BK channel ß1-subunit deficiency exacerbates vascular fibrosis and remodelling but does not promote hypertension in high-fat fed obesity in mice.
J Hypertens
; 33(8): 1611-23, 2015 Aug.
Article
in En
| MEDLINE
| ID: mdl-26049174
ABSTRACT
OBJECTIVE:
Reduced expression or increased degradation of BK (large conductance Ca-activated K) channel ß1-subunits has been associated with increased vascular tone and hypertension in some metabolic diseases. The contribution of BK channel function to control of blood pressure (BP), heart rate (HR) and vascular function/structure was determined in wild-type and BK channel ß1-subunit knockout mice fed a high-fat or control diet. METHODS ANDRESULTS:
After 24 weeks of high-fat diet, wild-type and BK ß1-knockout mice were obese, diabetic, but normotensive. High-fat-BK ß1-knockout mice had decreased HR, while high-fat-wild-type mice had increased HR compared with mice on the control diet. Ganglion blockade caused a greater fall in BP and HR in mice on a high-fat diet than in mice on the control diet. ß1-adrenergic receptor blockade reduced BP and HR equally in all groups. α1-adrenergic receptor blockade decreased BP in high-fat-BK ß1-knockout mice only. Echocardiographic evaluation revealed left ventricular hypertrophy in high-fat-BK ß1-knockout mice. Although under anaesthesia, mice on a high-fat diet had higher absolute stroke volume and cardiac output, these measures were similar to control mice when adjusted for body weight. Mesenteric arteries from high-fat-BK ß1-knockout mice had higher norepinephrine reactivity, greater wall thickness and collagen accumulation than high-fat-wild-type mesenteric arteries. Compared with control-wild-type mesenteric arteries, high-fat-wild-type mesenteric arteries had blunted contractile responses to a BK channel blocker, although BK α-subunit (protein) and ß1-subunit (mRNA) expression were unchanged.CONCLUSION:
BK channel deficiency promotes increased sympathetic control of BP, and vascular dysfunction, remodelling and fibrosis, but does not cause hypertension in high-fat fed mice.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Large-Conductance Calcium-Activated Potassium Channel beta Subunits
/
Mesenteric Arteries
/
Obesity
Type of study:
Diagnostic_studies
/
Etiology_studies
Limits:
Animals
Language:
En
Journal:
J Hypertens
Year:
2015
Document type:
Article
Affiliation country:
United States