Selective ablation of TRPV1 by intrathecal injection of resiniferatoxin in rats increases renal sympathoexcitatory responses and salt sensitivity
Abstract
This study tested the hypothesis that selective ablation of transient receptor potential vanilloid type 1 (TRPV1)-positive nerve fibers by intrathecal injection of resiniferatoxin (RTX) enhances renal sympathoexcitatory responses and salt sensitivity. Intrathecal injection of RTX (1.8 μg/kg) to the levels of lower thoracic and upper lumbar spinal cord (T8-L3) increased mean arterial pressure (MAP) in rats fed a normal (NS, 1% NaCl) or high-sodium (HS, 8% NaCl) diet for 4 weeks compared to vehicle-treated rats (NS: 121 ± 2 vs. 111 ± 2; HS: 154 ± 2 vs. 134 ± 2 mm Hg, both P < 0.05), with a greater increase in HS compared to NS rats (9 ± 1% vs. 15 ± 1%, P < 0.05). TRPV1 contents were decreased in T8-L3 segments of spinal dorsal horn but not in corresponding dorsal root ganglia and the kidney following RTX treatment (P < 0.05). Selective activation of GABA-A receptors with intrathecal T8-L3 segment-injection of muscimol (3 nmol/kg) decreased renal sympathetic nerve activity and increased urinary excretion in both NS and HS rats, with a greater effect in RTX-treated compared to vehicle-treated rats (P < 0.05). Chronic activation of GABA-A receptors with muscimol (50 mg/kg/day × 2, p.o.) abolished RTX treatment-induced pressor effect...Continue Reading
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