Effects of cyclo-oxygenase inhibition on vasodilatory response to acetylcholine in patients with type 1 diabetes and nondiabetic subjects.
OBJECTIVE
Studies examining vasodilatory responses to acetylcholine (ACh) and its derivatives have been conflicting. Enhanced activation of the cyclo-oxygenase pathway and increased availability of vasodilatory prostanoids may occur in type 1 diabetes, and this may compensate for the observed reduction in nitric oxide (NO) activity We examined the role of cyclo-oxygenase inhibition on vasodilatory responses in 12 healthy normotensive type 1 diabetic adults and 12 nondiabetic control subjects of similar age, sex, and BMI.


METHODS
Forearm blood flow was measured using a venous occlusion plethysmography technique at baseline and after brachial artery infusions of ACh (7.5, 15, and 30 microg/min). Forearm blood flow at baseline and after ACh was then reexamined after local intra-arterial infusion of indomethacin (0.3 mg/100 ml forearm volume), a cyclo-oxygenase inhibitor.


RESULTS
Baseline blood flow in the diabetic and control groups were similar (2.65 +/- 0.26 vs. 2.59 +/- 0.20 ml/min per 100 ml, respectively; P = 0.4). After indomethacin infusion, the vasodilatory responses to all doses of ACh were reduced in both the diabetic (by 25.30 +/- 4.90%) and control group (by 11.23 +/- 5.45%). However, the reduction in blood flow response to ACh after indomethacin was greater in diabetic patients compared with control subjects (P = 0.03).


CONCLUSIONS
Our findings suggest that vasodilatory, prostanoids are important in determining endothelial response to ACh in diabetic and nondiabetic subjects. Increased prostaglandin-mediated vasodilation may compensate for attenuated responses to NO previously reported in diabetic subjects. These findings may partly explain the conflicting reports of endothelial dysfunction in patients with type 1 diabetes.
Meeking
D R
DR
Department of Diabetes and Endocrinology, Queen Alexandra Hospital, Cosham, Portsmouth, UK. dmeeking@aol.com
Browne
D L
DL
Allard
S
S
Munday
J
J
Chowienczyck
P J
PJ
Shaw
K M
KM
Cummings
M H
MH
D000109:Acetylcholine / Q000494:pharmacology*; D000328:Adult; D001783:Blood Flow Velocity; D015992:Body Mass Index; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D014664:Vasodilation / Q000187:drug effects*
D016861:Cyclooxygenase Inhibitors; D000109:Acetylcholine; D007213:Indomethacin