Bombesin-like receptor 3 regulates blood pressure and heart rate via a central sympathetic mechanism

Abstract

Lateef DM, Xiao C, Brychta RJ, Diedrich A, Schnermann J, Reitman ML. Bombesin-like receptor 3 regulates blood pressure and heart rate via a central sympathetic mechanism. Am J Physiol Heart Circ Physiol 310: H891-H898, 2016. First published January 22, 2016; doi:10.1152/ajpheart.00963.2015.-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 ␣ 2-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.bombesin-like receptor 3; blood pressure; heart rate; sympathetic nervous system; energy metabolism NEW & NOTEWORTHY MK-5046, a bombesin-like receptor 3 (BRS-3) agonist, increases heart rate and blood pressure via increased central sympathetic tone. Brs3 null mice have a reduced resting heart rate that increases disproportionately with physical activity. BRS-3 contributes to the central regulation of heart rate and blood pressure.OBESITY is strongly associated with cardiovascular risk factors, including hypertension (6). However, the mechanisms linking obesity and hypertension are not fully understood (7,44). A number of neuroendocrine systems controlling energy homeostasis also regulate blood pressure and heart rate, including leptin, the melanocortin system, and ghrelin (12, 36, 45, 48 -50). The genetic and pharmacological manipulations of these systems that reduce adiposity generally also increase blood pressure, which is undesirable in a treatment for obesity.Bombesin-like receptor 3 (BRS-3) is a G protein-coupled receptor for which the endogenous ligand is unidentified (4,21,29,33). Despite the name, BRS-3 has a low affinity for bombesin and the related molecules, neuromedin B and gastrin-releasing ...

Bombesin receptor subtype‐3‐expressing neurons regulate energy homeostasis through a novel neuronal pathway in the hypothalamus

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Bombesin-like peptides are able to affect central histamine-induced resuscitating effect in haemorrhage-shocked rats

“…Bombesin administered directly into RVLM induces increases in MAP both in normotensive and spontaneously hypertensive rats (SHR), and BIM-23127 reduces MAP and renal sympathetic nerve activity in SHR but not in normal rats [25]. On the other hand, the studies by Lateef et al [26] show an increase in sympathetic nervous system activity, with subsequent pressor and tachycardic effects, after the activation of hypothalamic BB 3 receptors. Finally, bombesin evokes a sympathoexcitatory effect at thoracic spinal segments, acting on the sympathetic preganglionic neurons in rats [27].…”