Abstract
Abdominal obesity and/or a high intake of fructose may cause hypertension. K+ channels, Na/K-ATPase, and voltage-gated Ca2+ channels are crucial determinants of resistance artery tone and thus the control of blood pressure. Limited information is available on the role of K+ transporters in long-term diet-induced hypertension in rats. We hypothesized that a 28-week diet rich in fat, fructose, or both, will lead to changes in K+ transporter expression and function, which is associated with increased blood pressure and decreased arterial function. Male Sprague–Dawley (SD) rats received a diet containing normal chow (Control), high-fat chow (High Fat), high-fructose in drinking water (High Fructose), or a combination of high-fat and high-fructose diet (High Fat/Fruc) for 28 weeks from the age of 4 weeks. Measurements included body weight (BW), systolic blood pressure (SBP), mRNA expression of vascular K+ transporters, and vessel myography in small mesenteric arteries (SMAs). BW was increased in the High Fat and High Fat/Fruc groups, and SBP was increased in the High Fat/Fruc group. mRNA expression of small conductance calcium-activated K+ channel (SKCa), intermediate conductance calcium-activated K+ (IKCa), and Kir2.1 inward rectifier K+ channels were reduced in the High Fat/Fruc group. Reduced endothelium-derived hyperpolarization (EDH)-type relaxation to acetylcholine (ACh) was seen in the High Fat and High Fat/Fruc groups. Ba2+-sensitive dilatation to extracellular K+ was impaired in all the experimental diet groups. In conclusion, reduced expression and function of SKCa, IKCa, and Kir2.1 channels are associated with elevated blood pressure in rats fed a long-term High Fat/Fruc. Rats fed a 28-week High Fat/Fruc provide a relevant model of diet-induced hypertension.
- hypertension
- diet-induced obesity
- potassium channels
- small arteries
- vascular tone
Abbreviations
- ACh,
- acetylcholine;
- ActB,
- β-actin reference gene;
- AUC,
- area under curve;
- BKCa,
- big conductance calcium-activated K+ channel;
- BW,
- body weight;
- EC,
- endothelial cell;
- EC50,
- half-maximal effective concentration;
- EDH,
- endothelium-derived hyperpolarization;
- FMVD,
- flow-mediated vasodilatation;
- IKCa,
- intermediate conductance calcium-activated K+ channel;
- Kir2.1,
- inward rectifier K+ channel subtype 2.1;
- L-NAME,
- Nω-Nitro-L-arginine methyl ester hydrochloride;
- MAP,
- mean arterial blood pressure;
- NE,
- norepinephrine;
- NO,
- nitric oxide;
- PE,
- phenylephrine;
- PSS,
- physiological saline solution;
- PGI2,
- prostacyclin;
- Q-PCR,
- quantitative real-time PCR;
- SBP,
- systolic blood pressure;
- SD,
- Sprague–Dawley;
- SKCa,
- small conductance calcium-activated K+ channel;
- SMA,
- small mesenteric artery;
- TPR,
- total peripheral resistance;
- VSMC,
- vascular smooth muscle cell
- © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society