Angiotensin II does not affect endothelial tone in Type 1 diabetes-results of a double-blind placebo controlled trial.
OBJECTIVE
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.


CONCLUSIONS
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.
Browne
D L
DL
Academic Department of Diabetes and Endocrinology, Queen Alexandra Hospital, Portsmouth, UK. dbrowne@doctors.org.uk
Meeking
D R
DR
Allard
S E
SE
Munday
J L
JL
Shaw
K M
KM
Cummings
M H
MH
D000109:Acetylcholine / Q000008:administration & dosage; D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D001713:Biphenyl Compounds / Q000008:administration & dosage; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage; D007261:Infusions, Intra-Arterial; D000077405:Irbesartan; D008297:Male; D009599:Nitroprusside / Q000008:administration & dosage; D012039:Regional Blood Flow / Q000187:drug effects; D013777:Tetrazoles / Q000008:administration & dosage; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage; D019323:omega-N-Methylarginine / Q000008:administration & dosage
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D013777:Tetrazoles; D014665:Vasodilator Agents; D000804:Angiotensin II; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D000077405:Irbesartan; D000109:Acetylcholine; D007213:Indomethacin