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[The in Vivo Role of Vascular Chloride Channels in the Regulation of Glomerular Hemodynamics]

S Hashimoto

Hokkaido Igaku Zasshi. 1999 Sep;74(5):387-94.

PMID: 10495853

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP54197318 R(+)-IAA-94 R(+)-IAA-94 54197-31-8 Price
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