title: Candesartan acutely recruits skeletal and cardiac muscle microvasculature in healthy humans.
abstract: BACKGROUND
  Angiotensin II type 1 receptor (AT(1)R) tone restricts muscle microvascular blood volume (MBV) and decreases muscle insulin delivery and glucose use.
  
  
  OBJECTIVE
  The objective of the study was to examine whether acute AT(1)R blockade alters microvascular perfusion in skeletal and cardiac muscle in humans.
  
  
  METHODS
  The study was conducted at the General Clinical Research Center at the University of Virginia.
  
  
  METHODS
  Eight overnight-fasted healthy young adults were studied thrice in random order. In study 1, each subject received candesartan (32 mg) orally at time 0. In study 2, each subject received placebo at time 0 and a 1 mU/min · kg euglycemic insulin clamp from time 240 to 360 min. In study 3, each subject received candesartan (32 mg) orally at time 0 and insulin infusion from 240 to 360 min. Forearm skeletal and cardiac muscle MBV, microvascular flow velocity, and microvascular blood flow (MBF) were determined at baseline and at 240 and 360 min.
  
  
  RESULTS
  Candesartan treatment acutely recruited microvasculature in both skeletal and cardiac muscle by significantly increasing MBV (P < 0.03 and P = 0.02, respectively) and MBF (P < 0.03 for both) without altering microvascular flow velocity. Insulin infusion significantly increased cardiac MBV (P = 0.02) and MBF (P < 0.02). Superimposing insulin infusion 4 h after candesartan ingestion did not further recruit microvasculature. Insulin-mediated whole-body glucose disposal did not differ with or without candesartan pretreatment.
  
  
  CONCLUSIONS
  Acute AT(1)R blockade with candesartan recruits skeletal as well as cardiac muscle microvasculature in healthy humans without altering insulin-mediated whole-body glucose disposal. This may contribute to the observed improvement in the cardiovascular outcomes in patients receiving prolonged treatment with AT(1)R blockers.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia Health System, P.O. Box 801410, Charlottesville, Virginia 22908, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Sauder
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Linda A
authors.initials: LA
authors.lastname: Jahn
authors.forename: Dale E
authors.initials: DE
authors.lastname: Fowler
authors.forename: Weidong
authors.initials: W
authors.lastname: Chai
authors.forename: Zhenqi
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001713:Biphenyl Compounds; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics; D015309:Glucose Clamp Technique; D006262:Health; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D055806:Microvessels / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007328:Insulin; D013777:Tetrazoles; D005947:Glucose; C081643:candesartan