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Am J Physiol Renal Physiol (September 23, 2003). doi:10.1152/ajprenal.00017.2003
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Submitted on January 14, 2003
Accepted on September 11, 2003

Effects of chloride channel blockers on rat renal vascular responses to angiotensin II and norepinephrine

Joen Steendahl1, Niels-Henrik Holstein-Rathlou1, Charlotte Mehlin Sorensen1, and Max Salomonsson1*

1 Department of Medical Physiology, Division of Renal and Cardiovascular Research, The Panum Institute, University of Copenhagen, Copenhagen, Denmark

* To whom correspondence should be addressed. E-mail: maxsalomon{at}mfi.ku.dk.

The aim of the present study was to investigate the role of calcium activated chloride (ClCa) channels in the renal vasoconstriction elicited by angiotensin II (Ang II) and norepinephrine (NE). Renal blood flow (RBF) was measured in vivo using electromagnetic flowmetry. Intracellular free calcium concentration ([Ca2+] i) was estimated in isolated preglomerular vessels from rat kidneys utilizing ratiometric photometry of fura-2 fluorescence. Renal arterial injection of Ang II (2-4 ng) and NE (20-40 ng) produced a transient decrease in RBF. Administration of Ang II (10-7 M) and NE (5 x 10-6M) to the isolated preglomerular vessels caused a prompt increase in [Ca2+]i. Renal preinfusion of 4,4' diisothiocyanostilbene 2,2'-disulfonic acid (DIDS) (0.6 and 1.25 µmol/min) attenuated the Ang II induced vasoconstriction to ~35 % of the control response while the effects of NE was unaltered. Niflumic acid (0.14 and 0.28 µmol/min) and 2-[(2-cyclopentenyl-6,7dichloro-2,3-dihydro-2-methyl-1-oxo-1H-inden-5-yl)oxy]acetic acid (IAA-94) (0.045 and 0.09 µmol/min) did not affect the vasoconstrictive responses of these compounds. Two min of niflumic acid (50 µM) or IAA-94 (30 µM) pretreatment decreased baseline [Ca2+]i, but did not change the magnitude of the [Ca2+]i response to Ang II and NE in the isolated vessels. The present results do not support the hypothesis that ClCa channels play a crucial role for the hemodynamic effects of Ang II and NE in rat renal vasculature.




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