Selective ablation of TRPV1 by intrathecal injection of resiniferatoxin in rats will increase renal sympathoexcitatory responses and salt sensitivity.
Hypertens Res. 2018 Jul 13;:
Authors: Yu SQ, Ma S, Wang DH
This examine examined the speculation that selective ablation of transient receptor potential vanilloid kind 1 (TRPV1)-positive nerve fibers by intrathecal injection of resiniferatoxin (RTX) enhances renal sympathoexcitatory responses and salt sensitivity. Intrathecal injection of RTX (1.eight??g/kg) to the degrees of decrease thoracic and higher lumbar spinal wire (T8-L3) elevated imply arterial strain (MAP) in rats fed a traditional (NS, 1% NaCl) or high-sodium (HS, eight% NaCl) weight loss program for four weeks in comparison with vehicle-treated rats (NS: 121?±?2 vs. 111?±?2; HS: 154?±?2 vs. 134?±?2?mm?Hg, each P?<?zero.05), with a better enhance in HS in comparison with NS rats (9?±?1% vs. 15?±?1%, P?<?zero.05). TRPV1 contents have been decreased in T8-L3 segments of spinal dorsal horn however not in corresponding dorsal root ganglia and the kidney following RTX therapy (P?<?zero.05). Selective activation of GABA-A receptors with intrathecal T8-L3 segment-injection of muscimol (three?nmol/kg) decreased renal sympathetic nerve exercise and elevated urinary excretion in each NS and HS rats, with a better impact in RTX-treated in comparison with vehicle-treated rats (P?<?zero.05). Power activation of GABA-A receptors with muscimol (50?mg/kg/day?×?2, p.o.) abolished RTX treatment-induced pressor results in NS and HS rats. GAD65/67, a GABA synthetase, within the spinal wire was downregulated and tyrosine hydroxylase within the kidney upregulated in NS or HS rats handled with RTX (P?<?zero.05). Thus, selective ablation of TRPV1-positive central terminals of sensory neurons performs a prohypertensive position probably through inhibition of spinal GABA system particularly with HS consumption, suggesting that activation of TRPV1 in central terminals of sensory neurons might convey an antihypertensive impact.
PMID: 30006640 [PubMed – as supplied by publisher]