The effects of aldose reductase inhibition with ponalrestat on changes in vascular function in streptozotocin diabetic rats

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Abstract

The responses of rat isolated aortae to vasoconstrictor and vasodilator agents have been studied in 14‐day streptozotocin‐diabetic rats. The effects of treatment with the aldose reductase inhibitor, ponalrestat, on these responses have also been investigated. Maximum contractile responses and aortic sensitivity to phenylephrine were significantly enhanced in 14‐day diabetic aortae. In contrast, endothelium‐dependent relaxations to carbachol were depressed in diabetic rats, whilst endothelium‐independent relaxations to forskolin and sodium nitroprusside were unchanged. Pretreatment with ponalrestat (25 mg kg−1, daily) prevented both the enhanced maximum contractile responses to phenylephrine and the depressed endothelium‐dependent relaxations to carbachol in aortae from 14‐day diabetic rats. Ponalrestat however, had no effect on the reduced phenylephrine EC50 values observed in tissues from diabetic animals. It is concluded that ponalrestat prevents the depression of endothelium‐dependent aortic relaxations induced by diabetes of 14 days duration, suggesting that the polyol pathway is involved in these vascular changes. Ponalrestat does not prevent the increase in aortic sensitivity to α1adrenoceptor agonists. 1994 British Pharmacological Society

Original languageEnglish
Pages (from-to)576-580
Number of pages5
JournalBritish Journal of Pharmacology
Volume113
Issue number2
DOIs
Publication statusPublished - Oct 1994
Externally publishedYes

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Aldehyde Reductase
Streptozocin
Blood Vessels
Phenylephrine
Aorta
Carbachol
Nitroprusside
Vasoconstrictor Agents
Colforsin
Vasodilator Agents
ponalrestat

Cite this

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abstract = "The responses of rat isolated aortae to vasoconstrictor and vasodilator agents have been studied in 14‐day streptozotocin‐diabetic rats. The effects of treatment with the aldose reductase inhibitor, ponalrestat, on these responses have also been investigated. Maximum contractile responses and aortic sensitivity to phenylephrine were significantly enhanced in 14‐day diabetic aortae. In contrast, endothelium‐dependent relaxations to carbachol were depressed in diabetic rats, whilst endothelium‐independent relaxations to forskolin and sodium nitroprusside were unchanged. Pretreatment with ponalrestat (25 mg kg−1, daily) prevented both the enhanced maximum contractile responses to phenylephrine and the depressed endothelium‐dependent relaxations to carbachol in aortae from 14‐day diabetic rats. Ponalrestat however, had no effect on the reduced phenylephrine EC50 values observed in tissues from diabetic animals. It is concluded that ponalrestat prevents the depression of endothelium‐dependent aortic relaxations induced by diabetes of 14 days duration, suggesting that the polyol pathway is involved in these vascular changes. Ponalrestat does not prevent the increase in aortic sensitivity to α1adrenoceptor agonists. 1994 British Pharmacological Society",
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AU - Otter, Donna J.

AU - Chess‐Williams, Russell

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N2 - The responses of rat isolated aortae to vasoconstrictor and vasodilator agents have been studied in 14‐day streptozotocin‐diabetic rats. The effects of treatment with the aldose reductase inhibitor, ponalrestat, on these responses have also been investigated. Maximum contractile responses and aortic sensitivity to phenylephrine were significantly enhanced in 14‐day diabetic aortae. In contrast, endothelium‐dependent relaxations to carbachol were depressed in diabetic rats, whilst endothelium‐independent relaxations to forskolin and sodium nitroprusside were unchanged. Pretreatment with ponalrestat (25 mg kg−1, daily) prevented both the enhanced maximum contractile responses to phenylephrine and the depressed endothelium‐dependent relaxations to carbachol in aortae from 14‐day diabetic rats. Ponalrestat however, had no effect on the reduced phenylephrine EC50 values observed in tissues from diabetic animals. It is concluded that ponalrestat prevents the depression of endothelium‐dependent aortic relaxations induced by diabetes of 14 days duration, suggesting that the polyol pathway is involved in these vascular changes. Ponalrestat does not prevent the increase in aortic sensitivity to α1adrenoceptor agonists. 1994 British Pharmacological Society

AB - The responses of rat isolated aortae to vasoconstrictor and vasodilator agents have been studied in 14‐day streptozotocin‐diabetic rats. The effects of treatment with the aldose reductase inhibitor, ponalrestat, on these responses have also been investigated. Maximum contractile responses and aortic sensitivity to phenylephrine were significantly enhanced in 14‐day diabetic aortae. In contrast, endothelium‐dependent relaxations to carbachol were depressed in diabetic rats, whilst endothelium‐independent relaxations to forskolin and sodium nitroprusside were unchanged. Pretreatment with ponalrestat (25 mg kg−1, daily) prevented both the enhanced maximum contractile responses to phenylephrine and the depressed endothelium‐dependent relaxations to carbachol in aortae from 14‐day diabetic rats. Ponalrestat however, had no effect on the reduced phenylephrine EC50 values observed in tissues from diabetic animals. It is concluded that ponalrestat prevents the depression of endothelium‐dependent aortic relaxations induced by diabetes of 14 days duration, suggesting that the polyol pathway is involved in these vascular changes. Ponalrestat does not prevent the increase in aortic sensitivity to α1adrenoceptor agonists. 1994 British Pharmacological Society

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