Long-term diet-induced hypertension in rats is associated with reduced expression and function of small artery SK_Ca, IK_Ca, and Kir2.1 channels

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 (SK_Ca), intermediate conductance calcium-activated K⁺ (IK_Ca), 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 SK_Ca, IK_Ca, 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.