Selective reversal of hyperglycemia-evoked gastric myoelectric dysrhythmias by nitrergic stimulation in healthy humans.
Acute hyperglycemia disrupts gastric myoelectric rhythm in healthy humans. Defective nitrergic function is a factor in animal models of diabetic gastropathy. We tested participation of nitrergic pathways in hyperglycemia-evoked myoelectric dysrhythmias and compared their role in preventing dysrhythmic actions of experimental motion sickness. Twelve healthy volunteers underwent electrogastrography (EGG) with and without intravenous 20% dextrose to produce plasma glucoses of 250 mg/dl. EGG continued for 2 h after oral nitroglycerin (9 mg) or the cyclic GMP-specific phosphodiesterase inhibitor sildenafil (100 mg). In separate studies, 12 volunteers underwent circular vection (60 degrees /s) without and 90 min after nitroglycerin (9 mg) or sildenafil (100 mg) with concurrent EGG. Hyperglycemia decreased recording time in normal rhythm, increased tachygastria more than 3-fold, and decreased power of the dominant frequency (P < 0.05). Nitroglycerin and sildenafil reversed effects of hyperglycemia, improving normal rhythm, decreasing tachygastria (both P < 0.05), and blunting power decreases. Neither agent affected EGG rhythm during euglycemia. Vection decreased time in normal rhythm and increased tachygastria (P < 0.05). However, nitroglycerin and sildenafil did not reverse dysrhythmic effects of vection (P = N.S.). In conclusion, administration of a nitric oxide (NO) donor or an inhibitor of cyclic GMP-selective phosphodiesterase reverses the dysrhythmic effects of hyperglycemia on gastric myoelectric activity in healthy humans. These agents have no effect on dysrhythmias during motion sickness. These findings are consistent with selective impairment of nitrergic function in this model of diabetic gastropathy and suggest that NO donors and other agents that increase NO activity may be useful for treating diabetic dysrhythmias.
Coleski
Radoslav
R
Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
Gonlachanvit
Sutep
S
Owyang
Chung
C
Hasler
William L
WL
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003250:Constriction; D005260:Female; D005769:Gastrointestinal Motility; D006801:Humans; D006943:Hyperglycemia / Q000097:blood*; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology; D010063:Ovum / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones
D001786:Blood Glucose; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D005996:Nitroglycerin