title: Bombesin-like receptor 3 regulates blood pressure and heart rate via a central sympathetic mechanism.
abstract: Bombesin-like receptor 3 (BRS-3) is an orphan G protein-coupled receptor that regulates energy expenditure, food intake, and body weight. We examined the effects of BRS-3 deletion and activation on blood pressure and heart rate. In free-living, telemetered Brs3 null mice the resting heart rate was 10% lower than wild-type controls, while the resting mean arterial pressure was unchanged. During physical activity, the heart rate and blood pressure increased more in Brs3 null mice, reaching a similar heart rate and higher mean arterial pressure than control mice. When sympathetic input was blocked with propranolol, the heart rate of Brs3 null mice was unchanged, while the heart rate in control mice was reduced to the level of the null mice. The intrinsic heart rate, measured after both sympathetic and parasympathetic blockade, was similar in Brs3 null and control mice. Intravenous infusion of the BRS-3 agonist MK-5046 increased mean arterial pressure and heart rate in wild-type but not in Brs3 null mice, and this increase was blocked by pretreatment with clonidine, a sympatholytic, centrally acting α2-adrenergic agonist. In anesthetized mice, hypothalamic infusion of MK-5046 also increased both mean arterial pressure and heart rate. Taken together, these data demonstrate that BRS-3 contributes to resting cardiac sympathetic tone, but is not required for activity-induced increases in heart rate and blood pressure. The data suggest that BRS-3 activation increases heart rate and blood pressure via a central sympathetic mechanism.
authors.affiliation: Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland;
authors.forename: Dalya M
authors.initials: DM
authors.lastname: Lateef
authors.affiliation: Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland;
authors.forename: Cuiying
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland;
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Brychta
authors.affiliation: Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, Tennessee; and.
authors.forename: André
authors.initials: A
authors.lastname: Diedrich
authors.affiliation: Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Schnermann
authors.affiliation: Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland; marc.reitman@nih.gov.
authors.forename: Marc L
authors.identifier: http://orcid.org/0000-0002-0426-9475
authors.initials: ML
authors.lastname: Reitman
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D006339:Heart Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D018004:Receptors, Bombesin / Q000235:genetics / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
chemical_list: D018663:Adrenergic Agents; D018004:Receptors, Bombesin; C107120:bombesin receptor subtype 3
keywords: blood pressure; bombesin-like receptor 3; energy metabolism; heart rate; sympathetic nervous system