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OBJECTIVE: An effect of insulin that is crucial for stimulating glucose uptake is its ability to increase the number of perfused capillaries, and thereby enhance its own delivery, and that of glucose, to muscle cells. To unravel possible mechanisms involved in the insulin-sensitizing effects of angiotensin II receptor blockers (ARBs) in hypertensive individuals we investigated the effect of single-dose ARB administration on insulin-mediated microvascular perfusion in hypertensive individuals. METHODS: We examined the effects of ARB administration on hyperinsulinemia-associated capillary density by measuring baseline skin capillary density, capillary density during reactive hyperemia (hyperemic capillary recruitment), and capillary density during venous congestion in 17 hypertensive individuals in the basal state, during a hyperinsulinemic euglycemic clamp, and during a hyperinsulinemic clamp with acute ARB administration (600mg irbesartan), acute calcium channel blockade (CCB; 10mg felodipine ER), as a control for the reduction in blood pressure, or placebo. In addition, insulin sensitivity and blood pressure were measured. RESULTS: Compared to the basal state, hyperinsulinemia increased baseline capillary density (57.3+/-6.8 vs. 60.3+/-7.9n/mm(2), P<0.01), but not hyperemic capillary recruitment. ARB and CCB treatment induced similar blood pressure reductions. Compared to placebo, ARB, but not CCB, increased hyperinsulinemia-associated baseline capillary density (+2.3+/-3.4 (P=0.02) and -0.4+/-4.4n/mm(2), respectively). Hyperinsulinemia-associated hyperemic capillary recruitment was not altered by either treatment. Compared to placebo, neither ARB nor CCB treatment enhanced insulin sensitivity. CONCLUSIONS: Acute ARB administration increases insulin-induced microvascular perfusion in mildly hypertensive individuals; this beneficial effect on microvascular perfusion was however not associated with increased insulin-mediated glucose uptake.