title: Effects of chloride channel blockers on rat renal vascular responses to angiotensin II and norepinephrine.
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.
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D018118:Chloride Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D006016:Glycolates / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000098:blood supply; D008280:Magnetics; D008297:Male; D009544:Niflumic Acid / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D018118:Chloride Channels; D016861:Cyclooxygenase Inhibitors; D004232:Diuretics; D005456:Fluorescent Dyes; D006016:Glycolates; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009544:Niflumic Acid; C015765:MK 473; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium; D016257:Fura-2; D009638:Norepinephrine; D011224:Prazosin