Growth-related changes in the influence  of nitric oxide on arteriolar tone

Linderman, J. Russell; Boegehold, Matthew A.

doi:10.1152/ajpheart.1999.277.4.h1570

Cited by 23 publications

(51 citation statements)

References 33 publications

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“…6) suggests that inhibition of Cu/Zn SOD activity, with or without simultaneous catalase inhibition, increases O – 2 to a level that inhibits NO-dependent relaxation. Arteriolar responses to ACh are only partly mediated by NO in rat spinotrapezius muscle, and the extent to which Cu/Zn SOD inhibition reduced ACh responses in this study is virtually identical to the reduction in ACh responses of these vessels after complete NO synthase inhibition [5, 40]. Our finding that SOD inhibition decreases endothelium-dependent dilation is consistent with findings in other vessel types [34, 35, 41].…”

Section: Discussionsupporting

confidence: 90%

Effect of a High Salt Diet on Microvascular Antioxidant Enzymes

Lenda

Boegehold²

2002

J Vasc Res

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High dietary salt intake decreases the endothelium-dependent dilation of skeletal muscle arterioles by inhibiting local nitric oxide (NO) activity without changing vascular smooth muscle responsiveness to NO. Under these conditions, microvascular walls show evidence of oxidative stress, and scavengers of reactive oxygen species (ROS) abolish this oxidative stress and restore normal arteriolar responses to acetylcholine (ACh). We tested the hypothesis that the salt-dependent appearance of microvascular ROS, and accompanying reduction in endothelium-dependent dilation, is due to a decrease in antioxidant enzyme expression or activity. We studied spinotrapezius muscle microvessels in rats fed normal (NS) (0.45%) or high (HS) (7%) salt diets for 4–5 weeks. Western analysis of arteriolar and venular protein showed no difference between groups in the content of superoxide dismutase (Cu/Zn SOD), catalase, or glutathione peroxidase. The catalase inhibitor 3-amino-1,2,4-triazole (3AT) increased arteriolar and venular oxidant activity (assessed by tetranitroblue tetrazolium reduction) by the same amount in both groups, suggesting similar levels of catalase activity. 3AT did not affect arteriolar responses to ACh in either group. The Cu/Zn SOD inhibitor diethyldithiocarbamate increased arteriolar and venular oxidant activity to a lesser extent in HS rats, suggesting reduced Cu/Zn SOD activity in this group. Cu/Zn SOD inhibition decreased arteriolar responses to ACh only in NS rats. These findings suggest that endogenous Cu/Zn SOD preserves the endothelium-dependent control of arteriolar tone in NS rats, and that a reduction in Cu/Zn SOD activity contributes to the loss of arteriolar NO activity in HS rats.

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Section: Discussionsupporting

confidence: 90%

Effect of a High Salt Diet on Microvascular Antioxidant Enzymes

Lenda

Boegehold²

2002

J Vasc Res

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“…Therefore, age-dependent changes in the contribution of CO to these responses appear to be complete by the time the animal reaches 6–7 weeks of age. Similarly, previous studies from our laboratory have demonstrated that the ability of the arteriolar endothelium to release NO in response to shear stress increases dramatically from the weanling to the juvenile stage, but does not change further from the juvenile to the adult stage [4]. Taken in aggregate, these findings suggest that with respect to the endothelium-dependent control of arteriolar tone, the adult phenotype appears to be established by 6–7 weeks of age.…”

Section: Discussionsupporting

confidence: 79%

“…Growth-related changes in microvascular endothelial function have been reported by our laboratory and others [1, 4, 36]. In our recent investigations on gracilis muscle arterioles [1, 2], we ruled out NO, prostanoids, cytochrome P-450 metabolites and H 2 O 2 as possible mediators of endothelium-dependent dilation to various agonists in young (weanling) rats.…”

Section: Discussionmentioning

confidence: 82%

“…Endothelium-dependent dilation was elicited by application of ACh or simvastatin (Merck Research Laboratories, Rahway, N.J., USA) at bath concentrations of 10 –5 or 10 –7 M [3, 4]. Simvastatin was first activated by alkaline lysis (5.25 ml of 0.1 N NaOH per 140 mg, dissolved in 3.5 ml of ETOH) at 50°C for 2 h. The resulting solution was then diluted to a volume of 35 ml with PBS, and neutralized to pH 7.4 with HCl.…”

Section: Methodsmentioning

confidence: 99%

“…Studies from our laboratory have documented that postnatal growth of the microvasculature is accompanied by progressive changes in a number of factors that can influence arteriolar tone and blood flow [1,2,3,4]. For example, skeletal muscle arterioles from young rats exhibit fully developed endothelium-dependent dilation, but these responses are not mediated by nitric oxide (NO), cyclooxygenase metabolites or hydrogen peroxide (H 2 O 2 ), as they are in arterioles from more mature rats [1, 2].…”

Section: Introductionmentioning

confidence: 99%

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Growth-Dependent Changes in the Contribution of Carbon Monoxide to Arteriolar Function

Samora

Goodwill²,

Frisbee³

et al. 2009

J Vasc Res

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Background/Aims: Endothelium-dependent dilation of skeletal muscle arterioles is mediated by unknown factors in very young rats. We assessed the possible contribution of carbon monoxide (CO) to this dilation and to dilation in older animals. Methods: The effects of de-endothelialization or various pharmacological inhibitors on responses to CO or endothelium-dependent dilators were studied in gracilis muscle arterioles from rats at 3–4 weeks (‘weanlings’) and 6–7 weeks (‘juveniles’). Results: Exogenous CO constricted, rather than dilated, arterioles from both age groups. This constriction was reduced by endothelial removal or NOS inhibition in juvenile, but not weanling, arterioles. In contrast, this constriction was abolished by K⁺ channel inhibition in weanling, but not juvenile, arterioles. The heme precursor δ-aminolevulinic acid constricted juvenile arterioles but did not affect weanling arterioles. The heme oxygenase inhibitor chromium (III) mesoporphyrin IX abolished the endothelium-dependent dilation of juvenile arterioles to simvastatin, and reduced ACh- and simvastatin-induced dilations of weanling arterioles. Conclusion: These findings suggest that relatively high concentrations of exogenous CO can cause constriction by inhibiting endothelium-derived NO in juvenile arterioles and inhibiting K⁺ channels in weanling arterioles. Endogenous CO produced at lower concentrations can contribute to endothelium-dependent dilation in both age groups.

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Developmental Conditioning of the Vasculature

Clough

2014

Comprehensive Physiology

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There is increasing evidence from epidemiological and experimental animal studies that the early life environment, of which nutrition is a key component, acts through developmental adaptive responses to set the capacity of cardiovascular and metabolic pathways to respond to physiological and pathophysiological challenges in later life. One finding that is consistent to both population studies and animal models is the propensity for such effects to induce endothelial dysfunction throughout the vascular tree, including the microvasculature. Obesity, type 2 diabetes and hypertension are associated with changes in microvascular function affecting multiple tissues and organs. These changes may be detected early, often before the onset of macrovascular disease and the development of end organ damage. Suboptimal maternal nutrition and fetal growth result in reduced microvascular perfusion and functional dilator capacity in the offspring, which together with microvascular rarefaction and remodeling serve to limit capillary recruitment, reduce exchange capacity and increase diffusion distances of metabolic substrates; they also increase local and overall peripheral resistance. This article explores how a developmentally conditioned disadvantageous microvascular phenotype may represent an important and additional risk factor for increased susceptibility to the development of cardio-metabolic disease in adult life and considers the cell signaling pathways associated with microvascular dysfunction that may be "primed" by the maternal environment. As the microvasculature has been shown to be a potential target for early therapeutic and lifestyle intervention, this article also considers evidence for the efficacy of such strategies in humans and in animal models of the developmental origins of health and disease.

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Growth-related changes in the influence of nitric oxide on arteriolar tone

Cited by 23 publications

References 33 publications

Effect of a High Salt Diet on Microvascular Antioxidant Enzymes

Effect of a High Salt Diet on Microvascular Antioxidant Enzymes

Growth-Dependent Changes in the Contribution of Carbon Monoxide to Arteriolar Function

Developmental Conditioning of the Vasculature

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