Angiotensin II type 1 receptor blockade improves hyperglycemia-induced endothelial dysfunction and reduces proinflammatory cytokine release from leukocytes
Angiotensin II and glucose share components of their intracellular redox signaling pathways in endothelial and inflammatory cells. We hypothesized that valsartan, an angiotensin II blocker, attenuates hyperglycemia-induced endothelial dysfunction and downregulates release of proinflammatory cytokines from leukocytes. A sustained hyperglycemic clamp (12 mmol/L) to induce endothelial dysfunction was performed in healthy volunteers before and after 4 weeks of treatment with 160 mg of valsartan. Brachial artery flow-mediated vasodilation (FMD), lipopolysaccharide-induced release of interleukin-6 and TNF-α from peripheral blood leukocytes ex vivo, and circulating proinflammatory cytokines were determined before and during the clamp. The hyperglycemic clamp induced a decrease in FMD from 9.2 ± 0.8 (t = 0 hr) to 4.4± 0.5 (t = 2 hr), 3.8 ± 0.5 (t = 4 hr), and 4.8 ± 0.5% (t = 22 hr) during the clamp. Valsartan attenuated endothelial dysfunction [FMD 7.0 ± 0.7 (t = 2 hr), 6.1 ± 0.7 (t = 4 hr), 6.2 ± 0.6% (t = 22 hr); P < 0.005] and decreased the release of interleukin-6 and TNF-α from leukocytes both before and during the clamp (P < 0.05). Valsartan improves hyperglycemia-induced endothelial dysfunction and reduces the cytokine response to an inflammatory stimulus. A pathophysiological link between the effects of hyperglycemia and the renin-angiotensin system on endothelium and peripheral blood leukocytes may underlie the beneficial effects of inhibitors of the renin-angiotensin system on cardiovascular outcome in patients with diabetes mellitus.
|Keywords||Angiotensin receptor blockade, Diabetes mellitus, Endothelial function, Hyperglycemia, Hyperglycemic clamp, Leucocyte|
|Persistent URL||dx.doi.org/10.1097/FJC.0b013e31802b31a7, hdl.handle.net/1765/35866|
Willemsen, J.M., Westerink, J.W., Dallinga-Thie, G.M., van Zonneveld, A.J., Gaillard, C.A., Rabelink, T.J., & de Koning, E.J.. (2007). Angiotensin II type 1 receptor blockade improves hyperglycemia-induced endothelial dysfunction and reduces proinflammatory cytokine release from leukocytes. Journal of Cardiovascular Pharmacology, 49(1), 6–12. doi:10.1097/FJC.0b013e31802b31a7