Sodium channels are required during in vivo sodium chloride hyperosmolarity to stimulate increase in intestinal endothelial nitric oxide production

Zani, Brett G.; Bohlen, H. G.

doi:10.1152/ajpheart.00644.2004

Cited by 31 publications

(36 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NO is a key mediator of tissue perfusion in the mesenteric circulation, in both the response to flow (2) and the absorption of nutrients (1,17,25). The effect of vascular risk factors on NO-mediated dilation has been the subject of intensive study, and recent evidence has documented that obesity also impairs NO-dependent dilation in both clinical (6, 21) and experimental animal populations (3, 5, 24).…”

Section: Discussionmentioning

confidence: 99%

Reduced constrictor reactivity balances impaired vasodilation in the mesenteric circulation of the obese Zucker rat

Romanko¹,

Stepp²

2005

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Romanko, Olga P., and David W. Stepp. Reduced constrictor reactivity balances impaired vasodilation in the mesenteric circulation of the obese Zucker rat. Am J Physiol Heart Circ Physiol 289: H2097-H2102, 2005. First published June 10, 2005; doi:10.1152/ajpheart.00213.2005.-Obesity causes whole body insulin resistance and impaired vasodilation to nitric oxide (NO). Because NO is a major contributor to the regulation of mesenteric blood flow, the mesenteric circulation of obese animals is faced with reduced capacity to increase flow and increased demand for flow associated with elevated consumption of food. This study hypothesized that insulin resistance impairs NO-mediated dilation but that constrictor reactivity would be reduced to compensate in obese animals. We further hypothesized that elevated superoxide levels caused impaired responses to NO in insulin resistance. Vasodilator reactivity and vasoconstrictor reactivity of mesenteric resistance arteries from lean (LZR) and obese (OZR) Zucker rats were examined in vitro using videomicroscopy. Insulin resistance independent of obesity was induced via fructose feeding in LZR (FF-LZR). Endothelium-dependent NO-mediated dilation was reduced in OZR and FF-LZR compared with LZR. Impairments in NO-mediated dilation were reversed with 1 mM tempol, a SOD mimetic. Constrictor reactivity to norepinephrine was reduced in OZR but not in FF-LZR relative to LZR. Basal mesenteric vascular resistance was similar in LZR and OZR despite impaired NO-dependent dilation in OZR. Mesenteric vascular resistance was increased in FF-LZR relative to LZR. These data indicate that there is reduced constrictor reactivity in OZR that may offset the impaired NO-mediated dilation and preserve mesenteric blood flow in hyperphagic, obese animals. microcirculation; adrenergic; nitric oxide; superoxide OBESITY IS AN EMERGING EPIDEMIC in Western cultures, especially in the United States, where an estimated 180 million people are overweight. The causes of obesity vary but include metabolic impairment, a high-fat diet, and overeating (hyperphagia). Functional hyperemia of the gut is required for food absorption and thus weight gain, but the effects of obesity and chronic hyperphagia on mesenteric perfusion are incompletely understood.Obesity also induces whole body insulin resistance, resulting in impaired control of plasma glucose, hyperinsulinemia, and chronic triglyceride dyslipidemia. Insulin resistance is considered an emerging risk factor for vascular disease and has been documented to impair nitric oxide (NO)-dependent mesenteric vasodilation in animal models of insulin resistance (20,(22)(23)(24). Given that NO is a major contributor to absorptive functional hyperemia (1, 9, 12, 17) and flow-mediated regulation (2,12,19), it raises the question of how the mesenteric circulation compensates for the impaired dilator response caused by insulin resistance against the elevated metabolic demands associated with increased ingestion of food in obese or hyperphagic individuals. Potential mechanisms in...

show abstract

Section: Discussionmentioning

confidence: 99%

Reduced constrictor reactivity balances impaired vasodilation in the mesenteric circulation of the obese Zucker rat

Romanko¹,

Stepp²

2005

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…Many cells of all organs use bumetanide sensitive Na + -K + -2Cl − cotransport to quickly respond to changes in environmental osmolarity [29][30][31]. The same location on a given tubule was followed throughout the experiment.…”

Section: Elevated Nacl Concentration Vs Mannitolmentioning

confidence: 99%

“…When in vivo arterioles of the small intestine were exposed to hypertonic 320-380 mOsm NaCl, such as that associated with villus nutrient absorption [1], there was an immediate and sustained increase in nitric oxide concentration, [NO] [2;3]. Equivalent mannitol hyperosmolarity caused both much smaller increases in intestinal perivascular [NO] and arteriolar dilation [2][3][4]. In the intestinal endothelial cells, sodium ions predominantly enter the endothelial cells through Na + /K + / 2Cl + cotransport because bumetanide suppressed both increased [NO] and vasodilation [3].…”

Section: Introductionmentioning

confidence: 99%

“…Equivalent mannitol hyperosmolarity caused both much smaller increases in intestinal perivascular [NO] and arteriolar dilation [2][3][4]. In the intestinal endothelial cells, sodium ions predominantly enter the endothelial cells through Na + /K + / 2Cl + cotransport because bumetanide suppressed both increased [NO] and vasodilation [3].…”

Section: Introductionmentioning

confidence: 99%

“…Once sodium is within the cells, the Na + /Ca +2 transporter must be active for increased [NO] to develop and cause the subsequent increase in [NO] and simultaneous vasodilation [3]. A similar set of mechanisms may exist in renal tubules because they have endothelial and neuronal nitric oxide synthase enzymes (eNOS, nNOS) [5;6], a variety of sodium uptake mechanisms, including the Na + /K + /2Cl − cotransporter [7] and Na + /H + cotransporters [8;9], and absorb a great deal of NaCl from both isotonic and hypertonic lumen solutions.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Nitric oxide production by mouse renal tubules can be increased by a sodium-dependent mechanism

et al. 2007

View full text Add to dashboard Cite

Renal tubules process large amounts of NaCl that other investigators indicate increases tubular generation of nitric oxide. We questioned whether medullary or superficial cortical tubules would have the greater increase in nitric oxide concentration, [NO], when stressed by sodium and if the sodium/calcium exchanger was involved. Sodium stress in proximal tubules is due to the large amount of sodium absorbed and medullary tubules exist in a hypertonic sodium environment. To sodium stress the tissue, mouse kidney slices were exposed to monensin to allow passive entry of sodium ions from isotonic media and in separate studies, 400 and 600 mOsm NaCl was used. [NO] was measured with microelectrodes. Monensin (10 μM) caused a sustained increase in medullary and cortical [NO] to ∼180% of control and 400 mOsm NaCl caused a similar initial increase in [NO] that then subsided. 600 mOsm NaCl caused a more sustained increase in [NO] of >250% of control. L-NAME strongly attenuated the increased [NO] during sodium stress. The increase in [NO] during NaCl elevation was due to sodium ions because mannitol hyperosmolarity caused ∼20% of the increase in [NO]. Entry of sodium during NaCl hyperosmolarity was through bumetanide sensitive channels because the drug suppressed increased [NO]. Blockade of the sodium/calcium ion exchanger strongly suppressed the increased [NO] during monensin, to increase sodium entry into cells, and the elevated NaCl concentration. The data support a sodium -NO linkage that increased NO signaling in proportion to sodium stress by cortical tubules and was highly dependent upon sodium-calcium exchange.

show abstract

Gastrointestinal Blood Flow

Vowinkel

Granger

2015

Yamada' S Textbook of Gastroenterology

View full text Add to dashboard Cite

Sodium channels are required during in vivo sodium chloride hyperosmolarity to stimulate increase in intestinal endothelial nitric oxide production

Abstract: . Sodium channels are required during in vivo sodium chloride hyperosmolarity to stimulate increase in intestinal endothelial nitric oxide production.

Cited by 31 publications

References 41 publications

Reduced constrictor reactivity balances impaired vasodilation in the mesenteric circulation of the obese Zucker rat

Reduced constrictor reactivity balances impaired vasodilation in the mesenteric circulation of the obese Zucker rat

Nitric oxide production by mouse renal tubules can be increased by a sodium-dependent mechanism

Gastrointestinal Blood Flow

Contact Info

Product

Resources

About