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Effects of cyclo-oxygenase inhibition on vasodilatory response to acetylcholine in patients with type 1 diabetes and nondiabetic subjects.

  1. D R Meeking,
  2. D L Browne,
  3. S Allard,
  4. J Munday,
  5. P J Chowienczyck,
  6. K M Shaw and
  7. M H Cummings
  1. Department of Diabetes and Endocrinology, Queen Alexandra Hospital, Cosham, Portsmouth, UK. dmeeking@aol.com
    Diabetes Care 2000 Dec; 23(12): 1840-1843. https://doi.org/10.2337/diacare.23.12.1840
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    Abstract

    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. RESEARCH DESIGN AND 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.

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    December 2000, 23(12)
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    Effects of cyclo-oxygenase inhibition on vasodilatory response to acetylcholine in patients with type 1 diabetes and nondiabetic subjects.
    D R Meeking, D L Browne, S Allard, J Munday, P J Chowienczyck, K M Shaw, M H Cummings
    Diabetes Care Dec 2000, 23 (12) 1840-1843; DOI: 10.2337/diacare.23.12.1840

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    Effects of cyclo-oxygenase inhibition on vasodilatory response to acetylcholine in patients with type 1 diabetes and nondiabetic subjects.
    D R Meeking, D L Browne, S Allard, J Munday, P J Chowienczyck, K M Shaw, M H Cummings
    Diabetes Care Dec 2000, 23 (12) 1840-1843; DOI: 10.2337/diacare.23.12.1840
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