Abstract:
BACKGROUND AND PURPOSE:Diabetes is a risk factor for the development of coronary artery disease but it is not known whether the functions of endothelium-derived nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in coronary arteries are altered in the early stage of diabetes. Such alterations and the effects of pravastatin were examined in left anterior descending coronary arteries (LAD) from Otsuka Long-Evans Tokushima Fatty (OLETF) rats (type 2 diabetes model) at the early hyperglycaemic stage [vs. non-diabetic Long-Evans Tokushima Otsuka (LETO) rats]. EXPERIMENTAL APPROACH:Isometric tension, membrane potential and superoxide production were measured, as were protein expression of NAD(P)H oxidase components and endothelial NO synthase (eNOS). KEY RESULTS:Superoxide production and the protein expressions of both the nicotinamide adenine dinucleotide (phosphate) [NAD(P)H] oxidase components and eNOS were increased in OLETF rats. These changes were normalized by pravastatin administration. Not only acetylcholine (ACh)-induced endothelial NO production but also functions of endothelium-derived NO [from (i) the absolute tension induced by epithio-thromboxane A(2) (STA(2)) or high K(+); (ii) enhancement of the STA(2)-contraction by a nitric oxide synthase (NOS) inhibitor; and (iii) the ACh-induced endothelium-dependent relaxation of high K(+)-induced contraction] or EDHF [from (iv) ACh-induced endothelium-dependent smooth muscle cell hyperpolarization and relaxation in the presence of a NOS inhibitor] were similar between LETO and OLETF rats [whether or not the latter were pravastatin-treated or -untreated]. CONCLUSIONS AND IMPLICATIONS:Under conditions of increased vascular superoxide production, endothelial function is retained in LAD in OLETF rats at the early hyperglycaemic stage, partly due to enhanced endothelial NOS protein expression. Inhibition of superoxide production may contribute to the beneficial vascular effects of pravastatin.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Kajikuri J,Watanabe Y,Ito Y,Ito R,Yamamoto T,Itoh Tdoi
10.1111/j.1476-5381.2009.00348.xsubject
Has Abstractpub_date
2009-09-01 00:00:00pages
621-32issue
2eissn
0007-1188issn
1476-5381pii
BPH348journal_volume
158pub_type
杂志文章abstract::This work investigates the receptor acted upon by imidazoline compounds in the modulation of morphine analgesia. The effects of highly selective imidazoline ligands on the supraspinal antinociception induced by morphine in mice were determined. 2. Intracerebroventricular (i.c.v.) or subcutaneous (s.c.) administration ...
journal_title:British journal of pharmacology
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1980.tb10696.x
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