Aldose reductase inhibitors zopolrestat and ferulic acid alleviate hypertension associated with diabetes: effect on vascular reactivity
- 1 February 2013
- journal article
- Published by Canadian Science Publishing in Canadian Journal of Physiology and Pharmacology
- Vol. 91 (2), 101-107
- https://doi.org/10.1139/cjpp-2012-0232
Abstract
This study investigated the effect of aldose reductase (AR) inhibitors on hypertension in diabetes. Diabetes was induced with streptozotocin, while AR inhibitors zopolrestat and ferulic acid were administered at 2 weeks after streptozotocin treatment and for 6 weeks afterwards. Then, blood pressure (BP) and serum level of glucose were determined. Concentration–response curves for phenylephrine (PE), KCl, and acetylcholine (ACh) were obtained in isolated aorta. In addition, ACh-induced NO and reactive oxygen species (ROS) generation in aorta and histopathology were examined. Compared with the control animals, diabetes increased diastolic and systolic BP. AR inhibitors reduced diastolic BP elevation without affecting the developed hyperglycaemia. Diabetes increased the contractile response of aorta to KCl, and decreased the relaxation response to Ach, while administering AR inhibitors prevented an impaired response to ACh. Incubation of aorta isolated from diabetic animals with AR inhibitors did not affect the impaired relaxation response to ACh. In addition, AR inhibitors negated the impaired Ach-stimulated NO generation seen in aorta isolated from diabetic animals. Furthermore, diabetes was accompanied with marked infiltration of leukocytes in aortic adventitia, endothelial cell pyknosis, and increased ROS formation. AR inhibitors reduced leukocyte infiltration and inhibited endothelial pyknosis and ROS formation. In conclusion, AR inhibitors negate diabetes-evoked hypertension via ameliorating impaired endothelial relaxation and NO production.Keywords
This publication has 32 references indexed in Scilit:
- Arginase inhibition alleviates hypertension associated with diabetes: Effect on endothelial dependent relaxation and NO productionVascular Pharmacology, 2012
- Rosiglitazone, a peroxisome proliferator-activated receptor γ stimulant, abrogates diabetes-evoked hypertension by rectifying abnormalities in vascular reactivityClinical and Experimental Pharmacology and Physiology, 2012
- Nitric oxide synthases: regulation and functionEuropean Heart Journal, 2011
- Pentoxifylline alleviates vascular impairment in insulin resistance via TNF-α inhibitionNaunyn-Schmiedebergs Archiv für experimentelle Pathologie und Pharmakologie, 2011
- Haem oxygenase‐1 induction protects against tumour necrosis factor α impairment of endothelial‐dependent relaxation in rat isolated pulmonary arteryBritish Journal of Pharmacology, 2009
- Ferulic acid provides neuroprotection against oxidative stress-related apoptosis after cerebral ischemia/reperfusion injury by inhibiting ICAM-1 mRNA expression in ratsBrain Research, 2008
- Superoxide production and LDL oxidation by diabetic neutrophilsJournal of Diabetes and its Complications, 1996
- Inhibitory Effect of Ferulic Acid and Isoferulic Acid on Murine Interleukin-8 Production in Response to Influenza Virus Infectionsin vitroandin vivoPlanta Medica, 1995
- Pharmacokinetics of the Aldose Reductase Inhibitor, Zopolrestat, in HumansThe Journal of Clinical Pharmacology, 1994
- Direct measurement of polyol pathway activity in the ocular lensDiabetes, 1984