Blockade of sensory abnormalities and kinin B(1) receptor expression by N-acetyl-L-cysteine and ramipril in a rat model of insulin resistance.
Glucose-fed rat is a model of insulin resistance that displays sensory polyneuropathy and hypertension. This study aimed at comparing the beneficial effects of N-acetyl-L-cysteine (NAC, antioxidant) and ramipril (angiotensin-1 converting enzyme inhibitor) on tactile and cold allodynia induced by chronic glucose feeding. Impact of these treatments was also assessed on hypertension, plasma glucose and insulin concentrations, insulin resistance and kinin B(1) receptor expression. Male Wistar rats (50-75 g) were given 10% d-glucose in their drinking water for 11 weeks or tap water (controls). Glucose-fed rats were treated either with NAC (1 g/kg/day, gavage), ramipril (1 mg/kg/day in drinking water) or no drug during the last 5 weeks. Glucose feeding for 6 weeks induced a significant increase in systolic blood pressure and hyperglycaemia which was accompanied by tactile and cold allodynia. At 11 weeks, plasma insulin, insulin resistance (HOMA index), kinin B(1) receptor mRNA in spinal cord and renal cortex and B(1) receptor binding sites in spinal cord were enhanced in glucose-fed rats. NAC and ramipril caused a progressive to complete inhibition of tactile and cold allodynia from 6 to 11 weeks. High systolic blood pressure, hyperinsulinemia, insulin resistance and kinin B(1) receptor expression were also normalized or attenuated in glucose-fed rats by either treatment. Results suggest that chronic treatment with an antioxidant or an ACE inhibitor provides similar beneficial effects on sensory polyneuropathy, hypertension and insulin resistance in glucose-fed rats. Both therapies were associated with a reduction of the expression of the pro-nociceptive kinin B(1) receptor.
Department of Physiology, Faculty of Medicine, Université de Montréal, Succursale Centre-Ville, Montréal, Québec, Canada.
Mahmoud Ali
MA
Ismael
Sébastien
S
Talbot
Cynthia L
CL
Carbonneau
Christian M
CM
Beauséjour
Réjean
R
Couture
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003553:Cystine / Q000031:analogs & derivatives* / Q000494:pharmacology; D048909:Diabetes Complications / Q000139:chemically induced / Q000178:diet therapy* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005947:Glucose; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010147:Pain Measurement; D012333:RNA, Messenger / Q000378:metabolism; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1 / Q000235:genetics / Q000378:metabolism*; D012677:Sensation / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D000975:Antioxidants; D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D003553:Cystine; D005947:Glucose; D017257:Ramipril; C030905:N-monoacetylcystine