dependent chloride channel on the regulatory mechanism of renal microcirculation, i.e., tubuloglomerular feed back (TGF) response, we performed micropuncture experiment. We measured proximal tubular stop-flow pressure (Psf) during the immersion of the corresponding nephron with drugs by the simultaneous perfusion of peritubular capillaries with the solutions containing AII (10(-7) M) or AII and IAA-94 (300 microM). TGF response was significantly enhanced by AII, while the increment in TGF response was completely abolished by concomitant IAA. Immersion with IAA-94 alone caused no alteration in TGF response. These data suggest that chloride channels could modulate AII action in renal and glomerular hemodynamics.
Hashimoto
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Department of Internal Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D005246:Feedback / Q000187:drug effects; D006016:Glycolates / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D018118:Chloride Channels; D006016:Glycolates; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C015765:MK 473; D002118:Calcium