TY - JOUR

T1 - Long-term diet-induced hypertension in rats is associated with reduced expression and function of small artery SKCa, IKCa, and Kir2.1 channels

AU - Gradel, Anna Katrina Jógvansdóttir

AU - Salomonsson, Max

AU - Sørensen, Charlotte Mehlin

AU - von Holstein-Rathlou, Niels-Henrik

AU - Jensen, Lars Jørn

N1 - Clinical perspectives • We investigated whether a long-term (28 weeks) diet rich in fat, fructose, or both fat and fructose would lead to changes in K+ transporter expression, and whether this was associated with increased blood pressure and decreased arterial function. • In the present study, we detected a reduced mRNA expression of SKCa, IKCa, and Kir2.1 K+ channels in rats fed a diet with High Fat and High Fructose, and this was associated with increased SBP, reduced EDH-type relaxation, and reduced K+-induced dilatation in small arteries. • Our data point to a role of SKCa, IKCa, and Kir2.1 K+ channels in diet-induced hypertension, and indicate that rats fed a long-term diet consisting of High Fat and Fructose may be a valuable model for studying hypertension induced by the diet.

PY - 2018/2/28

Y1 - 2018/2/28

N2 - Rationale: 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.Hypothesis: 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.Methods and Results: Male Sprague Dawley 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 age 4-weeks. Measurements included body weight (BW), systolic blood pressure (SBP), mRNA expression of vascular K+ transporters, and vessel myography in small mesenteric arteries. 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 SKCa, IKCa, and Kir2.1 K+ channels were reduced in the High Fat/Fruc group. Reduced EDH-type relaxation to acetylcholine was seen in the High Fat and High Fat/Fruc groups. Ba2+-sensitive dilatation to extracellular K+ was impaired in all experimental diet groups.Conclusions: Reduced expression and function of SKCa, IKCa and Kir2.1 channels is associated with elevated blood pressure in rats fed a long-term high fat/high fructose diet. Rats fed a 28-week high fat/high fructose diet provide a relevant model of diet-induced hypertension.

AB - Rationale: 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.Hypothesis: 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.Methods and Results: Male Sprague Dawley 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 age 4-weeks. Measurements included body weight (BW), systolic blood pressure (SBP), mRNA expression of vascular K+ transporters, and vessel myography in small mesenteric arteries. 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 SKCa, IKCa, and Kir2.1 K+ channels were reduced in the High Fat/Fruc group. Reduced EDH-type relaxation to acetylcholine was seen in the High Fat and High Fat/Fruc groups. Ba2+-sensitive dilatation to extracellular K+ was impaired in all experimental diet groups.Conclusions: Reduced expression and function of SKCa, IKCa and Kir2.1 channels is associated with elevated blood pressure in rats fed a long-term high fat/high fructose diet. Rats fed a 28-week high fat/high fructose diet provide a relevant model of diet-induced hypertension.

U2 - 10.1042/CS20171408

DO - 10.1042/CS20171408

M3 - Journal article

VL - 132

SP - 461

EP - 474

JO - Clinical Science

JF - Clinical Science

SN - 0143-5221

IS - 4

ER -