title: Renal sympathoinhibitory and regional vasodilator responses to cholecystokinin are altered in obesity-related hypertension.
abstract: The gut and kidney command >50% of cardiac output postprandially, highlighting the importance of these vascular beds in cardiovascular homeostasis. The gastrointestinal peptide cholecystokinin (CCK) induces vagally mediated splanchnic sympathoinhibition that is attenuated in animals fed a medium high-fat diet (MHFD); therefore, our aim was to determine whether renal sympathetic nerve discharge (RSND) responses to CCK are also affected by this diet, and whether these changes are associated with obesity and hypertension. Another aim was to determine whether regional vasodilator responses to CCK are affected in obesity-related hypertension. In two separate studies, Sprague-Dawley rats were fed either a low-fat diet (LFD; control) or a MHFD for 13 weeks, after which MHFD animals were classified as obesity prone (OP) or obesity resistant (OR) based on their weight gain falling into the upper or lower tertile, respectively. Arterial pressure and heart rate were monitored in isoflurane-anaesthetized, artificially ventilated animals, and either RSND or regional vascular responses to CCK (0.1-8 μg kg(-1)) were evaluated. The OP rats had higher baseline arterial pressure compared with control/OR rats (P < 0.05). Administration of CCK inhibited RSND and increased renal vascular conductance in control/OR rats, and these responses were significantly blunted in OP rats (P < 0.05 for all). Baseline arterial pressure was positively correlated with weight gain and inversely correlated with CCK-induced vasodilatation (P < 0.05 for both). We hypothesize that in obesity-related hypertension, disruption of the sympathoinhibitory signals elicited by CCK reduces vasodilatation in the splanchnic/renal regions, leading to increased postprandial vascular resistance.
authors.affiliation: Clinical Pharmacology and Therapeutics Unit, Department of Medicine, Austin Health, Heidelberg, Victoria 3084, Australia. dsartor@unimelb.edu.au
authors.forename: Jackie M Y
authors.initials: JM
authors.lastname: How
authors.forename: Talia J
authors.initials: TJ
authors.lastname: Pumpa
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Sartor
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002766:Cholecystokinin / Q000494:pharmacology* / Q000502:physiology; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat; D006339:Heart Rate; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000294:innervation* / Q000503:physiopathology; D008297:Male; D009765:Obesity / Q000150:complications* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D002766:Cholecystokinin