Valsartan improves resting skin blood flow in type 2 diabetic patients and reduces poly(adenosine diphosphate-ribose) polymerase activation.
OBJECTIVE
To examine the effect of a 12-week daily treatment with 160 mg of valsartan, an angiotensin II receptor blocker, on the microcirculation and macrocirculation of type 2 diabetic patients (T2DM) and healthy subjects.


METHODS
This was a prospective, randomized, double-blind, placebo-controlled crossover study. Thirteen T2DM with no severe complications and 13 healthy subjects completed the trial.


RESULTS
Treatment with valsartan in T2DM improved the resting forearm skin blood flow and increased the resting brachial artery diameter but had no effects on arterial blood pressure, large vessel vascular reactivity, or carotid intima-media thickness. Resting skin blood flow increased by 60% (2%-90%; median and 25th-75th percentiles) during valsartan treatment and by only 2% (-22% to 27%) during placebo treatment (P < .05). No changes were observed in the nondiabetic subjects. Immunostaining studies of forearm skin biopsy samples from T2DM and healthy subjects showed that valsartan reduced poly(adenosine diphosphate-ribose) polymerase (PARP) activity in 50% (6/12) of the subjects. PARP activity remained unchanged in placebo-treated subjects (P < .02). In addition, valsartan treatment increased CD31 staining in 33% (4/12) of the subjects, whereas no change was noted in sequential skin biopsy samples of placebo-treated subjects (P = .057). Valsartan had no effect on the biochemical markers of endothelial cell activation and other cytokines, including CAMs, interleukin 6, tumor necrosis factor alpha, C-reactive protein, adiponectin, and plasma activator inhibitor 1.


CONCLUSIONS
Valsartan increases the resting skin blood flow in T2DM, likely through reduction of PARP activity.
Shrikhande
Gautam
G
Immunobiology Research Center and Division of Vascular Surgery, Harvard Medical School, Boston, Massachusetts.
Khaodhiar
Lalita
L
Scali
Salvatore
S
Lima
Christina
C
Hubbard
Matthew
M
Dudley
Katherine
K
Ganda
Om
O
Ferran
Christiane
C
Veves
Aristidis
A
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001707:Biopsy, Needle; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D011336:Probability; D011446:Prospective Studies; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D018570:Risk Assessment; D012720:Severity of Illness Index; D012867:Skin / Q000098:blood supply* / Q000473:pathology; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine