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Titolo:
Neurovascular interactions between aldose reductase and angiotensin-converting enzyme inhibition in diabetic rats
Autore:
Cotter, MA; Mirrlees, DJ; Cameron, NE;
Indirizzi:
Univ Aberdeen, Inst Med Sci, Dept Biomed Sci, Aberdeen AB25 2ZD, Scotland Univ Aberdeen Aberdeen Scotland AB25 2ZD ci, Aberdeen AB25 2ZD, Scotland AstraZeneca Pharmaceut, Macclesfield, Cheshire, England AstraZeneca Pharmaceut Macclesfield Cheshire England , Cheshire, England
Titolo Testata:
EUROPEAN JOURNAL OF PHARMACOLOGY
fascicolo: 3, volume: 417, anno: 2001,
pagine: 223 - 230
SICI:
0014-2999(20010413)417:3<223:NIBARA>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
ENDONEURIAL BLOOD-FLOW; ALPHA-LIPOIC ACID; NITRIC-OXIDE; CORPUS CAVERNOSUM; NERVE-CONDUCTION; POLYOL PATHWAY; SORBITOL DEHYDROGENASE; OXYGEN-TENSION; AORTIC RINGS; VITAMIN-E;
Keywords:
neuropathy; diabetic; rat; aldose reductase; angiotensin-converting enzyme; nerve conduction; blood flow;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Cameron, NE Univ Aberdeen, Inst Med Sci, Dept Biomed Sci, Foresterhill, Aberdeen AB25 2ZD, Scotland Univ Aberdeen Foresterhill Aberdeen Scotland AB25 2ZD cotland
Citazione:
M.A. Cotter et al., "Neurovascular interactions between aldose reductase and angiotensin-converting enzyme inhibition in diabetic rats", EUR J PHARM, 417(3), 2001, pp. 223-230

Abstract

Increased polyol pathway flux has been linked to nerve complications in diabetic rats, which are attenuated by aldose reductase inhibitors, defectivenitric oxide-mediated vasodilation being a particular target. Diabetes also elevates the endothelial angiotensin system, increasing vasa nervorum vasoconstriction. The aim was to assess whether promotion of vasodilation by treatment with the aldose reductase inhibitor, ZD5522 (3 ' ,5 ' -dimethyl-4 ' -nitromethylsulphonyl-2-(2-toyl)acretanilide coupled with reduced vasoconstriction using the angiotensin-converting enzyme inhibitor, lisinopril, interacted positively to improve neurovascular function. After 8 weeks of streptozotocin-induced diabetes, sciatic nerve blood flow and motor conductionvelocity were 51% and 21% reduced, respectively. Two weeks of Lisinopril treatment dose-dependently corrected the conduction deficit (ED50 similar to0.9 mg kg(-1)). Low-dose Lisinopril (0.3 mg kg(-1)) or ZD5522 (0.25 mg kg(-1)) had modest corrective (10-20%) effects on nerve conduction and perfusion. However, when combined, blood flow and conduction velocity reached the nondiabetic range. The ZD5522 dose used gave a similar to 45% nerve sorbitol reduction but had no significant effect on fructose content; lisinopril co-treatment did not alter ZD5522 action on polyols. Thus, there was a marked neurovascular synergistic interaction between angiotensin-converting enzyme and aldose reductase inhibition in diabetic rats. This points to a potential therapeutic benefit, which requires evaluation in clinical trials. (C)2001 Elsevier Science B.V. All rights reserved.

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Documento generato il 04/12/20 alle ore 08:53:08