Gastric leptin plays a role in sympathetic vasomotor control via a CCK1 receptor‐dependent mechanism

Abstract

Gastric‐derived leptin acts on vagal afferents and interacts with the gastrointestinal hormone cholecystokinin (CCK). This study aimed to examine the significance of these signals in cardiovascular regulation. The effect of CCK (4 μg/kg, i.v.) and close arterial (c.a.; coeliac) infusion of leptin (15 μg/kg) on (a) arterial pressure (AP) and heart rate (HR), (b) firing rate (FR) of presympathetic vasomotor rostroventrolateral medullary (RVLM) neurons, and (c) splanchnic/lumbar sympathetic nerve discharge (SSND/ LSND), was examined in anesthetised, male SD rats. Within 5 minutes, c.a. leptin reduced the FR of CCK‐inhibited RVLM neurons (‐28 + 5 %; P < 0.01; n=10) but not CCK‐insensitive/activated neurons (8 + 6 %; n=6), compared to saline controls (‐1 + 2 %; n=11); i.v. leptin did not affect CCK‐inhibited neurons (2 + 4 %; n=5). Leptin (c.a.) significantly decreased AP (‐13 + 3 mmHg; P < 0.05; n=16) compared to c.a. saline (‐4 + 1 mmHg; n=11) and i.v. leptin (3 + 2 mmHg; n=5) without affecting HR. The CCK1 receptor antagonist lorglumide (10 mg/kg; i.v.) abolished leptin's inhibitory effect on RVLM neurons (n=3, P < 0.05). In separate experiments c.a. leptin inhibited SSND (‐9 + 2 %; P < 0.05; n=7) compared to c.a. saline (2 + 3 %; n=5); LSND was unaffected. We conclude that leptin acting within the gut may exert selective sympathetic effects via a CCK1 receptor‐dependent mechanism that may involve the release of CCK.