392 OBESITY-RELATED HYPERTENSION IS ASSOCIATED WITH ALTERED SENSITIVTY OF CARDIOVASCULAR CONTROLLING NEURONS IN THE ROSTROVENTROLATERAL MEDULLA

Abstract

Background: The gut and kidneys command >50% cardiac output postprandially, highlighting the importance of blood flow regulation to these regions. The gut hormone cholecystokinin (CCK) acts at vagal afferents to induce renal and splanchnic sympathoinhibition and vasodilation, via reflex inhibition of a subclass of cardiovascular-controlling neurons in the rostroventrolateral medulla (RVLM). Since these responses are blunted in obese hypertensive rats, our aim was to determine whether this is due to altered sensitivity of RVLM neurons. Methods: Male Sprague-Dawley rats (n = 32) were placed on a medium high fat diet (MHFD; n = 24) or low fat diet (LFD, control animals; n = 8) for 15 weeks. MHFD rats were classified as obesity prone (OP; upper tertile weight gain; n = 8) or obesity resistant (OR; lower tertile weight gain n = 8). In anaesthetized, artificially ventilated animals, arterial pressure (AP) and heart rate were monitored. Electrophysiological techniques were used to identify RVLM presympathetic vasomotor neurons, and responsiveness to CCK tested (0.05 – 4ug/kg; i.a.). Results: OP animals had elevated resting AP compared to OR/control animals (P < 0.05). Barosensitivity of RVLM neurons was significantly attenuated in OP animals (P < 0.05), suggesting altered baroreflex gain. CCK-induced inhibitory responses in OR/control animals were blunted/completely reversed in OP animals. Conclusion: Obesity-related hypertension is associated with altered responsiveness of RVLM neurons, possibly leading to blunted sympathoinhibitory and vasodilator effects in the renal and splanchnic vascular beds. In obesity, dietary changes and increased heomodynamic demand to these regions, together with blunted sympathoinhibitory mechanisms, may lead to increased regional vascular resistance and contribute to the development of hypertension.