Attenuation of nitric oxide- and prostaglandin-independent vasodilation of retinal arterioles induced by acetylcholine in streptozotocin-treated rats

Nakazawa, Taisuke; Kaneko, Yu; Mori, Akira; Saito, Maki; Sakamoto, Kenji; Nakahara, Tsutomu; Ishii, Kunio

doi:10.1016/j.vph.2006.09.002

Cited by 51 publications

(45 citation statements)

References 28 publications

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“…For instance, early diabetes impacts glomerular permeability and glycocalyx alterations are reported in diabetic mice even before the development of albuminuria (46). In early diabetic retinopathy in rats and mice, both glycocalyx-and EDH-mediated vasodilation of retinal vessels are altered (47,48). Diabetic neuropathy in mice is accompanied by glycocalyx alteration in brain microvessels (49).…”

Section: Discussionmentioning

confidence: 99%

Hyaluronidase 1 Deficiency Preserves Endothelial Function and Glycocalyx Integrity in Early Streptozotocin-Induced Diabetes

et al. 2016

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Hyaluronic acid (HA) is a major component of the glycocalyx involved in the vascular wall and endothelial glomerular permeability barrier. Endocytosed hyaluronidase HYAL1 is known to degrade HA into small fragments in different cell types, including endothelial cells. In diabetes, the size and permeability of the glycocalyx are altered. In addition, patients with type 1 diabetes present increased plasma levels of both HA and HYAL1. To investigate the potential implication of HYAL1 in the development of diabetes-induced endothelium dysfunction, we measured endothelial markers, endothelium-dependent vasodilation, arteriolar glycocalyx size, and glomerular barrier properties in wild-type and HYAL1 knockout (KO) mice with or without streptozotocin (STZ)-induced diabetes. We observed that 4 weeks after STZ injections, the lack of HYAL1 1) prevents diabetes-induced increases in soluble P-selectin concentrations and limits the impact of the disease on endothelium-dependent hyperpolarization (EDH)-mediated vasorelaxation; 2) increases glycocalyx thickness and maintains glycocalyx structure and HA content during diabetes; and 3) prevents diabetes-induced glomerular barrier dysfunction assessed using the urinary albumin-to-creatinine ratio and urinary ratio of 70-to 40-kDa dextran. Our findings suggest that HYAL1 contributes to endothelial and glycocalyx dysfunction induced by diabetes. HYAL1 inhibitors could be explored as a new therapeutic approach to prevent vascular complications in diabetes.

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Section: Discussionmentioning

confidence: 99%

Hyaluronidase 1 Deficiency Preserves Endothelial Function and Glycocalyx Integrity in Early Streptozotocin-Induced Diabetes

et al. 2016

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“…41,42) We also found that, in a previous study, vasodilation of retinal arterioles to acetylcholine, but not to forskolin and sodium nitroprusside, was reduced in streptozotocin-induced diabetic rats. 37) These results suggest that diabetes impairs endothelium-dependent vasodilation of retinal blood vessels. Therefore, if CRF 2 receptor-mediated vasodilation is endothelium-dependent, diabetes would reduce the vasodilator effect of urocortin or urocortin 2 on retinal arterioles by impairing endothelial cell functions.…”

Section: Discussionmentioning

confidence: 91%

“…36,37) Briefly, we selected the green channel image, which could provide the greatest contrast among three individual color channels (red, green and blue). To make the analysis easier, we obtained the greatest contrast of retinal blood vessels by altering the brightness of the green channel image.…”

Section: Measurement Of Diameters Of Retinal Blood Vesselsmentioning

confidence: 99%

Vasodilation of Retinal Arteriole Mediated by Corticotropin-Releasing Factor Receptor is Impaired in Streptozotocin-Induced Diabetic Rats

Kaneko

Saito

Mori

et al. 2007

Biological & Pharmaceutical Bulletin

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Diabetic retinopathy is the most common complication of diabetes and is a leading cause of blindness in industrialized countries. A progression of histological and physiological abnormalities of the retinal circulation leads to the blindness that results from diabetic retinopathy.1,2) The vascular abnormalities, such as an alteration of responsiveness of retinal blood vessels and breakdown of the blood-retinal barrier, have been widely documented in patients and experimental animals with diabetes.1-5) Circulating hormones and local factors released from endothelial cells 6,7) and retinal tissues 8,9) might play an important role in the maintenance of vascular function in retinal circulation, because of lack of autonomic innervation. Therefore, it is important to examine effects of diabetes on vascular responses to circulating hormones and local factors in retinal circulation.Urocortin (now known as urocortin 1) is a 40-amino acid peptide that belongs to the family of corticotropin-releasing factor (CRF), 10) which is also known as corticotropin-releasing hormone.11,12) Recently, two 38-amino acid isoforms of urocortin are identified (i.e., urocortin 2 and urocortin 3). 13,14) The actions of these peptides are mediated through the activation of two G protein-coupled receptor subtypes that are coupled to adenylyl cyclase; corticotropin-releasing factor type 1 (CRF 1 ) receptor and corticotropin-releasing factor type 2 (CRF 2 ) receptor.10,15-17) CRF shows higher affinity for CRF 1 than CRF 2 receptors, whereas urocortin has an equal affinity for CRF 1 and CRF 2 receptors. Both urocortin 2 and urocortin 3 bind selectively to CRF 2 receptors. 18)Urocortins exhibit several in vivo cardiovascular effects including hypotension and tachycardia. [19][20][21][22][23] In addition, the in vitro studies have demonstrated that urocortins relax the isolated blood vessel preparations, such as coronary, basilar, renal and tail arteries, etc. [24][25][26][27][28][29][30][31] These cardiovascular effects of urocortins were predominantly mediated by CRF 2 receptors. [20][21][22][32][33][34] However, it remains to be determined the effects of stimulation of CRF 2 receptors on retinal circulation and how diabetes affects the vasodilator actions on retinal blood vessels. Therefore, in the present study, we examined 1) whether urocortin and urocortin 2 dilate retinal arterioles in vivo and 2) whether diabetes affects the in vivo vasodilator responses to urocortins of retinal arterioles using streptozotocin-induced diabetic rats. MATERIALS AND METHODS Animal Model of DiabetesMale Wistar rats weighting 230-250 g were maintained on standard rat chow and tap water ad libitum with 12 : 12-h dark cycle in a quiet environment. Diabetes was induced by a single intravenous injection of streptozotocin (65 mg/kg) dissolved in sodium citrate buffer (pH 4.5). Age-matched control rats were treated with an injection of an equal volume of vehicle. Induction of diabetes was confirmed with blood glucose measurements (Ͼ300 mg/dl) 24 h after streptozotoci...

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“…Both responses to ACh were significantly diminished 6 -8 weeks after induction of hyperglycemia in streptozotocin (STZ)-treated rats (6,7). More recently, we showed that in an early stage of diabetes (2-week duration of diabetes) the vasodilation of retinal arterioles, but not the depressor response, to ACh were significantly reduced by inducing more severe hyperglycemia by giving Dglucose as drinking water after STZ treatment (8).…”

Section: Introductionmentioning

confidence: 90%

“…We previously found that intravenously administered acetylcholine (ACh) increases the retinal arteriolar diameter but decreases systemic blood pressure in rats (6,7). Both responses to ACh were significantly diminished 6 -8 weeks after induction of hyperglycemia in streptozotocin (STZ)-treated rats (6,7).…”

Section: Introductionmentioning

confidence: 99%

Hyperglycemia Impairs Acetylcholine-Induced Vasodilation of Retinal Arterioles Through Polyol Pathway–Independent Mechanisms in Rats

et al. 2010

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Abstract. We previously reported that acetylcholine (ACh)-induced vasodilation of retinal arterioles is diminished in diabetic rats; however, the underlying mechanism(s) of this phenomenon has not been fully elucidated. To determine the role of the polyol pathway in the diabetes-induced retinal vascular dysfunction, we investigated the effect of GP-1447, an inhibitor of aldose reductase, on the attenuation of ACh-induced vasodilation of retinal arterioles seen in diabetic rats. Male Wistar rats were treated with streptozotocin (STZ) and experiments were performed 2 weeks later. The STZ-treated animals were given drinking water containing 5% D-glucose to shorten the term for the development of retinal vascular dysfunction. Treatment with GP-1447 was initiated immediately after STZ treatment and continued throughout the 2-week experimental period. The attenuation of retinal vascular responses to ACh were not modified by treatment with GP-1447, whereas the aldose reductase inhibitor completely prevented diabetes-induced thinning of the retina and sorbitol accumulation in the retina and the lens. These results suggest that mechanisms that are independent of the polyol pathway may contribute to the onset of retinal endothelial dysfunction, although the pathway plays an important role in morphological changes of retina and formation of cataracts in diabetic rats.

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Attenuation of nitric oxide- and prostaglandin-independent vasodilation of retinal arterioles induced by acetylcholine in streptozotocin-treated rats

Cited by 51 publications

References 28 publications

Hyaluronidase 1 Deficiency Preserves Endothelial Function and Glycocalyx Integrity in Early Streptozotocin-Induced Diabetes

Hyaluronidase 1 Deficiency Preserves Endothelial Function and Glycocalyx Integrity in Early Streptozotocin-Induced Diabetes

Vasodilation of Retinal Arteriole Mediated by Corticotropin-Releasing Factor Receptor is Impaired in Streptozotocin-Induced Diabetic Rats

Hyperglycemia Impairs Acetylcholine-Induced Vasodilation of Retinal Arterioles Through Polyol Pathway–Independent Mechanisms in Rats

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