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1 Department of Pharmacology and Human Physiology, University of Bari, Bari, Italy
2 Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
3 Diabetes Unit, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, Maryland, United States
4 NCCAM, NIH, Bethesda,, Maryland, United States; Diabetes Unit, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, Maryland, United States
* To whom correspondence should be addressed. E-mail: monica{at}farmacol.uniba.it.
Epigallocatechin gallate (EGCG), a bioactive polyphenol in green tea, may augment metabolic and vascular actions of insulin. We investigated effects of EGCG treatment to simultaneously improve cardiovascular and metabolic function in SHR rats (model of metabolic syndrome with hypertension, insulin resistance, and overweight). In acute studies, EGCG (1 - 100 µM) elicited dose-dependent vasodilation in mesenteric vascular beds (MVB) from SHR ex vivo, inhibitable by L-NAME (NOS antagonist) or wortmannin (PI 3-kinase inhibitor). In chronic studies, 9-wk old SHR were treated by gavage for 3 weeks with EGCG (200 mg/kg/d), enalapril (30 mg/kg/d), or vehicle. A separate group of SHR receiving L-NAME (80 mg/L in drinking water) was treated for 3 weeks with either EGCG or vehicle. Vasodilator actions of insulin were significantly improved in MVB from EGCG- or enalapril-treated SHR (compared with vehicle-SHR). Both EGCG and enalapril therapy significantly lowered systolic blood pressure (SBP) in SHR. EGCG therapy of SHR significantly reduced infarct size and improved cardiac function in Langendorff-perfused hearts exposed to ischemia/reperfusion injury (I/R). In SHR given L-NAME, effects of EGCG on SBP and I/R were not observed. Both enalapril and EGCG treatment of SHR improved insulin sensitivity and raised plasma adiponectin. We conclude that acute actions of EGCG to stimulate production of NO from endothelium using PI 3-kinase dependent pathways may explain, in part, beneficial effects of EGCG therapy to simultaneously improve metabolic and cardiovascular pathophysiology in SHR. These findings may be relevant to understanding potential benefits of green tea consumption in patients with metabolic syndrome.
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