title: Role of chloride channels in afferent arteriolar constriction.
abstract: The effects of IAA-94, a chloride channel blocker and/or low chloride perfusate on afferent arteriolar (AA) constriction by angiotensin II (Ang II), norepinephrine (NE) and increasing pressure (80 to 160 mm Hg) were assessed using isolated perfused hydronephrotic kidneys. In the first series of experiments, Ang II (0.3 nM) constricted AAs by 33 +/- 3% (N = 5, P < 0.01). Subsequent addition of diltiazem (10 microM) restored the decrements in the AA diameters. In the presence of diltiazem (10 microM), increasing pressure did not constrict AAs. In the second series of experiments. elevation of pressure constricted AAs by 20 +/- 2% (N = 7. P < 0.01). Subsequent addition of IAA-94 (30 microM) failed to alter the basal AA diameter and myogenic responsiveness. However, Ang II-induced AA constriction was abolished by IAA-94. In the third series of experiments, decreasing extracellular chloride exaggerated AA constriction by 0.1 nM of Ang II (from 13 +/- 2 to 20 +/- 3%, N = 6, P < 0.05). Similarly, low chloride perfusate enhanced NE (0.1 microM)-induced AA constriction (from 14 +/- 2 to 19 +/- 2%, N = 6, P < 0.05). In contrast, myogenic responsiveness was not influenced by reducing chloride concentrations. The present data provide evidence that both Ang II and NE induce AA constriction by opening chloride channels and subsequent activation of voltage-dependent calcium channels, and suggest that the myogenic response is mediated by activating voltage-dependent calcium channels independently of chloride channels.
authors.affiliation: Shinjuku Suimei Clinic, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Takenaka
authors.forename: Y
authors.initials: Y
authors.lastname: Kanno
authors.forename: Y
authors.initials: Y
authors.lastname: Kitamura
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Saruta
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D006016:Glycolates / Q000494:pharmacology; D015640:Ion Channel Gating / Q000502:physiology; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D011312:Pressure; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018118:Chloride Channels; D002712:Chlorides; D004232:Diuretics; D006016:Glycolates; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C015765:MK 473; D011433:Propranolol; D004110:Diltiazem; D009638:Norepinephrine