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

Joen Steendahl, Charlotte Mehlin Sørensen, Max Salomonsson, N.-H. Holstein-Rathlou

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Abstract

The aim of the present study was to investigate the role of Ca2+-activated Cl- 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. Ratiometric photometry of fura 2 fluorescence was used to estimate intracellular free Ca2+ concentration ([Ca2+]i) in isolated preglomerular vessels from rat kidneys. 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 10-6 M) to the isolated preglomerular vessels caused a prompt increase in [Ca2+]i. Renal preinfusion of DIDS (0.6 and 1.25 micromol/min) attenuated the ANG II-induced vasoconstriction to approximately 35% of the control response, whereas the effects of NE were unaltered. Niflumic acid (0.14 and 0.28 micromol/min) and 2-[(2-cyclopentenyl-6,7-dichloro-2,3-dihydro-2-methyl-1-oxo-1H-inden-5-yl)oxy]acetic acid (IAA-94; 0.045 and 0.09 micromol/min) did not affect the vasoconstrictive responses of these compounds. Pretreatment with niflumic acid (50 microM) or IAA-94 (30 microM) for 2 min 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 Ca2+-activated Cl- channels play a crucial role in the hemodynamic effects of ANG II and NE in rat renal vasculature.
Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume286
Issue number2
Pages (from-to)F323-30
ISSN0363-6127
DOIs
Publication statusPublished - 2003

Bibliographical note

Keywords: 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; Angiotensin II; Animals; Antihypertensive Agents; Calcium; Chloride Channels; Cyclooxygenase Inhibitors; Diuretics; Fluorescent Dyes; Fura-2; Glycolates; Kidney Glomerulus; Magnetics; Male; Niflumic Acid; Norepinephrine; Prazosin; Rats; Rats, Sprague-Dawley; Renal Circulation; Vasoconstrictor Agents

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