Obesity‐induced hypertension is associated with blunted renal sympathoinhibitory responses to gastric peptides

Abstract

The gastric peptides leptin and cholecystokinin (CCK) induce vagally-mediated splanchnic sympathoinhibition, and a medium high fat diet (MHFD) attenuates this response. Our aim was to evaluate renal sympathetic nerve discharge (RSND) responses to these peptides to determine whether blunted sympathoinhibition is linked to hypertension in obesity. Male Sprague-Dawley rats were fed either a low fat diet (LFD, control; n=8) or a MHFD (n=24) for 13 weeks; the latter were grouped as obesity prone (OP; n=8) or obesity resistant (OR; n=8) based on their weight gain falling into the upper or lower tertile, respectively. RSND and arterial pressure (AP) were recorded in isoflurane-anesthetised animals. Blood was collected for determination of plasma leptin and fat pads were excised postmortem. OP rats had higher baseline AP, plasma leptin and adiposity than control/OR rats (P < 0.05 for all). Renal sympathoinhibitory responses to CCK (0.5–8 μg/kg) administered close to the celiac artery were attenuated in OP compared to control/OR animals (P < 0.05). Close arterial leptin (15 μg/kg) induced renal sympathoinhibition in controls, and this was abolished in OP animals (P < 0.01). Diet-induced obesity may be associated with altered sensitivity of vagal afferents to gastrointestinal hormones. This may lead to increased vascular resistance in the splanchnic and renal beds, possibly contributing to hypertension in obesity.