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Renal denervation lowers mean arterial pressure in obese female Schlager mice but adversely affects glucose metabolism
Author(s) -
AsirvathamJeyaraj Ninitha,
Banek Christopher T,
Gauthier Madeline M,
Han Ruijun,
Razzoli Maria,
Bartolomucci Alessandro,
PanoskaltsisMortari Angela,
Osborn John W
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.720.6
Subject(s) - medicine , endocrinology , blood pressure , carbohydrate metabolism , denervation , metabolism , mean arterial pressure , obesity , glucose homeostasis , insulin resistance , heart rate
Clinical studies have shown that, in addition to lowering arterial pressure (AP), renal denervation (RDNx) improves glucose metabolism in drug‐resistant hypertensive obese patients. One‐fourth of these patients were females. We have observed a similar arterial pressure response in preliminary studies in obese genetically hypertensive male Schlager mice (BPH/2J). Although sex differences may exist regarding RDNx therapy, the effect of RDNx on AP and glucose metabolism in females specifically has not previously been studied. We hypothesized that, similar to males, RDNx will decrease AP and improve glucose metabolism in high fat fed female Schlager mice. 8‐week old mice were fed either a low fat diet (LFD; 10 KCal% from fat) or high fat diet (HFD; 45 KCal% from fat) for 10 weeks. Fasting blood glucose were measured on week 11 of the protocol. Radiotelemeters were implanted in the femoral artery on week 12 of the protocol for measurement of ambulatory AP. Body weight, food intake, body‐composition and glucose metabolism were measured throughout the study. After measuring baseline AP, LFD and HFD groups were then divided into RDNx or Sham treatment and followed for 14 days. After 10 weeks of diet, HFD versus LFD fed mice had increased body weight (30±1 vs. 26±1, g) and fasting blood glucose (83±3 vs. 68±4, mg/dL). HFD increased the baseline AP (124±4 mmHg) compared to LFD mice (112±4 mmHg). RDNx normalized AP in HFD mice (107±3) but had no effect on AP in LFD mice (106±4). Compared to sham treated mice, RDNx had no effect on fasting blood glucose or the glucose tolerance in LFD mice. In contrast to our hypothesis, fasting blood glucose was higher in RDNx‐HFD (76±3) compared to Sham‐HFD (69±4) mice. Similarly, the area under the curve for the glucose tolerance test was higher in RDNx‐HFD (555 ± 51) compared to Sham‐HFD (426 ± 24) mice. We conclude that RDNx effectively lowers AP in obese genetically hypertensive female Schlager mice, but also results in adverse effects on glucose metabolism. The mechanisms mediating these responses are currently underway and identifying these mechanisms could help develop targeted therapies for obese hypertensive females by clearly avoiding the adverse effects. Support or Funding Information NHLBI R01 HL116476