Effect of β-adrenergic and renin-angiotensin system blockade on myocyte apoptosis and oxidative stress in diabetic hypertensive rats

Fabio Fiordaliso, Noeleen De Angelis, Antonio Bai, Ivan Cuccovillo, Monica Salio, Domenico Maria Serra, Roberto Bianchi, Roberta Razzetti, Roberto Latini, Serge Masson

Research output: Contribution to journalArticle

Abstract

Diabetes aggravates the clinical severity and represents an additional independent risk factor of hypertension. Since both diseases separately concur to cardiomyocyte apoptosis, a mechanism at least partly involving unbalanced oxidative stress, we investigated whether the combination of diabetes and hypertension potentiated cardiac cell death in experimental models, compared to either disease alone. We also evaluated the short-term effects of different drugs in these models. Streptozotocin-induced diabetic normotensive (WKY) or hypertensive (SHR) rats were treated for one week with a DA22 agonist (CHF-1024), a selective β1 adrenergic blocker (metoprolol), an angiotensin II-receptor blocker (valsartan) or a radical scavenger (tempol). In separate experiments, isolated cardiomyocytes were cultured in high glucose medium (25 mM) containing the same drugs. Although the number of apoptotic cardiomyocytes and the myocardial density of oxygen radicals were higher in non diabetic hypertensive than in normotensive controls, diabetes raised these variables to comparable absolute levels in both strains. All drugs except metoprolol significantly reduced apoptosis and oxidative stress in the diabetic animals of both strains and in the isolated myocytes cultured with high glucose. In conclusion, hypertensive rat is no more susceptible than its normotensive control to acute apoptosis induced by diabetes. Oxidative stress might be considered the common trigger for cardiac myocyte apoptosis in both conditions.

Original languageEnglish
Pages (from-to)951-959
Number of pages9
JournalLife Sciences
Volume81
Issue number12
DOIs
Publication statusPublished - Sep 1 2007

Keywords

  • β-adrenergic system
  • Apoptosis
  • Diabetes
  • Hypertension
  • Oxidative stress
  • Renin-angiotensin system

ASJC Scopus subject areas

  • Pharmacology

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