Direct in vivo measurement of flow-dependent nitric oxide production in mesenteric resistance arteries

Hyre, Charles E.; Unthank, Joseph L.; Dalsing, Michael C.

doi:10.1016/s0741-5214(98)70239-3

Cited by 16 publications

(12 citation statements)

References 34 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3). This observation is consistent with earlier in vivo findings in healthy animals (6,31) and with the suppression of flow-mediated NO production observed by Bohlen in obese rats (6). The impairment of SHR flowmediated NO production is also consistent with previous studies that have demonstrated a suppressed NO component of flow-induced dilation in SHR (33,36,52) and in humans with hypertension (25) and coronary artery disease (51).…”

Section: Discussionsupporting

confidence: 92%

“…The presence of arterial disease and endothelial dysfunction are believed to alter NO and ROS levels to impact vasodilation and vascular structure. Although studies have demonstrated that flow elevation increases both NO (5,9,31) and ROS (37,43,51) production in arteries and arterioles, there is a lack of direct measurements of these reactive species under in vivo conditions, especially with flow alterations in the presence of arterial disease. Recent in vitro studies with arterioles from patients with arterial disease (43,51) have shown that H 2 O 2 increases with flow and mediates flow-dependent dilation.…”

Section: Nad(p)h Oxidase-derived Peroxide Mediates Elevated Basal Andmentioning

confidence: 99%

See 1 more Smart Citation

NAD(P)H oxidase-derived peroxide mediates elevated basal and impaired flow-induced NO production in SHR mesenteric arteries in vivo

Zhou¹,

Bohlen²,

Miller³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

Nitric oxide (NO) and reactive oxygen species (ROS) have fundamentally important roles in the regulation of vascular tone and remodeling. Although arterial disease and endothelial dysfunction alter NO and ROS levels to impact vasodilation and vascular structure, direct measurements of these reactive species under in vivo conditions with flow alterations are unavailable. In this study, in vivo measurements of NO and H2O2 were made on mesenteric arteries to determine whether antioxidant therapies could restore normal NO production in spontaneously hypertensive rats (SHR). Flow was altered from approximately 50-200% of control in anesthetized Wistar-Kyoto rats (WKY) and SHR by selective placement of microvascular clamps on adjacent arteries while NO and H2O2 were directly measured with microelectrodes. Relative to WKY, SHR had significantly increased baseline NO and H2O2 concentrations (2,572 +/- 241 vs. 1,059 +/- 160 nM, P < 0.01; and 26 +/- 7 vs. 7 +/- 1 microM, P < 0.05, respectively). With flow elevation, H2O2 but not NO increased in SHR; NO but not H2O2 was elevated in WKY. Apocynin and polyethylene-glycolated catalase decreased baseline SHR NO and H2O2 to WKY levels and restored flow-mediated NO production. Suppression of NAD(P)H oxidase with gp91ds-tat decreased SHR H2O2 to WKY levels. Addition of topical H2O2 to increase peroxide to the basal concentration measured in SHR elevated WKY NO to levels observed in SHR. The results support the hypothesis that increased vascular peroxide in SHR is primarily derived from NAD(P)H oxidase and increases NO concentration to levels that cannot be further elevated with increased flow. Short-term and even acute administration of antioxidants are able to restore normal flow-mediated NO signaling in young SHR.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Nad(p)h Oxidase-derived Peroxide Mediates Elevated Basal Andmentioning

confidence: 99%

NAD(P)H oxidase-derived peroxide mediates elevated basal and impaired flow-induced NO production in SHR mesenteric arteries in vivo

Zhou¹,

Bohlen²,

Miller³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…HSPs are also known to be upregulated by free radicals, including NO (45) and superoxide (15), and Sandau et al (28) have recently reviewed and reported evidence that HIF-1 can be activated by growth factors, cytokines, and NO. Production of NO and reactive oxygen species is increased with elevated flow or shear in arteries in vivo (10,16), and elevation of these free radicals could also explain the upregulation of HSPs and enolase in our model. Additonal studies are needed to investigate the role of these molecules in collateral development and to determine the specific mechanisms by which their expression is regulated, especially the role of shear stress, ischemia/ hypoxia, and free radicals.…”

Section: Discussionmentioning

confidence: 63%

Impaired collateral development in mature rats

Tuttle¹,

Hahn²,

Sanders³

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

The effect of maturation on collateral development of resistance arteries was investigated. Three to four sequential mesenteric arteries were ligated to create collateral pathways in anesthetized young (ϳ200 g) and mature (ϳ600 g) rats. Blood flow was similarly elevated in collaterals of young and mature animals. In vivo inner arterial diameter was increased only within young collaterals (33 Ϯ 7%, P Ͻ 0.001). Increases in number of intimal nuclei (57 Ϯ 10% vs. 52 Ϯ 14%) and cross-sectional medial area (33 Ϯ 13% vs. 38 Ϯ 5%) were similar between young and mature collaterals. Relative to the same animal controls, collateral endothelial nitric oxide synthase mRNA was increased as much in mature as in young rats. Proteomic analysis revealed significant differences in protein expression with maturation between control arteries as well as flow-loaded collateral vessels. The results indicate that, whereas intimal and medial remodeling events were similar in collaterals of young and mature rats, luminal expansion occurred only in young rats. Alteration in arterial protein expression with maturation and altered responses to stimuli for collateral development may contribute to this impairment. luminal expansion; resistance artery; proteomic analysis; eNOS; arterial remodeling DURING THE MATURATION OF PHYSIOLOGICAL SYSTEMS, many of the mechanisms governing various functional outcomes are altered. With increasing age, these alterations may in turn lead to functional impairments and exacerbate disease. The vascular system has been shown to follow this path with regard to a variety of functions, including blood vessel reactivity (20, 35) and vascular growth and remodeling (3,24,27). Studies from our laboratory have focused on understanding processes involved in collateral artery remodeling after chronic elevation of blood flow. Currently, little is known about how maturation and aging affect the capacity for collateral development. The clinical observation/experience is that collateral growth (32) and flow-induced luminal enlargement of arteries (8) occur in adult humans. However, flow-mediated remodeling in large conduit arteries, which has many mechanistic similarities to collateral/resistance artery remodeling, has been observed to be impaired with maturation (3, 24).Arterial remodeling occurs after chronic elevation of blood flow and is a complex process involving flow/ shear stimulus transduction and endothelial activation (5, 26). After transduction and activation, remodeling of the entire arterial wall is accomplished through changes in protein expression/activity and cell growth. Luminal dimensions are altered to normalize wall shear stress (3,24,40,46). Age-dependent alterations in any of the mechanisms involved in flow-induced arterial remodeling could influence the capacity for luminal adjustment in response to altered shear. The primary purpose of the current study was to determine whether flow-induced expansion of resistance arteries forming collateral pathways is impaired with maturation and to provide insight r...

show abstract

“…A series of studies have addressed whether flow is associated with increased NO formation in the mesenteric vascular bed [97, 98]. In the studies by Bohlen et al [97, 99, 100], NO concentration was measured by use of an NO-sensitive gold microelectrode, which was developed by Buerk et al [101], and situated close to the vessel wall of the intestine.…”

Section: Applicationsmentioning

confidence: 99%

“…Moreover, in rats, absorption of glucose was associated with an increased flow associated with doubling of the measured NO concentration [97, 99]. In dogs, where NO concentration was measured by use of a 200-µm carbon microsensor, the flow induced by occlusion of adjacent mesenteric arteries was also associated with a doubling of the NO concentration [98]. The application of two different microsensors shows that it is possible to obtain physiologically relevant information showing that increased flow is associated with increased NO concentration.…”

Section: Applicationsmentioning

confidence: 99%

Physiologically Relevant Measurements of Nitric Oxide in Cardiovascular Research Using Electrochemical Microsensors

2005

View full text Add to dashboard Cite

Nitric oxide (NO) plays an important role in the regulation of blood flow. Pharmacological tools and a series of other techniques have been developed for studying the NO/L-arginine pathway, but it has proved difficult to make a quantitative link between effect and tissue NO concentration. NO microsensors have been applied with success for the measurement of NO in suspensions of mitochondria and cells, such as platelets and leukocytes, and in cell cultures, which together with other interventions or measurements are particularly useful for the examination of cell signalling related to the NO/L-arginine pathway. In isolated vascular segments, studies using the NO microsensor have defined the relationship between NO concentration and relaxation and revealed residual NO release in the presence of NO synthase inhibitors. Moreover, simultaneous measurements of NO concentration and vasorelaxation in isometric preparations have shown that agonist-induced relaxation is L-arginine dependent and NO release is reduced in hypertension. By placing NO microsensors in catheters, it is possible to measure NO in the living animal and man. This approach has been applied for the measurements of NO concentration in relation to increases in flow, erection, in conditions of hypoxia, and in endotoxemia. However, further methodological development of NO microsensors is necessary to avoid the influence of changes in temperature, pH and oxygen on the measurements.

show abstract

Direct in vivo measurement of flow-dependent nitric oxide production in mesenteric resistance arteries

Cited by 16 publications

References 34 publications

NAD(P)H oxidase-derived peroxide mediates elevated basal and impaired flow-induced NO production in SHR mesenteric arteries in vivo

NAD(P)H oxidase-derived peroxide mediates elevated basal and impaired flow-induced NO production in SHR mesenteric arteries in vivo

Impaired collateral development in mature rats

Physiologically Relevant Measurements of Nitric Oxide in Cardiovascular Research Using Electrochemical Microsensors

Contact Info

Product

Resources

About