title: Dysglycemia induces abnormal circadian blood pressure variability.
abstract: BACKGROUND
  Prediabetes (PreDM) in asymptomatic adults is associated with abnormal circadian blood pressure variability (abnormal CBPV).
  
  
  OBJECTIVE
  Systemic inflammation and glycemia influence circadian blood pressure variability.
  
  
  METHODS
  Dahl salt-sensitive (S) rats (n = 19) after weaning were fed either an American (AD) or a standard (SD) diet. The AD (high-glycemic-index, high-fat) simulated customary human diet, provided daily overabundant calories which over time lead to body weight gain. The SD (low-glycemic-index, low-fat) mirrored desirable balanced human diet for maintaining body weight. Body weight and serum concentrations for fasting glucose (FG), adipokines (leptin and adiponectin), and proinflammatory cytokines [monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α)] were measured. Rats were surgically implanted with C40 transmitters and blood pressure (BP-both systolic; SBP and diastolic; DBP) and heart rate (HR) were recorded by telemetry every 5 minutes during both sleep (day) and active (night) periods. Pulse pressure (PP) was calculated (PP = SBP-DBP).
  
  
  RESULTS
  [mean(SEM)]: The AD fed group displayed significant increase in body weight (after 90 days; p < 0.01). Fasting glucose, adipokine (leptin and adiponectin) concentrations significantly increased (at 90 and 172 days; all p < 0.05), along with a trend for increased concentrations of systemic pro-inflammatory cytokines (MCP-1 and TNF-α) on day 90. The AD fed group, with significantly higher FG, also exhibited significantly elevated circadian (24-hour) overall mean SBP, DBP, PP and HR (all p < 0.05).
  
  
  CONCLUSIONS
  These data validate our stated hypothesis that systemic inflammation and glycemia influence circadian blood pressure variability. This study, for the first time, demonstrates a cause and effect relationship between caloric excess, enhanced systemic inflammation, dysglycemia, loss of blood pressure control and abnormal CBPV. Our results provide the fundamental basis for examining the relationship between dysglycemia and perturbation of the underlying mechanisms (adipose tissue dysfunction induced local and systemic inflammation, insulin resistance and alteration of adipose tissue precursors for the renin-aldosterone-angiotensin system) which generate abnormal CBPV.
authors: Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.
authors: Sivarajan
authors: S
authors: Kumarasamy
authors: Kathirvel
authors: K
authors: Gopalakrishnan
authors: Dong Hyun
authors: DH
authors: Kim
authors: Nader G
authors: NG
authors: Abraham
authors: William D
authors: WD
authors: Johnson
authors: Bina
authors: B
authors: Joe
authors: Alok K
authors: AK
authors: Gupta
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure; D018660:Blood Pressure Monitoring, Ambulatory; D018932:Chemokine CCL2 / Q000097:blood; D002940:Circadian Rhythm; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D006339:Heart Rate; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000097:blood; D020738:Leptin / Q000097:blood; D011236:Prediabetic State / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D051381:Rats; D020303:Rats, Inbred Dahl; D013686:Telemetry; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015430:Weight Gain
chemical_list: D052242:Adiponectin; C499920:Adipoq protein, rat; D015415:Biomarkers; D001786:Blood Glucose; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha