Changes in responsiveness of the aorta to vasorelaxant agents in genetically diabetic rats: A study in WBN/KOB rats

Miyata, Noriyuki; Yamaura, Hiroko; Tsuchida, Katsuharu; Otomo, Susumu; Kamata, Katsuo; Kasuya, Yutaka

doi:10.1016/0024-3205(92)90287-y

Cited by 14 publications

(4 citation statements)

References 12 publications

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“…We have also found that denuding the endothelium mechanically decreased the vasorelaxant response of IP. This suggests that β 2 ‐adrenoceptors are present in vascular endothelium and attenuation of β 2 ‐adrenoceptor‐mediated vasorelaxant response in various vascular diseases like hypercholesterolaemia [39,41,42]. Thus, β 2 ‐adrenoceptor‐mediated vasorelaxation is partially dependent on the existence of endothelial cell [43].…”

Section: Discussionmentioning

confidence: 99%

Antioxidative Action of Aspirin on Endothelial Function in Hypercholesterolaemic Rats

Tauseef

Shahid

Sharma

et al. 2008

Basic Clin Pharma Tox

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The role of aspirin on vascular endothelial changes during hypercholesterolaemia prior to development of actual atherosclerotic lesions is not known. Therefore, in the present study, we tested the hypothesis that aspirin by its antioxidant action improves endothelial function in a rat model of hypercholesterolaemia. Hypercholesterolaemia was induced in Wistar rats by feeding a 1% cholesterol-rich diet for 10 weeks. Lipid profile, lipid peroxidation and reduced glutathione were estimated in serum. Endothelial function and β 2 -adrenoceptor activity was tested by studying the dose-response relationship of acetylcholine and isoproterenol, respectively, on isolated aortic tissues in an organ bath setup. Hypercholesterolaemic rats showed a significant increase in total cholesterol, low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C), and a significant fall in high-density lipoprotein cholesterol (HDL-C) compared to the control rats. Isolated aortic tissues from hypercholesterolaemic rats showed endothelial dysfunction and decreased sensitivity to β 2 -adrenoceptor. Treatment with aspirin was associated with a fall in total cholesterol, LDL-C and VLDL-C, and a significant rise in serum HDL-C. Aspirin treatment also restored endothelial function and β 2 -adrenoceptor activity. Hypercholesterolaemic rats showed free radical generation, evident by increase in serum lipid peroxidation and reduction in serum reduced glutathione content compared to the control rats. Aspirin treatment was associated with reduction in free radical stress evident by decreased lipid peroxidation and significantly prevented reduction in glutathione content compared to hypercholesterolaemic controls. Aspirin improves endothelial function and β 2 -adrenoceptor activity during experimentally induced hypercholesterolaemia in rats, possibly due to an antioxidant effect.

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Section: Discussionmentioning

confidence: 99%

Antioxidative Action of Aspirin on Endothelial Function in Hypercholesterolaemic Rats

Tauseef

Shahid

Sharma

et al. 2008

Basic Clin Pharma Tox

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“…123 One study in the aorta of WBN/Kob rat showed no alteration in relaxation to the K ATP channel agonist cromakalim. 124 In contrast, others have observed a paradoxically enhanced response in dog coronaries to aprikalim, albeit in short-term diabetes. 125 In normal arteries, it is generally believed that the component of EDHF versus NO that contributes to total relaxation increases with decreasing vessel size.…”

Section: No-dependent or -Independent Endothelial Dysfunctionmentioning

confidence: 96%

Review of Alterations in Endothelial Nitric Oxide Production in Diabetes

1998

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N itric oxide release from the endothelium plays an important role in regulation of vascular tone, 1 inhibition of both platelet and leukocyte aggregation and adhesion, 1,2 and inhibition of cell proliferation.3 These properties suggest that the level of NO production by the endothelium may play a pivotal role in the regulation of vascular disease. Analysis using mass spectrometry has revealed that NO is produced by NOS from the terminal guanidino nitrogen of the precursor amino acid L-arginine. 4 Thus, utilization of L-arginine and conversion to NO may establish a regulatory site in the development of endothelial dysfunction.Endothelial dysfunction is characterized by defective endothelium-dependent relaxation, and some reviews regarding endothelial dysfunction in diabetes have been published. [5][6][7][8] These reviews have focused on factors that might contribute to defective relaxation, some of which will not be addressed in detail in this review. The purpose of the present review is to summarize evidence that specifically supports either decreased NO production by diabetic vascular endothelium and/or impaired NO-mediated endothelium-dependent relaxation. Second, this review provides reasonable alternatives to explain some of the controversies in this research area. Third, since there is growing evidence that arginine appears to have some benefits for diabetes-associated abnormalities, this review summarizes the current state of knowledge of effects of acute and chronic administration of L-arginine on diabetesinduced endothelial dysfunction and discusses potential NOdependent and -independent mechanisms whereby therapeutic intervention with L-arginine might benefit the diabetic endothelium. Impaired Endothelium-Dependent Relaxation Experimental Diabetes MellitusDecreases in endothelium-dependent relaxation are a common feature in both conduit 9 -20 and resistance 21-30 arteries of chemically induced experimental diabetic animals (including rats, mice, rabbits, hamsters, and dogs). In two genetic models of IDDM, similar impaired relaxation has been documented in aorta [31][32][33] and mesenteric arteries 34,35 of diabetes-prone BB/Wor or BB/E rats and in aorta 36 and mesenteric arteries 37 of the diabetes-prone WBN/Kob rat. Almost without exception, studies that have shown impaired endothelium-dependent relaxation have found normal relaxation to nitrovasodilators. These agents relax vascular smooth muscle by activating guanylate cyclase but, unlike NO, do not require the presence of the endothelium. Thus, the intrinsic property to activate vascular smooth muscle guanylate cyclase appears not to be altered by experimental diabetes.Studies in experimental models of NIDDM are few and controversial. In the obese Zucker rat, no alteration in endothelium-dependent relaxation has been observed in intestinal microvessels, 38 whereas increased reactivity has been observed in aorta. 39,40 In contrast, decreased endotheliumdependent relaxation to acetylcholine but not to A23187 was seen in aorta in male (but not female)...

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“…Consideration of methods. Many previous studies have examined the effects of activation of ATP-sensitive potassium channels on large peripheral and cerebral blood vessels in vitro (26,28,33,(38)(39)(40)43) and in vivo (9,11,52,55). In addition, Mayhan (34) and other investigators (52) have examined the effects of activation of ATP-sensitive potassium channels on peripheral resistance arterioles.…”

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confidence: 99%

Effect of cigarette smoke extract on arteriolar dilatation in vivo

Mayhan

Sharpe

1996

Journal of Applied Physiology

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The goal of this study was to determine whether cigarette smoke extract alters dilatation of arterioles in vivo in response to agonists that produce activation of ATP-sensitive potassium channels and activation of adenylate cyclase. By using intravital microscopy, we measured diameter of arterioles contained within the microcirculation of the hamster cheek pouch during suffusion with agonists in the absence and presence of cigarette smoke extract (0.1, 0.5, and 1.0%). Before treatment with cigarette smoke extract, activation of ATP-sensitive potassium channels with aprikalim and cromakalim produced dose-related dilatation of cheek pouch arterioles. Similarly, activation of adenylate cyclase with isoproterenol and forskolin produced dose-related dilatation of cheek pouch arterioles before treatment with cigarette smoke extract. Superfusion of 0.1% cigarette smoke extract did not change baseline diameter of arterioles and did not alter responses of cheek pouch arterioles to activation of ATP-sensitive potassium channels and adenylate cyclase. Superfusion of 0.5 and 1.0% cigarette smoke extract also did not alter baseline diameter of arterioles but did impair dilatation of arterioles in response to activation of ATP-sensitive potassium channels and adenylate cyclase. These findings suggest that cigarette smoke extract impairs dilatation of resistance arterioles in response to activation of important cellular dilator pathways.

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Changes in responsiveness of the aorta to vasorelaxant agents in genetically diabetic rats: A study in WBN/KOB rats

Cited by 14 publications

References 12 publications

Antioxidative Action of Aspirin on Endothelial Function in Hypercholesterolaemic Rats

Antioxidative Action of Aspirin on Endothelial Function in Hypercholesterolaemic Rats

Review of Alterations in Endothelial Nitric Oxide Production in Diabetes

Effect of cigarette smoke extract on arteriolar dilatation in vivo

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