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Attenuated cardiovascular‐renal sensitivity of blood pressure and heart rate to infused insulin in obese TallyHo/Jng mice
Author(s) -
Alunan Ashley,
Li Lijun,
Lee Hwal,
Fluitt Maurice,
Tiwari Swasti,
Ecelbarger Carolyn M.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.855.5
Subject(s) - blood pressure , medicine , endocrinology , insulin , insulin resistance , heart rate , basal (medicine) , hypoglycemia
Obese mice are known to be relatively insulin resistant with regard to cellular glucose uptake; however, it is still uncertain whether the cardiovascular‐renal system develops insulin resistance and what this means in terms of blood pressure (BP) and heart rate (HR). To address this problem, we tested the impact of pre‐existing metabolic syndrome (MetS) on BP, HR (radiotelemetry), and blood chemistry responses to an insulin infusion using a newer inbred polygenic model of MetS. Male TallyHo/Jng (TH) mice were infused with 50 U/kg bw insulin by osmotic minipump for 2‐weeks. C57Bl6 (B6) mice were used as insulin‐sensitive controls (n = 6/strain). All mice were provided with 20% glucose, 0.5% NaCl, 0.5% K 2 HPO 4 water to drink to combat hypoglycemia during the infusion. Mean arterial BP of TH mice was significantly (p < 0.05) higher than B6, e.g., 126±2 versus 112±5 mm Hg prior to infusion. Infusion led to an initial fall in BP in B6 (Day 3‐ 108±2) followed by a slow rise (Day 13‐ 122±8). In contrast BP remained fairly steady in TH (Day 3‐ 123±1; Day 13‐ 125±5). Similarly HR was elevated in TH in the basal period: 649±8 versus 527±20 beats per min, (bpm) in B6, and was reduced by insulin infusion to 614±21 (Day 13). In B6, HR rose to 563±30 (Day 13). Insulin infusion caused a number of changes in blood chemistry including, a reduction in pH and HCO 3 levels. Most of these changes were independent of strain; however, insulin infusion caused a reduction in blood glucose levels only in the B6 mice. Overall, we found greater sensitivity of BP and HR to insulin in B6 versus TH. The rise in HR with insulin is likely the result of a rise in sympathetic activity. Insulin infusion produced somewhat “beneficial” changes in TH with a slight fall in HR and BP. In contrast, in B6, after the first few days, BP and HR rose, suggesting primarily detrimental effects likely as mice developed a resistance to the infusion. These findings demonstrate that insulin resistance extends to non‐traditional target tissues in MetS; and that insulin resistance, not insulin action per se, is correlated to rises in both BP and HR during MetS. Support or Funding Information Georgetown University internal funding and Georgetown/Howard University CTSA