Acute angiotensin II receptor blockade improves insulin-induced microvascular function in hypertensive individuals

ObjectiveAn 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.MethodsWe 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 (600 mg irbesartan), acute calcium channel blockade (CCB; 10 mg felodipine ER), as a control for the reduction in blood pressure, or placebo. In addition, insulin sensitivity and blood pressure were measured.ResultsCompared to the basal state, hyperinsulinemia increased baseline capillary density (57.3 ± 6.8 vs. 60.3 ± 7.9 n/mm2, 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 ± 4.4 n/mm2, respectively). Hyperinsulinemia-associated hyperemic capillary recruitment was not altered by either treatment. Compared to placebo, neither ARB nor CCB treatment enhanced insulin sensitivity.ConclusionsAcute 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.

The effect of single-dose ARB administration on hyperinsulinemia-induced capillary density in hypertensive individuals. ⁎P = 0.02 for the increase with ARB.Figure optionsDownload as PowerPoint slideHighlights
► Angiotensin II AT1 receptor blockade (ARB) improves insulin sensitivity in hypertensive individuals.
► In addition to its metabolic actions, insulin promotes its own access to muscle cells by recruiting capillaries; an effect crucial for stimulating glucose uptake.
► Using nailfold capillaroscopy, we demonstrated that administration of a single dose of ARB increases hyperinsulinemia-associated microvascular perfusion in hypertensive individuals.