Gastric leptin: a novel role in cardiovascular regulation

Abstract

derived leptin affects satiety and gastrointestinal function via vagal mechanisms and has been shown to interact with the gut hormone cholecystokinin (CCK). CCK selectively inhibits splanchnic sympathetic nerve discharge (SND) and the activity of a subset of presympathetic vasomotor neurons in the rostroventrolateral medulla (RVLM). The present study sought to examine the effects of gastric leptin on arterial pressure (AP), heart rate (HR), SND, and RVLM neuronal activity to determine whether its effects on cardiovascular regulation are dependent on CCK1 receptors and vagal afferent transmission. To mimic gastric leptin, leptin (15-30 g/kg) was administered close to the coeliac artery in anesthetized, artificially ventilated Sprague-Dawley rats. Within 5 min, leptin selectively decreased the activity of RVLM neurons also inhibited by CCK (Ϫ27 Ϯ 4%; P Ͻ 0.001; n ϭ 15); these inhibitory effects were abolished following administration of the CCK1 receptor antagonist lorglumide. Leptin significantly decreased AP and HR (Ϫ10 Ϯ 2 mmHg, P Ͻ 0.001; and Ϫ8 Ϯ 2 beats/min, P Ͻ 0.01; n ϭ 35) compared with saline (Ϫ1 Ϯ 2 mmHg, 3 Ϯ 2 beats/min; n ϭ 30). In separate experiments, leptin inhibited splanchnic SND compared with saline (Ϫ9 Ϯ 2% vs. 2 Ϯ 3%, P Ͻ 0.01; n ϭ 8). Bilateral cervical vagotomy abolished the sympathoinhibitory, hypotensive, and bradycardic effects of leptin (P Ͻ 0.05; n ϭ 6). Our results suggest that gastric leptin may exert acute sympathoinhibitory and cardiovascular effects via vagal transmission and CCK1 receptor activation and may play a separate role to adipose leptin in short-term cardiovascular regulation. rostroventrolateral medulla; sympathetic nerve; cholecystokinin; reflex; rat

Sites of action of ghrelin receptor ligands in cardiovascular control

“…Experiments were carried out in anesthetized and artificially ventilated male Sprague-Dawley rats (300 -400 g), as previously described (46). The jugular vein was cannulated for intravenous administration of drugs and the left carotid artery for arterial pressure (AP) and heart rate (HR) measurement.…”

“…The gut hormones, cholecystokinin and leptin, activate subdiaphragmatic vagal afferents to induce a reflex response, resulting in a lowering of blood pressure and inhibition of splanchnic sympathetic nerve activity (45,46). If ghrelin, another gut hormone, were to stimulate abdominal vagal endings, this might contribute to the lowering of blood pressure.…”

“…Thus ghrelin could lower blood pressure if it inhibited transmission from preganglionic neurons, a possibility that does not appear to have been previously investigated. Other gut-derived hormones, such as cholecystokinin and leptin, lower blood pressure by acting on afferent nerve endings (44,46). Stimulation of cardiac afferents by ghrelin has been suggested to explain how this agent prevents the rise in cardiac sympathetic nerve activity that is produced by cardiac infarction (52).…”

Synergistic effects of apelin and leptin on isolated rat pulmonary arteries

“…In vivo studies have revealed the involvement of LEP in the control of vascular tone by simultaneously producing a sympathetically mediated vasoconstriction and an endothelium-mediated vasodilation [8,9]. Depending on the experimental design or the variety of LEP used in the experiments, literature data showed that in vivo administration of LEP could increase [10], have no effect on [11], or decrease [12,13] …”

High-fat diet is associated with blunted splanchnic sympathoinhibitory responses to gastric leptin and cholecystokinin: implications for circulatory control

“…This has prompted suggestions that gastric leptin may subserve different physiological functions to those of adipose leptin (3,22,24,33,41). Although gastric leptin acts synergistically with CCK at vagal afferents to regulate food intake (3,4,23,32,33), this relationship may also be important in cardiovascular regulation (41). Leptin infusion close to the coeliac artery inhibits a subset of cardiovascular-controlling neurons in the rostroventrolateral medulla that are also inhibited by CCK and are thought to be responsible for supplying sympathetic vasomotor outflow to the gastrointestinal circulation (40 -42, 44, 45, 49).…”