A novel complex of arginine-silicate improves micro- and macrovascular function and inhibits glomerular sclerosis in insulin-resistant JCR:LA-cp rats.
OBJECTIVE
The metabolic syndrome, with associated vasculopathy, is a major cause of cardiovascular disease and nephropathy. Impaired nitric oxide (NO) metabolism and endothelial function is an important component of the disease process. Increasing the availability of arginine, the precursor of NO, might enhance vascular function and protect against end-stage disease.


METHODS
Insulin-resistant JCR:LA-cp rats were treated with arginine-silicate-inositol complex or arginine-HCl at 1.0 g kg(-1) day(-1) (expressed as arginine-HCl) from 8 to 13 weeks of age. The contractile/relaxant function of thoracic aortae and coronary arteries was assessed in vitro. Kidneys were assessed for severity of glomerular sclerosis.


RESULTS
Arginine-silicate complex, but not arginine-HCl, normalised the hypercontractile response of the aorta to phenylephrine via an NO-dependent pathway. Coronary artery function, as indicated by reactive hyperaemia to warm ischaemia, was enhanced by both arginine compounds. In addition, the arginine-silicate complex increased coronary vasodilatation in response to bradykinin. Glomerular sclerosis was significantly reduced in rats treated with the arginine-silicate complex.


CONCLUSIONS
Treatment with exogenous arginine, in an efficiently absorbed form, improves vascular function and reduces nephropathy in an animal model of insulin resistance and cardiovascular disease, via mechanism(s) independent of insulin concentration. Enhancement of NO metabolism through increased availability of the precursor arginine appears to offer protection against micro- and macrovascular disease associated with the metabolic syndrome and insulin resistance.
Proctor
S D
SD
Metabolic and Cardiovascular Diseases Laboratory, Department of Agricultural, Food and Nutritional Science, 4-10 Agriculture Forestry Centre, University of Alberta, Edmonton, Alberta, Canada.
Kelly
S E
SE
Russell
J C
JC
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D001120:Arginine / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D001775:Blood Circulation / Q000187:drug effects / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D002149:Energy Intake; D006321:Heart / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D009765:Obesity / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D017640:Silicates / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D017640:Silicates; D009599:Nitroprusside; D001120:Arginine; D000109:Acetylcholine