Angiotensin II does not affect endothelial tone in Type 1 diabetes-results of a double-blind placebo controlled trial
| Autor: | Darryl Meeking, J. Munday, Duncan L. Browne, Ken Shaw, S. E. Allard, Michael H. Cummings |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Nitroprusside medicine.medical_specialty Endothelium Vasodilator Agents Endocrinology Diabetes and Metabolism Indomethacin Tetrazoles Prostaglandin Vasodilation Nitric oxide chemistry.chemical_compound Endocrinology Irbesartan Double-Blind Method Internal medicine Diabetes mellitus Internal Medicine medicine Humans Infusions Intra-Arterial Cyclooxygenase Inhibitors Enzyme Inhibitors omega-N-Methylarginine Dose-Response Relationship Drug business.industry Angiotensin II Biphenyl Compounds medicine.disease Acetylcholine Forearm Diabetes Mellitus Type 1 medicine.anatomical_structure chemistry Regional Blood Flow Vasoconstriction Female Endothelium Vascular business Angiotensin II Type 1 Receptor Blockers medicine.drug Blood vessel |
| Zdroj: | Diabetic Medicine. 23:53-59 |
| ISSN: | 1464-5491 0742-3071 |
| DOI: | 10.1111/j.1464-5491.2005.01727.x |
| Popis: | Aims Previously, we have demonstrated that patients with normoalbuminuric Type 1 diabetes are characterized by impaired nitric oxide bioavailability compensated for by increased vasodilatory prostanoid-mediated vasodilation. Experimental evidence suggests vascular responses to endogenous angiotensin II involve the nitric oxide and prostaglandin pathways. We examined whether selective blockade of angiotensin II influences endothelial tone with particular reference to the nitric oxide/prostaglandin pathways in patients with Type 1 diabetes free from vascular complications. Methods At baseline, we studied changes in forearm blood flow in response to brachial arterial infusions of acetylcholine, l-NMMA, a combination of l-NMMA and the cyclo-oxygenase inhibitor indomethacin and nitroprusside in 30 patients with normoalbuminuric Type 1 diabetes [21 male, 9 female; age 38.5 ± 1.9 years (mean ± sem)]. Patients were randomized to 2 weeks’ treatment with placebo or the selective angiotensin II receptor blocking agent irbesartan, 300 mg, prior to forearm vasoactive responses being re-examined. Results The forearm responses to nitroprusside and acetylcholine were unchanged by both placebo (P = 0.23 and P = 0.36, respectively) and irbesartan (P = 0.41 and P = 0.36). Similarily, dose–response curves to acetylcholine in the presense of l-NMMA alone (P = 0.42) and a combination of l-NMMA and indomethacin (P = 0.44) were not altered by angiotensin II blockade. Conclusion This study demonstrated that physiological blockade of endogenous angiotensin II in Type 1 diabetes does not augment agonist-evoked vasodilation or the contribution of nitric oxides and prostanoids to endothelial tone. |
| Databáze: | OpenAIRE |
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