Altered ATP-sensitive potassium channels may underscore obesity-triggered increase in blood pressure<sup>1</sup>

Fan, Lihong; Tian, Hui; Ma, Aiqun; Zhi, Hu; Huo, Jianhua; Cao, Yunxia

doi:10.1111/j.1745-7254.2008.00810.x

Cited by 7 publications

(6 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Following the 20–24 week period of high‐fat diet intervention, body weight was significantly greater compared with controls, with body length, kidney and liver weight and retroperitoneal and gonadal fat mass being increased; retroperitoneal and gonadal fat mass were also significantly increased relative to body weight (Table 1). The fat content of this diet and of a 34% fat, cafeteria‐style diet have been shown to cause a significant increase in blood pressure and blood glucose (Fan et al 2008; Ng et al 2010; Rajia et al 2010). Arteries from both control and obese rats developed a graded myogenic constriction, although there was no significant difference in the level of vascular tone at 80 mmHg (control: 72.3 ± 5.7% D max , n = 30; obese: 72.6 ± 3.3% D max , n = 30; unpaired t test) or in the maximum vessel diameter ( D max ) recorded in 0 m m Ca 2+ PSS (control: 337 ± 10 μ m , n = 30; obese: 349.3 ± 8.3 μ m , n = 30).…”

Section: Resultsmentioning

confidence: 99%

Sympathetic overdrive in obesity involves purinergic hyperactivity in the resistance vasculature

Haddock

Hill

2011

The Journal of Physiology

View full text Add to dashboard Cite

Non-technical summary The maintenance of healthy blood pressure is influenced by the activity of the sympathetic perivascular nerves which surround small arteries and arterioles. Increases in sympathetic neurovascular control may play a role in the genesis and progression of cardiovascular disease during obesity. Our data show that sympathetic nerve-mediated vasoconstriction is augmented during diet-induced obesity and that ATP and purinergic mechanisms play a significant role. Changes occur due to an increase in sympathetic nerve density and release of ATP, with a potential contribution from a decreased sensitivity to sensory vasodilatory neurotransmitters. Improving control of sympathetic function through the identification of potential therapeutic targets is likely to lead to increased cardiovascular health benefits for overweight and obese individuals.Abstract While a close correlation exists in obese humans between sympathetic, adrenergic hyperactivity and structural and functional organ damage, a role for the co-transmitter, ATP, in vascular function remains unexplored. We therefore studied sympathetic nerve-mediated responses of pressurised small mesenteric arteries from control and obese rats. Diet-induced obesity significantly increased the amplitude of vasoconstriction to transmural nerve stimulation (1-10 Hz; P < 0.05). At 1 and 5 Hz, both adrenergic and purinergic responses were significantly augmented, while only the purinergic component was increased at 10 Hz (P < 0.05). Nerve stimulation at 1 Hz evoked contractions and underlying excitatory junction potentials (EJPs), which were both significantly increased in amplitude during obesity (P < 0.05) and abolished by αβ-methylene ATP (1 μM; desensitises purinergic receptors). The rise time and rate of decay of these EJPs were significant decreased (P < 0.05), without change in resting membrane potential. Amplitude and frequency of spontaneous EJPs and the density of perivascular sympathetic nerves were also significantly increased (P < 0.05). Inhibition of sensory neurotransmitter release (capsaicin; 10 μM) significantly increased the amplitude of nerve-mediated contraction (P < 0.05), with a greater effect in control than obese animals, although the density of sensory nerves was unaffected by obesity. We demonstrate that sympathetic nerve-mediated vasoconstriction is enhanced by diet-induced obesity due to upregulation of purinergic, in addition to adrenergic, neurotransmission. Changes result from increased perivascular sympathetic innervation and release of ATP. We conclude that augmented sympathetic control of vasoconstriction induced by obesity could contribute directly to hypertension and global organ damage. A decrease in sensitivity to sensory vasodilatory neurotransmitters may also affect these processes.

show abstract

Section: Resultsmentioning

confidence: 99%

Sympathetic overdrive in obesity involves purinergic hyperactivity in the resistance vasculature

Haddock

Hill

2011

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…The decreased insulin-reactivity, mediated by K ATP channels, in vessels from fructose-fed rats can be restored by block of endothelin-A receptors (1003), suggesting increased endothelial cell production of endothelin may contribute to the reduced K ATP channel function in this model. In diet-induced obesity in rats, relaxation of aortas and mesenteric arteries to a K ATP channel agonist, K ATP channel currents in SMCs and mRNA and protein expression from these two vessels were reduced (397, 399). Expression of SUR2B also is down regulated (398).…”

Section: Katp Channelsmentioning

confidence: 99%

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Tykocki

Boerman

Jackson

2017

Comprehensive Physiology

282

347

View full text Add to dashboard Cite

Vascular tone of resistance arteries and arterioles determines peripheral vascular resistance, contributing to the regulation of blood pressure and blood flow to, and within the body’s tissues and organs. Ion channels in the plasma membrane and endoplasmic reticulum of vascular smooth muscle cells (SMCs) in these blood vessels importantly contribute to the regulation of intracellular Ca2+ concentration, the primary determinant of SMC contractile activity and vascular tone. Ion channels provide the main source of activator Ca2+ that determines vascular tone, and strongly contribute to setting and regulating membrane potential, which, in turn, regulates the open-state-probability of voltage gated Ca2+ channels (VGCCs), the primary source of Ca2+ in resistance artery and arteriolar SMCs. Ion channel function is also modulated by vasoconstrictors and vasodilators, contributing to all aspects of the regulation of vascular tone. This review will focus on the physiology of VGCCs, voltage-gated K+ (KV) channels, large-conductance Ca2+-activated K+ (BKCa) channels, strong-inward-rectifier K+ (KIR) channels, ATP-sensitive K+ (KATP) channels, ryanodine receptors (RyRs), inositol 1,4,5-trisphosphate receptors (IP3Rs), and a variety of transient receptor potential (TRP) channels that contribute to pressure-induced myogenic tone in resistance arteries and arterioles, the modulation of the function of these ion channels by vasoconstrictors and vasodilators, their role in the functional regulation of tissue blood flow and their dysfunction in diseases such as hypertension, obesity, and diabetes.

show abstract

“…Additionally, functional studies have demonstrated that inhibition of the voltage-gated potassium channel Kv 1.3 has a strong anti-obesogenic effect in mice 27 28 29 . It has been suggested that alterations of potassium channels may also counteract obesity-triggered vascular dysfunction 30 31 .…”

Section: Discussionmentioning

confidence: 99%

An integrative study identifies KCNC2 as a novel predisposing factor for childhood obesity and the risk of diabetes in the Korean population

Hwang

Lee

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Obesity is a major risk factor for type 2 diabetes. To unravel the genetic determinants of obesity-associated diabetes, we performed a genome-wide study using the 1,000 Genomes-based imputation in a Korean childhood cohort (KoCAS-1, n = 484) and carried out de novo replication in an independent population (KoCAS-2, n = 1,548). A novel variant (rs10879834) with multiple diverse associations for obesity-related traits was also found to be replicated in an adult cohort (KARE, n = 8,842). Functional annotations using integrative epigenetic analyses identified biological significance and regulatory effects with an inverse methylation-expression correlation (cg27154343 in the 5′-UTR of the KCNC2 gene), tissue-specific enhancer mark (H3K4me1), and pathway enrichment (insulin signaling). Further functional studies in cellular and mouse models demonstrated that KCNC2 is associated with anti-obesogenic effects in the regulation of obesity-induced insulin resistance. KCNC2 shRNA transfection induced endoplasmic reticulum (ER) stress and hepatic gluconeogenesis. Overproduction of KCNC2 decreased ER stress, and treatment with metformin enhanced KCNC2 expression. Taken together, these data suggest that reduction of KCNC2 is associated with modified hepatic gluconeogenesis and increased ER stress on obesity-mediated diabetic risk. An integrative multi-omics analysis might reveal new functional and clinical implications related to the control of energy and metabolic homeostasis in humans.

show abstract

Altered ATP-sensitive potassium channels may underscore obesity-triggered increase in blood pressure¹

Cited by 7 publications

References 31 publications

Sympathetic overdrive in obesity involves purinergic hyperactivity in the resistance vasculature

Sympathetic overdrive in obesity involves purinergic hyperactivity in the resistance vasculature

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

An integrative study identifies KCNC2 as a novel predisposing factor for childhood obesity and the risk of diabetes in the Korean population

Contact Info

Product

Resources

About

Altered ATP-sensitive potassium channels may underscore obesity-triggered increase in blood pressure1

Cited by 7 publications

References 31 publications

Sympathetic overdrive in obesity involves purinergic hyperactivity in the resistance vasculature

Sympathetic overdrive in obesity involves purinergic hyperactivity in the resistance vasculature

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

An integrative study identifies KCNC2 as a novel predisposing factor for childhood obesity and the risk of diabetes in the Korean population

Contact Info

Product

Resources

About

Altered ATP-sensitive potassium channels may underscore obesity-triggered increase in blood pressure¹