Abstract
Obesity is a major risk factor for hypertension. The copresentation of hypertension and insulin resistance (IR) suggests a role for IR in blood pressure (BP) dysregulation. To test this hypothesis, peripheral IR has been genetically subtracted in a model of obesity by crossing leptin receptor mutant mice (KdbHPTP) with mice lacking protein tyrosine phosphatase 1B (insulin desensitizer, HdbKPTP) to generate obese insulin-sensitive mice (KdbKPTP). BP was recorded in lean (HdbHPTP, HdbKPTP) and obese (KdbHPTP, KdbKPTP) mice via telemetry, and a frequency analysis of the recording was performed to determine BP variability. Correction of IR in obese mice normalized BP values to baseline levels (HdbHPTP: 116±2 mm Hg; KdbHPTP: 129±4 mm Hg; KdbKPTP: 114±5 mm Hg) and restored BP variability by decreasing its standard deviation and the frequency of BP values over the upper autoregulatory limit of the kidneys. However, although IR-induced increases in proteinuria (versus 53±13 μg/d, HdbHPTP) were corrected in KdbKPTP (112±39 versus 422±159 μg/d, KdbHPTP), glomerular hypertrophy was not. IR reduced plasma aldosterone levels ruling out a role for mineralocorticoids in the development of hypertension. Taken together, these data indicate that correction of IR prevents hypertension, BP variability, and microalbuminuria in obese mice. Although the mechanism remains to be fully determined, increases in aldosterone or sympathoactivation of the cardiovascular system seem to be less likely contributors.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1273-1279 |
| Number of pages | 7 |
| Journal | Hypertension |
| Volume | 60 |
| Issue number | 5 |
| DOIs | |
| State | Published - Nov 1 2012 |
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Keywords
- aldosterone
- db/db mice
- obese mice
- pressure variability
ASJC Scopus subject areas
- Internal Medicine
Cite this
Increasing peripheral insulin sensitivity by protein tyrosine phosphatase 1B deletion improves control of blood pressure in obesity. / De Chantemèle, Eric J.Belin; Ali, Mohammed Irfan; Mintz, James D.; Rainey, William E.; Tremblay, Michel L.; Fulton, David J.; Stepp, David W.
In: Hypertension, Vol. 60, No. 5, 01.11.2012, p. 1273-1279.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Increasing peripheral insulin sensitivity by protein tyrosine phosphatase 1B deletion improves control of blood pressure in obesity
AU - De Chantemèle, Eric J.Belin
AU - Ali, Mohammed Irfan
AU - Mintz, James D.
AU - Rainey, William E.
AU - Tremblay, Michel L.
AU - Fulton, David J.
AU - Stepp, David W.
PY - 2012/11/1
Y1 - 2012/11/1
N2 - Obesity is a major risk factor for hypertension. The copresentation of hypertension and insulin resistance (IR) suggests a role for IR in blood pressure (BP) dysregulation. To test this hypothesis, peripheral IR has been genetically subtracted in a model of obesity by crossing leptin receptor mutant mice (KdbHPTP) with mice lacking protein tyrosine phosphatase 1B (insulin desensitizer, HdbKPTP) to generate obese insulin-sensitive mice (KdbKPTP). BP was recorded in lean (HdbHPTP, HdbKPTP) and obese (KdbHPTP, KdbKPTP) mice via telemetry, and a frequency analysis of the recording was performed to determine BP variability. Correction of IR in obese mice normalized BP values to baseline levels (HdbHPTP: 116±2 mm Hg; KdbHPTP: 129±4 mm Hg; KdbKPTP: 114±5 mm Hg) and restored BP variability by decreasing its standard deviation and the frequency of BP values over the upper autoregulatory limit of the kidneys. However, although IR-induced increases in proteinuria (versus 53±13 μg/d, HdbHPTP) were corrected in KdbKPTP (112±39 versus 422±159 μg/d, KdbHPTP), glomerular hypertrophy was not. IR reduced plasma aldosterone levels ruling out a role for mineralocorticoids in the development of hypertension. Taken together, these data indicate that correction of IR prevents hypertension, BP variability, and microalbuminuria in obese mice. Although the mechanism remains to be fully determined, increases in aldosterone or sympathoactivation of the cardiovascular system seem to be less likely contributors.
AB - Obesity is a major risk factor for hypertension. The copresentation of hypertension and insulin resistance (IR) suggests a role for IR in blood pressure (BP) dysregulation. To test this hypothesis, peripheral IR has been genetically subtracted in a model of obesity by crossing leptin receptor mutant mice (KdbHPTP) with mice lacking protein tyrosine phosphatase 1B (insulin desensitizer, HdbKPTP) to generate obese insulin-sensitive mice (KdbKPTP). BP was recorded in lean (HdbHPTP, HdbKPTP) and obese (KdbHPTP, KdbKPTP) mice via telemetry, and a frequency analysis of the recording was performed to determine BP variability. Correction of IR in obese mice normalized BP values to baseline levels (HdbHPTP: 116±2 mm Hg; KdbHPTP: 129±4 mm Hg; KdbKPTP: 114±5 mm Hg) and restored BP variability by decreasing its standard deviation and the frequency of BP values over the upper autoregulatory limit of the kidneys. However, although IR-induced increases in proteinuria (versus 53±13 μg/d, HdbHPTP) were corrected in KdbKPTP (112±39 versus 422±159 μg/d, KdbHPTP), glomerular hypertrophy was not. IR reduced plasma aldosterone levels ruling out a role for mineralocorticoids in the development of hypertension. Taken together, these data indicate that correction of IR prevents hypertension, BP variability, and microalbuminuria in obese mice. Although the mechanism remains to be fully determined, increases in aldosterone or sympathoactivation of the cardiovascular system seem to be less likely contributors.
KW - aldosterone
KW - db/db mice
KW - obese mice
KW - pressure variability
UR - http://www.scopus.com/inward/record.url?scp=84868207626&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84868207626&partnerID=8YFLogxK
U2 - 10.1161/HYPERTENSIONAHA.112.196295
DO - 10.1161/HYPERTENSIONAHA.112.196295
M3 - Article
C2 - 23045458
AN - SCOPUS:84868207626
VL - 60
SP - 1273
EP - 1279
JO - Hypertension
JF - Hypertension
SN - 0194-911X
IS - 5
ER -