Long-term excess fat and/or fructose ingestion causes changes in small artery K+ transporter expression and function with effects on blood pressure

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Long-term excess fat and/or fructose ingestion causes changes in small artery K+ transporter expression and function with effects on blood pressure. / Olsen, A. K.; Salomonsson, M.; Sørensen, C. M.; Holstein-Rathlou, N-H.; Jensen, L. J.

2016. Abstract fra Pharmacological aspects of microvascular cell-cell signaling and CVS disease, Oxford, Storbritannien.

Publikation: KonferencebidragKonferenceabstrakt til konferenceForskningfagfællebedømt

Harvard

Olsen, AK, Salomonsson, M, Sørensen, CM, Holstein-Rathlou, N-H & Jensen, LJ 2016, 'Long-term excess fat and/or fructose ingestion causes changes in small artery K+ transporter expression and function with effects on blood pressure', Pharmacological aspects of microvascular cell-cell signaling and CVS disease, Oxford, Storbritannien, 21/09/2016 - 22/09/2016.

APA

Olsen, A. K., Salomonsson, M., Sørensen, C. M., Holstein-Rathlou, N-H., & Jensen, L. J. (2016). Long-term excess fat and/or fructose ingestion causes changes in small artery K+ transporter expression and function with effects on blood pressure. Abstract fra Pharmacological aspects of microvascular cell-cell signaling and CVS disease, Oxford, Storbritannien.

Vancouver

Olsen AK, Salomonsson M, Sørensen CM, Holstein-Rathlou N-H, Jensen LJ. Long-term excess fat and/or fructose ingestion causes changes in small artery K+ transporter expression and function with effects on blood pressure. 2016. Abstract fra Pharmacological aspects of microvascular cell-cell signaling and CVS disease, Oxford, Storbritannien.

Author

Olsen, A. K. ; Salomonsson, M. ; Sørensen, C. M. ; Holstein-Rathlou, N-H. ; Jensen, L. J. / Long-term excess fat and/or fructose ingestion causes changes in small artery K+ transporter expression and function with effects on blood pressure. Abstract fra Pharmacological aspects of microvascular cell-cell signaling and CVS disease, Oxford, Storbritannien.1 s.

Bibtex

@conference{66df9da962b64675bbfa9783f5476402,
title = "Long-term excess fat and/or fructose ingestion causes changes in small artery K+ transporter expression and function with effects on blood pressure",
abstract = "INTRODUCTION: Excess visceral fat may lead to serious disease such as hypertension, type-2 diabetes, myocardial infarcts and stroke. Obesity is recognized as a world-wide problem reaching epidemic propor-tions. Genetic rodent models of obesity and hypertension may not reflect the same pathophysiological mechanisms as rodents fed a high-calorie diet for > 10 weeks. The precise role of fat vs. sugar or its combination in cardiovascular diseases must be elucidated using more realistic models. K+ is the most important ion for controlling the membrane potential in vascular smooth muscle and thus K+ channels, Na/K-ATPase, and voltage-gated Ca2+ channels are crucial determinants of resistance artery tone. Only scarce information is available on the role of K+ transporters in pathophysiological mechanisms induced by long-term feeding of laboratory rats with either high-fat, high-fructose or high-fat/high-fructose diet. HYPOTHESIS: A 28-week diet consisting of high-fat or high-fructose, or both, will lead to changes in K+ transporter expression and function, which will be linked with changes in blood pressure, arterial smooth muscle function, endothelial function and passive structural/mechanical properties. METHODS: Male Sprague Dawley rats (4 weeks) were randomized into 4 diet groups receiving a diet with normal chow (CTR, N=19), high-fat chow (60{\%} saturated fat, FAT, N=18), high-fructose (10{\%} in drinking water; FRUC, N=15), or a combination of fat/fructose (FAT/FRUC, N=15) for 28 weeks. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography once weekly. Gene expression in small mesenteric arteries (2nd-3rd order SMA) was measured at the end of study using real-time quantitative PCR (q-PCR). Arterial function and passive structure, mechanical properties were measured by pressure and wire myography. Pharmacological modulators of K+ transporters were used to assess their potential role. RESULTS: Body weight was significantly (P<0.05) increased in the FAT and FAT/FRUC groups vs. CTR. SBP measured from 11-28 weeks of age was significantly increased in FRUC and FAT/FRUC vs. CTR (P<0.05). A comparison of mRNA expression of KATP, Kir, KV1.2, KV1.5, KV7.4, SKCa, IKCa, BKCa, Na/K-1, Na/K-2, and CaV1.2 transporters in the 4 diet groups revealed an up-regulation of Kir and KV7.4 channels in FAT vs. CTR, and a down-regulation of SKCa and IKCa channels in FAT/FRUC vs. CTR (P<0.05). Testing of endothelial function with pressure myography showed no difference between diet groups for flow-mediated vasodilatation or SK/IK channel activation using NS309 (1 µM). Wire myography showed a reduced EDH-type relaxation to increasing ACh concentrations in the presence of L-Name (100 µM) and Indomethacin (10 µM) in the FAT/FRUC group vs. CTR (P<0.05), consistent with reduced SK/IK channel expression. Pressure myography showed no diet-induced differences in constrictions to high-KCl (75 mM), increasing phenylephrine (PE) concentrations, or the KV7 channel blocker XE-991 (10 µM). XE-991 reduced the Log(EC50) of PE to a similar extent in all diet groups. XE-991 significantly increased vasomotion amplitude and reduced vasomotion frequency measured at a half-maximal [PE] in FRUC vs. CTR (P<0.05). Dilatation to excess bath [KCl] was significantly impaired in the FAT (at 9.5 mM KCl, P<0.05), FRUC (P<0.05), and FAT/FRUC groups (both at 12 mM KCl, P<0.01) vs. CTR. In age-matched lean control rats (N=7) BaCl2 (50 µM) and BaCl2 + Ouabain (100 µM) (but not Ouabain alone), significantly inhibited the excess KCl dilatations (P<0.05). There were no major effects of the different diets concerning structural remodelling or arterial stiffness. CONCLUSION: Our data indicates that transcriptional and/or functional changes in SK/IK and Kir channels may lead to discrete functional changes in small arteries that may cause hypertension in rats fed a long-term high-fructose or a high-fat/high-fructose diet. A high-fat diet may lead to compensatory changes that prevent an increase in SBP.",
author = "Olsen, {A. K.} and M. Salomonsson and S{\o}rensen, {C. M.} and N-H. Holstein-Rathlou and Jensen, {L. J.}",
note = "C16.27 ; Pharmacological aspects of microvascular cell-cell signaling and CVS disease ; Conference date: 21-09-2016 Through 22-09-2016",
year = "2016",
month = "9",
day = "22",
language = "English",

}

RIS

TY - ABST

T1 - Long-term excess fat and/or fructose ingestion causes changes in small artery K+ transporter expression and function with effects on blood pressure

AU - Olsen, A. K.

AU - Salomonsson, M.

AU - Sørensen, C. M.

AU - Holstein-Rathlou, N-H.

AU - Jensen, L. J.

N1 - C16.27

PY - 2016/9/22

Y1 - 2016/9/22

N2 - INTRODUCTION: Excess visceral fat may lead to serious disease such as hypertension, type-2 diabetes, myocardial infarcts and stroke. Obesity is recognized as a world-wide problem reaching epidemic propor-tions. Genetic rodent models of obesity and hypertension may not reflect the same pathophysiological mechanisms as rodents fed a high-calorie diet for > 10 weeks. The precise role of fat vs. sugar or its combination in cardiovascular diseases must be elucidated using more realistic models. K+ is the most important ion for controlling the membrane potential in vascular smooth muscle and thus K+ channels, Na/K-ATPase, and voltage-gated Ca2+ channels are crucial determinants of resistance artery tone. Only scarce information is available on the role of K+ transporters in pathophysiological mechanisms induced by long-term feeding of laboratory rats with either high-fat, high-fructose or high-fat/high-fructose diet. HYPOTHESIS: A 28-week diet consisting of high-fat or high-fructose, or both, will lead to changes in K+ transporter expression and function, which will be linked with changes in blood pressure, arterial smooth muscle function, endothelial function and passive structural/mechanical properties. METHODS: Male Sprague Dawley rats (4 weeks) were randomized into 4 diet groups receiving a diet with normal chow (CTR, N=19), high-fat chow (60% saturated fat, FAT, N=18), high-fructose (10% in drinking water; FRUC, N=15), or a combination of fat/fructose (FAT/FRUC, N=15) for 28 weeks. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography once weekly. Gene expression in small mesenteric arteries (2nd-3rd order SMA) was measured at the end of study using real-time quantitative PCR (q-PCR). Arterial function and passive structure, mechanical properties were measured by pressure and wire myography. Pharmacological modulators of K+ transporters were used to assess their potential role. RESULTS: Body weight was significantly (P<0.05) increased in the FAT and FAT/FRUC groups vs. CTR. SBP measured from 11-28 weeks of age was significantly increased in FRUC and FAT/FRUC vs. CTR (P<0.05). A comparison of mRNA expression of KATP, Kir, KV1.2, KV1.5, KV7.4, SKCa, IKCa, BKCa, Na/K-1, Na/K-2, and CaV1.2 transporters in the 4 diet groups revealed an up-regulation of Kir and KV7.4 channels in FAT vs. CTR, and a down-regulation of SKCa and IKCa channels in FAT/FRUC vs. CTR (P<0.05). Testing of endothelial function with pressure myography showed no difference between diet groups for flow-mediated vasodilatation or SK/IK channel activation using NS309 (1 µM). Wire myography showed a reduced EDH-type relaxation to increasing ACh concentrations in the presence of L-Name (100 µM) and Indomethacin (10 µM) in the FAT/FRUC group vs. CTR (P<0.05), consistent with reduced SK/IK channel expression. Pressure myography showed no diet-induced differences in constrictions to high-KCl (75 mM), increasing phenylephrine (PE) concentrations, or the KV7 channel blocker XE-991 (10 µM). XE-991 reduced the Log(EC50) of PE to a similar extent in all diet groups. XE-991 significantly increased vasomotion amplitude and reduced vasomotion frequency measured at a half-maximal [PE] in FRUC vs. CTR (P<0.05). Dilatation to excess bath [KCl] was significantly impaired in the FAT (at 9.5 mM KCl, P<0.05), FRUC (P<0.05), and FAT/FRUC groups (both at 12 mM KCl, P<0.01) vs. CTR. In age-matched lean control rats (N=7) BaCl2 (50 µM) and BaCl2 + Ouabain (100 µM) (but not Ouabain alone), significantly inhibited the excess KCl dilatations (P<0.05). There were no major effects of the different diets concerning structural remodelling or arterial stiffness. CONCLUSION: Our data indicates that transcriptional and/or functional changes in SK/IK and Kir channels may lead to discrete functional changes in small arteries that may cause hypertension in rats fed a long-term high-fructose or a high-fat/high-fructose diet. A high-fat diet may lead to compensatory changes that prevent an increase in SBP.

AB - INTRODUCTION: Excess visceral fat may lead to serious disease such as hypertension, type-2 diabetes, myocardial infarcts and stroke. Obesity is recognized as a world-wide problem reaching epidemic propor-tions. Genetic rodent models of obesity and hypertension may not reflect the same pathophysiological mechanisms as rodents fed a high-calorie diet for > 10 weeks. The precise role of fat vs. sugar or its combination in cardiovascular diseases must be elucidated using more realistic models. K+ is the most important ion for controlling the membrane potential in vascular smooth muscle and thus K+ channels, Na/K-ATPase, and voltage-gated Ca2+ channels are crucial determinants of resistance artery tone. Only scarce information is available on the role of K+ transporters in pathophysiological mechanisms induced by long-term feeding of laboratory rats with either high-fat, high-fructose or high-fat/high-fructose diet. HYPOTHESIS: A 28-week diet consisting of high-fat or high-fructose, or both, will lead to changes in K+ transporter expression and function, which will be linked with changes in blood pressure, arterial smooth muscle function, endothelial function and passive structural/mechanical properties. METHODS: Male Sprague Dawley rats (4 weeks) were randomized into 4 diet groups receiving a diet with normal chow (CTR, N=19), high-fat chow (60% saturated fat, FAT, N=18), high-fructose (10% in drinking water; FRUC, N=15), or a combination of fat/fructose (FAT/FRUC, N=15) for 28 weeks. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography once weekly. Gene expression in small mesenteric arteries (2nd-3rd order SMA) was measured at the end of study using real-time quantitative PCR (q-PCR). Arterial function and passive structure, mechanical properties were measured by pressure and wire myography. Pharmacological modulators of K+ transporters were used to assess their potential role. RESULTS: Body weight was significantly (P<0.05) increased in the FAT and FAT/FRUC groups vs. CTR. SBP measured from 11-28 weeks of age was significantly increased in FRUC and FAT/FRUC vs. CTR (P<0.05). A comparison of mRNA expression of KATP, Kir, KV1.2, KV1.5, KV7.4, SKCa, IKCa, BKCa, Na/K-1, Na/K-2, and CaV1.2 transporters in the 4 diet groups revealed an up-regulation of Kir and KV7.4 channels in FAT vs. CTR, and a down-regulation of SKCa and IKCa channels in FAT/FRUC vs. CTR (P<0.05). Testing of endothelial function with pressure myography showed no difference between diet groups for flow-mediated vasodilatation or SK/IK channel activation using NS309 (1 µM). Wire myography showed a reduced EDH-type relaxation to increasing ACh concentrations in the presence of L-Name (100 µM) and Indomethacin (10 µM) in the FAT/FRUC group vs. CTR (P<0.05), consistent with reduced SK/IK channel expression. Pressure myography showed no diet-induced differences in constrictions to high-KCl (75 mM), increasing phenylephrine (PE) concentrations, or the KV7 channel blocker XE-991 (10 µM). XE-991 reduced the Log(EC50) of PE to a similar extent in all diet groups. XE-991 significantly increased vasomotion amplitude and reduced vasomotion frequency measured at a half-maximal [PE] in FRUC vs. CTR (P<0.05). Dilatation to excess bath [KCl] was significantly impaired in the FAT (at 9.5 mM KCl, P<0.05), FRUC (P<0.05), and FAT/FRUC groups (both at 12 mM KCl, P<0.01) vs. CTR. In age-matched lean control rats (N=7) BaCl2 (50 µM) and BaCl2 + Ouabain (100 µM) (but not Ouabain alone), significantly inhibited the excess KCl dilatations (P<0.05). There were no major effects of the different diets concerning structural remodelling or arterial stiffness. CONCLUSION: Our data indicates that transcriptional and/or functional changes in SK/IK and Kir channels may lead to discrete functional changes in small arteries that may cause hypertension in rats fed a long-term high-fructose or a high-fat/high-fructose diet. A high-fat diet may lead to compensatory changes that prevent an increase in SBP.

UR - https://www.bps.ac.uk/cvs#Overview

M3 - Conference abstract for conference

T2 - Pharmacological aspects of microvascular cell-cell signaling and CVS disease

Y2 - 21 September 2016 through 22 September 2016

ER -

ID: 171121963