Altered vasodilator role of nitric oxide synthase in the pancreas, heart and brain of rats with spontaneous type 2 diabetes

Song, Dongzhe; Yao, Reina; Pang, Catherine C.Y.

doi:10.1016/j.ejphar.2008.06.036

Cited by 15 publications

(9 citation statements)

References 29 publications

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“…This finding is well in line with previous studies in the STZ-rat [20]. Generalized vasoconstriction following inhibition of NO synthesis, although to a different extent in various tissues, has also been observed in other rat models of diabetes, such as the Zucker diabetic fatty rat [21] as well as in the ocular circulation of diabetic humans [22]. …”

Section: Discussionsupporting

confidence: 91%

Endothelin-induced changes in blood flow in STZ-diabetic and non-diabetic rats: relation to nitric oxide synthase and cyclooxygenase inhibition

Granstam

2011

J Physiol Sci

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In this study, using the microsphere method, the hemodynamic response to endothelin-1 (ET-1) in healthy and streptozotocin (STZ)-diabetic rats was evaluated as well as the influences of inhibition of nitric oxide (NO)-synthase using L-NAME (Nω-nitro-l-arginine methyl ester) and the cyclooxygenase inhibitor indomethacin. Blood flow (Q) was measured in tissues of interest for vascular complications in diabetes such as kidney, eye, brain, heart and skeletal muscle with the main focus on ophthalmic circulation. Under resting conditions, evidence for renal vasoconstriction was found in diabetic animals. In both groups, administration of L-NAME reduced Q in all investigated tissues indicating a basal NO influence. In the normal rats, ET-1 induced a significant increase in blood pressure and intense vasoconstriction in all tissues except in the choroid of the eye and in the brain, where it induced an increased Q. In the STZ-diabetic rats, effects of ET-1 were less pronounced. Pretreatment with L-NAME, but not the cyclooxygenase inhibitor, abolished the ET-1-induced vasodilation in the choroid of both groups. Administration of ET A receptor antagonist BQ-123 reduced the ET-1-induced vasodilation in the choroid only in diabetic animals. In conclusion, evidence for altered vascular endothelial response to ET-1 in STZ-diabetic animals was found particularly in the ophthalmic circulation. The findings suggest differential involvement of receptors in the response to ET-1 in normal and STZ-diabetic animals.

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Section: Discussionsupporting

confidence: 91%

Endothelin-induced changes in blood flow in STZ-diabetic and non-diabetic rats: relation to nitric oxide synthase and cyclooxygenase inhibition

Granstam

2011

J Physiol Sci

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“…One of the molecular actors of inflammation is nitric oxide (NO). Depending on the level of NO secreted by the cells, this gaseous diffusible factor may have physiological benefits (2,34) or deleterious effects on type 2 diabetes (23). Interestingly, low concentrations of NO, as induced by activation of constitutive nitric oxide synthase (NOS), protect against ER stress, as opposed to massive NO release by iNOS (11).…”

Section: Introductionmentioning

confidence: 99%

Jejunum Inflammation in Obese and Diabetic Mice Impairs Enteric Glucose Detection and Modifies Nitric Oxide Release in the Hypothalamus

Duparc

Naslain

Colom

et al. 2011

Antioxidants & Redox Signaling

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Intestinal detection of nutrients is a crucial step to inform the whole body of the nutritional status. In this paradigm, peripheral information generated by nutrients is transferred to the brain, which in turn controls physiological functions, including glucose metabolism. Here, we investigated the effect of enteric glucose sensors stimulation on hypothalamic nitric oxide (NO) release in lean or in obese/diabetic (db/db) mice. By using specific NO amperometric probes implanted directly in the hypothalamus of mice, we demonstrated that NO release is stimulated in response to enteric glucose sensors activation in lean but not in db/db mice. Alteration of gut to hypothalamic NO signaling in db/db mice is associated with a drastic increase in inflammatory, oxidative/nitric oxide (iNOS, IL-1β), and endoplasmic reticulum stress (CHOP, ATF4) genes expression in the jejunum. Although we could not exclude the importance of the hypothalamic inflammatory state in obese and diabetic mice, our results provide compelling evidence that enteric glucose sensors could be considered as potential targets for metabolic diseases.

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“…In rats with type 1 diabetes, we have recently found pulmonary endothelial dysfunction associated to increased superoxide production and upregulation of the NADPH oxidase subunit p47 phox [8]. The Obese Zucker rat is a well establish model of obesity and insulin resistance associated to systemic vascular dysfunction [22-24]. Nonetheless, the pulmonary vasculature remains uncharacterized in this model.…”

Section: Introductionmentioning

confidence: 99%

Pulmonary arterial dysfunction in insulin resistant obese Zucker rats

et al. 2011

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BackgroundInsulin resistance and obesity are strongly associated with systemic cardiovascular diseases. Recent reports have also suggested a link between insulin resistance with pulmonary arterial hypertension. The aim of this study was to analyze pulmonary vascular function in the insulin resistant obese Zucker rat.MethodsLarge and small pulmonary arteries from obese Zucker rat and their lean counterparts were mounted for isometric tension recording. mRNA and protein expression was measured by RT-PCR or Western blot, respectively. KV currents were recorded in isolated pulmonary artery smooth muscle cells using the patch clamp technique.ResultsRight ventricular wall thickness was similar in obese and lean Zucker rats. Lung BMPR2, KV1.5 and 5-HT2A receptor mRNA and protein expression and KV current density were also similar in the two rat strains. In conductance and resistance pulmonary arteries, the similar relaxant responses to acetylcholine and nitroprusside and unchanged lung eNOS expression revealed a preserved endothelial function. However, in resistance (but not in conductance) pulmonary arteries from obese rats a reduced response to several vasoconstrictor agents (hypoxia, phenylephrine and 5-HT) was observed. The hyporesponsiveness to vasoconstrictors was reversed by L-NAME and prevented by the iNOS inhibitor 1400W.ConclusionsIn contrast to rat models of type 1 diabetes or other mice models of insulin resistance, the obese Zucker rats did not show any of the characteristic features of pulmonary hypertension but rather a reduced vasoconstrictor response which could be prevented by inhibition of iNOS.

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Altered vasodilator role of nitric oxide synthase in the pancreas, heart and brain of rats with spontaneous type 2 diabetes

Cited by 15 publications

References 29 publications

Endothelin-induced changes in blood flow in STZ-diabetic and non-diabetic rats: relation to nitric oxide synthase and cyclooxygenase inhibition

Endothelin-induced changes in blood flow in STZ-diabetic and non-diabetic rats: relation to nitric oxide synthase and cyclooxygenase inhibition

Jejunum Inflammation in Obese and Diabetic Mice Impairs Enteric Glucose Detection and Modifies Nitric Oxide Release in the Hypothalamus

Pulmonary arterial dysfunction in insulin resistant obese Zucker rats

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