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Heme oxygenase-1 induction protects against hypertension associated with diabetes: effect on exaggerated vascular contractility

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Abstract

Disturbances in vascular reactivity are important components of diabetes-evoked hypertension. Heme oxygenase-1 (HO-1) is a homeostatic enzyme upregulated in stress. This study aims to investigate the protective effect of HO-1 against diabetes-evoked hypertension. Rats were left 8 weeks after diabetes induction with streptozotocin to induce vascular dysfunction in the diabetic groups. HO-1 inducers, hemin and curcumin, were daily administrated in the last 6 weeks in the treated groups after 2 weeks of induction. Then, at the end of the study (8 weeks), HO-1 protein level was assessed by immunofluorescence; blood pressure (BP) was recorded; isolated aorta reactivity to phenylephrine (PE) and KCl was studied; reactive oxygen species (ROS) generation was determined; and serum level of glucose, advanced glycation end products (AGEs), and tumor necrosis factor alpha (TNF-α) were determined. While not affected by diabetes, HO-1 protein expression was strongly induced by hemin or curcumin administration. Compared with control animals, diabetes increased systolic and pulse BP. Induction of HO-1 by hemin or curcumin significantly reduced elevated systolic BP and abolished elevated pulse BP without affecting the developed hyperglycemia or AGEs level. The possibility that alterations in vascular reactivity contributed to diabetes–HO-1 BP interaction was investigated. Diabetes increased contractile response of the aorta to PE and KCl, while HO-1 induction by curcumin or hemin prevented aorta-exaggerated response to PE and KCl. Furthermore, the competitive HO inhibitor, tin protoporphyrin, abolished the protective effect of hemin. Diabetes was accompanied with elevated level of TNF-α and ROS generation, while HO-1 induction abrogated increased TNF-α and ROS generation. Collectively, induction of HO-1 protects against hypertension associated with diabetes via ameliorating exaggerated vascular contractility by reducing TNF-α and aortic ROS levels.

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Abbreviations

ANOVA:

Analysis of variance

eNOS:

Endothelial nitric oxide synthase

HO-1:

Heme oxygenase-1

NO:

Nitric oxide

PE:

Phenylephrine

ROS:

Reactive oxygen species

SnPP:

Tin protoporphyrin

STZ:

Streptozotocin

TNF-α:

Tumor necrosis factor alpha

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt

    N. Hassan, H. M. El-Bassossy & M. N. M. Zakaria

  2. Department of Pharmacology, Faculty of Pharmacy, King Abdulaziz University, P.O. Box 80260, Jeddah, 21589, Kingdom of Saudi Arabia

    H. M. El-Bassossy

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  1. N. Hassan
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  2. H. M. El-Bassossy
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  3. M. N. M. Zakaria
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Correspondence to H. M. El-Bassossy.

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Hassan, N., El-Bassossy, H.M. & Zakaria, M.N.M. Heme oxygenase-1 induction protects against hypertension associated with diabetes: effect on exaggerated vascular contractility. Naunyn-Schmiedeberg's Arch Pharmacol 386, 217–226 (2013). https://doi.org/10.1007/s00210-012-0822-3

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