title: Commissural nucleus of the solitary tract regulates the antihypertensive effects elicited by moxonidine.
abstract: The rostral ventrolateral medulla (RVLM) contains the presympathetic neurons involved in cardiovascular regulation that has been implicated as one of the most important central sites for the antihypertensive action of moxonidine (an α2-adrenergic and imidazoline agonist). Here, we sought to evaluate the cardiovascular effects produced by moxonidine injected into another important brainstem site, the commissural nucleus of the solitary tract (commNTS). Mean arterial pressure (MAP), heart rate (HR), splanchnic sympathetic nerve activity (sSNA) and activity of putative sympathoexcitatory vasomotor neurons of the RVLM were recorded in conscious or urethane-anesthetized, and artificial ventilated male Wistar rats. In conscious or anesthetized rats, moxonidine (2.5 and 5 nmol/50 nl) injected into the commNTS reduced MAP, HR and sSNA. The injection of moxonidine into the commNTS also elicited a reduction of 28% in the activity of sympathoexcitatory vasomotor neurons of the RVLM. To further assess the notion that moxonidine could act in another brainstem area to elicit the antihypertensive effects, a group with electrolytic lesions of the commNTS or sham and with stainless steel guide-cannulas implanted into the 4th V were used. In the sham group, moxonidine (20 nmol/1 μl) injected into 4th V decreased MAP and HR. The hypotension but not the bradycardia produced by moxonidine into the 4th V was reduced in acute (1 day) commNTS-lesioned rats. These data suggest that moxonidine can certainly act in other brainstem regions, such as commNTS to produce its beneficial therapeutic effects, such as hypotension and reduction in sympathetic nerve activity.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Science, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: L T
authors.initials: LT
authors.lastname: Totola
authors.forename: T B
authors.initials: TB
authors.lastname: Alves
authors.forename: A C
authors.initials: AC
authors.lastname: Takakura
authors.forename: H C
authors.initials: HC
authors.lastname: Ferreira-Neto
authors.forename: V R
authors.initials: VR
authors.lastname: Antunes
authors.forename: J V
authors.initials: JV
authors.lastname: Menani
authors.forename: E
authors.initials: E
authors.lastname: Colombari
authors.forename: T S
authors.initials: TS
authors.lastname: Moreira
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003243:Consciousness / Q000502:physiology; D020546:Fourth Ventricle / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D019329:Idazoxan / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007267:Injections; D007276:Injections, Intraventricular; D008297:Male; D009474:Neurons / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D017552:Solitary Nucleus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D013238:Stereotaxic Techniques; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D015016:Yohimbine; C043482:moxonidine; C058525:2-methoxyidazoxan; D019329:Idazoxan
keywords: AoC; CVLM; EAA; HR; I1-R; MAP; Mean arterial pressure; NTS; PAP; RVLM; SHR; SNA; TH; TH-ir; abdominal aortic; alpha2-adrenergic receptor; caudal ventrolateral medulla; commNTS; commissural NTS; commissural nucleus of the solitary tract; excitatory amino acid; heart rate; iSNA; imidazoline receptor; integrated splanchnic nerve activity; moxonidine; nucleus of the solitary tract; pulsatile arterial pressure; rostral ventrolateral medulla; sSNA; splanchnic sympathetic nerve activity; spontaneously hypertensive rat; sympathetic activity hypertension; sympathetic nerve activity; tyrosine hydroxylase; tyrosine hydroxylase-immunoreactive; α2-AR