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 μM) restored the decrements in the AA diameters. In the presence of diltiazem (10 μM), 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 μM) 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 μM)-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.
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