title: 5-HT1D receptor inhibits renal sympathetic neurotransmission by nitric oxide pathway in anesthetized rats.
abstract: Although serotonin has been shown to inhibit peripheral sympathetic outflow, serotonin regulation on renal sympathetic outflow has not yet been elucidated. This study investigated which 5-HT receptor subtypes are involved. Wistar rats were anesthetized (sodium pentobarbital; 60mg/kg, i.p.), and prepared for in situ autoperfused rat kidney, which allows continuous measurement of systemic blood pressure (SBP), heart rate (HR) and renal perfusion pressure (PP). Electrical stimulation of renal sympathetic nerves resulted in frequency-dependent increases in PP (18.3±1.0, 43.7±2.7 and 66.7±4.0 for 2, 4 and 6Hz, respectively), without altering SBP or HR. 5-HT, 5-carboxamidotryptamine (5-HT1/7 agonist) (0.00000125-0.1μg/kg each) or l-694,247 (5-HT1D agonist; 0.0125μg/kg) i.a. bolus inhibited vasopressor responses by renal nerve electrical stimulation, unlike i.a. bolus of agonists α-methyl-5-HT (5-HT2), 1-PBG (5-HT3), cisapride (5-HT4), AS-19 (5-HT7), CGS-12066B (5-HT1B) or 8-OH-DPAT (5-HT1A) (0.0125μg/kg each). The effect of l-694,247 did not affect the exogenous norepinephrine-induced vasoconstrictions, whereas was abolished by antagonist LY310762 (5-HT1D; 1mg/kg) or l-NAME (nitric oxide; 10mg/kg), but not by indomethacin (COX1/2; 2mg/kg) or glibenclamide (ATP-dependent K(+) channel; 20mg/kg). These results suggest that 5-HT mechanism-induced inhibition of rat vasopressor renal sympathetic outflow is mainly mediated by prejunctional 5-HT1D receptors via nitric oxide release.
authors.affiliation: Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain.
authors.forename: José-Ángel
authors.initials: JÁ
authors.lastname: García-Pedraza
authors.affiliation: Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: García
authors.affiliation: Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain.
authors.forename: María-Luisa
authors.initials: ML
authors.lastname: Martín
authors.affiliation: Laboratorio de Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, 37007 Salamanca, Spain. Electronic address: amoran@usal.es.
authors.forename: Asunción
authors.initials: A
authors.lastname: Morán
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044346:Receptor, Serotonin, 5-HT1D / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D014363:Tryptamines / Q000494:pharmacology
chemical_list: D010069:Oxadiazoles; D011810:Quinoxalines; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D058829:Serotonin 5-HT1 Receptor Antagonists; D014363:Tryptamines; C052561:CGS 12066B; C085632:L 694247; D009569:Nitric Oxide; D012701:Serotonin; C047087:5-carboxamidotryptamine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine
keywords: 5-Carboxamidotryptamine maleate (PubChem CID: 11709509); 5-HT hydrochloride (PubChem CID: 160436); 5-HT(1D) receptor; 8-OH-DPAT hydrobromide (PubChem CID: 6917794); CGS-12066B dimaleate (PubChem CID: 56927914); Glibenclamide (PubChem CID: 3488); Indomethacin (PubChem CID: 3715); LY310762 hydrochloride (PubChem CID: 11957576); Nitric oxide; Renal vasculature; Serotonin; Sympathetic renal stimulation; l-694,247 (PubChem CID: 132059); l-NAME hydrochloride (PubChem CID: 135193)