Role of heme oxygenase in modulating endothelial function in mesenteric small resistance arteries of spontaneously hypertensive rats

Enzo Porteri, Luigi F. Rodella, Rita Rezzani, Damiano Rizzoni, Silvia Paiardi, Carolina De Ciuceis, G. E M Boari, Eleonora Foglio, Gaia Favero, Nicola Rizzardi, Caterina Platto, Enrico Agabiti Rosei

Research output: Contribution to journalArticlepeer-review

Abstract

It has been proposed that endothelial dysfunction is due to the excessive degradation of nitric oxide (NO) by oxidative stress. The enzyme heme-oxygenase (HO) seems to exert a protective effect on oxidative stress in the vasculature, both in animal models and in humans. The objective of this study is to evaluate the effects of inhibition or activation of HO on endothelial function in mesenteric small resistance arteries of spontaneously hypertensive rats (SHR). Six SHR were treated with cobalt protoporphyrin IX 50 mgKg (CoPP), an activator of HO; six SHR with stannous mesoporphyrin 30 mgKg (SnMP), an inhibitor of HO, and six SHR with saline. As controls, six Wistar-Kyoto rats (WKY) were treated with CoPP, six WKY with SnMP, and six WKY with saline. Drugs were injected in the peritoneum once a week for 2 weeks. Systolic blood pressure (SBP) was measured (tail cuff method) before and after treatment. Mesenteric small resistance arteries were mounted on a micromyograph. Endothelial function was evaluated as a cumulative concentration-response curve to acetylcholine (ACH), before and after preincubation with N(G)-methyl-L-arginine (L-NMMA, inhibitor of NO synthase), and to bradykinin (BK). In SHR treatment with CoPP, improved ACH-and BK-induced vasodilatation (ANOVA p <0.001) and this improvement was abolished by L-NMMA (ANOVA p <0.001). SnMP was devoid of effects on endothelial function. In WKY, both activation and inhibition of HO did not substantially affect endothelium-mediated vasodilatation. The stimulation of HO seems to induce an improvement of endothelial dysfunction in SHR by possibly reducing oxidative stress and increasing NO availability.

Original languageEnglish
Pages (from-to)560-571
Number of pages12
JournalClinical and Experimental Hypertension
Volume31
Issue number7
DOIs
Publication statusPublished - Nov 2009

Keywords

  • Carbon monoxide
  • Endothelial function and dysfunction
  • Heme oxygenase
  • Hypertension
  • Nitric oxide
  • Small arteries
  • Vessels

ASJC Scopus subject areas

  • Physiology
  • Internal Medicine

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