Angiotensin II type 1 receptor blockade improves hyperglycemia-induced endothelial dysfunction and reduces proinflammatory cytokine release from leukocytes
Journal of Cardiovascular Pharmacology , Volume 49 - Issue 1 p. 6- 12
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.
|Angiotensin receptor blockade, Diabetes mellitus, Endothelial function, Hyperglycemia, Hyperglycemic clamp, Leucocyte|
|Journal of Cardiovascular Pharmacology|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
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