title: Acute angiotensin II receptor blockade improves insulin-induced microvascular function in hypertensive individuals.
abstract: 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 (600 mg 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 ± 7.9 n/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.
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Centre and Cardiovascular Research Institute Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. a.jonk@maastrichtuniversity.nl
authors.forename: Amy M
authors.initials: AM
authors.lastname: Jonk
authors.forename: Alfons J
authors.initials: AJ
authors.lastname: Houben
authors.forename: Nicolaas C
authors.initials: NC
authors.lastname: Schaper
authors.forename: Peter W
authors.initials: PW
authors.lastname: de Leeuw
authors.forename: Erik H
authors.initials: EH
authors.lastname: Serné
authors.forename: Yvo M
authors.initials: YM
authors.lastname: Smulders
authors.forename: Coen D
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004311:Double-Blind Method; D015736:Felodipine / Q000494:pharmacology; D005260:Female; D015309:Glucose Clamp Technique; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D006946:Hyperinsulinism / Q000097:blood / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology; D000077405:Irbesartan; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D055806:Microvessels / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008875:Middle Aged; D009262:Nails / Q000098:blood supply; D012881:Skin Temperature / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D001786:Blood Glucose; D002121:Calcium Channel Blockers; D007328:Insulin; D013777:Tetrazoles; D000077405:Irbesartan; D015736:Felodipine