title: Somatostatin 2A receptor-expressing presympathetic neurons in the rostral ventrolateral medulla maintain blood pressure.
abstract: Bulbospinal neurons in the rostral ventrolateral medulla (RVLM) are critical for the maintenance of sympathetic vasomotor tone and normal cardiovascular reflex function. So far, selectively eliminating/inhibiting distinct subpopulations of RVLM neurons has not significantly altered arterial pressure. Here we show that RVLM presympathetic neurons that express somatostatin 2A receptors are essential for maintaining and potentially generating sympathetic vasomotor tone. Combined immunocytochemistry and in situ hybridization were used to map the expression of somatostatin receptors 1, 2A, 2B, 3, and 4 (sst1 through 4, respectively) in the rat RVLM. sst1 and sst2B were absent; sst3 and sst4 were sparse. However, sst2A was found postsynaptically and detected in 35+/-5% of bulbospinal RVLM neurons a population that included 54+/-4% of catecholaminergic and 30+/-3% of enkephalinergic neurons. Bilateral microinjection into the RVLM of either somatostatin or the receptor-selective agonist lanreotide evoked dramatic, dose-dependent sympathoinhibition, hypotension, and bradycardia that were blocked by the sst2 receptor antagonist BIM-23627 in anesthetized rats. Bilateral RVLM microinjection of somatostatin also attenuated chemoreceptor and somatosympathetic reflex function. Somatostatin only eliminated the first sympathoexcitatory peak evoked by somatosympathetic reflex activation, whereas muscimol abolished both excitatory peaks providing functional evidence that the activity of only a subpopulation of RVLM presympathetic neurons is inhibited by somatostatin. We suggest that the subpopulation of bulbospinal RVLM neurons that expresses the sst2A receptor sets sympathetic vasomotor output. These neurons are essential for maintaining resting blood pressure under anesthesia and contribute to adaptive reflexes mediated through the RVLM.
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, New South Wales, Australia.
authors.forename: Peter G R
authors.initials: PG
authors.lastname: Burke
authors.forename: Qun
authors.initials: Q
authors.lastname: Li
authors.forename: Monique L
authors.initials: ML
authors.lastname: Costin
authors.forename: Simon
authors.initials: S
authors.lastname: McMullan
authors.forename: Paul M
authors.initials: PM
authors.lastname: Pilowsky
authors.forename: Ann K
authors.initials: AK
authors.lastname: Goodchild
mesh_terms: D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D009433:Neural Inhibition / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D012584:Sciatic Nerve / Q000502:physiology; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D013119:Spinal Cord Injuries; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
chemical_list: C452813:BIM 23627; D010455:Peptides; D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; C106140:somatostatin receptor sst2A; C060347:lanreotide; D013004:Somatostatin