Insulin resistance due to chronic salt restriction is corrected by alpha and beta blockade and by L-arginine

Dietary salt restriction is associated with evidence of low insulin sensitivity. The current study was undertaken to investigate whether sympathetic nervous system and l-arginine-nitric oxide pathway activities are linked to insulin resistance in rats under chronic low salt intake. Male Wistar rats were fed a low (LSD) or normal (NSD) salt diet from weaning to adulthood. A euglycemic hyperinsulinemic clamp was performed in 4 sub-groups on each diet: (1) sympathetic nervous system blockade (propranolol and prazosin), (2) vehicle, (3) L-arginine, and (4) D-arginine. Blood pressure, heart rate and metabolic measurements were done before and 45 min after drug infusion and at the end of the clamp. At baseline conditions, body weight, hematocrit, blood glucose, plasma insulin, cholesterol, and triacylglycerols were higher in LSD than in NSD rats. Systolic blood pressure was lower and heart rate was higher in rats on LSD than on NSD. Glucose uptake was lower on LSD compared to NSD. Sympathetic nervous system blockade and L-arginine did, and vehicle and D-arginine did not improve glucose uptake in LSD rats. On NSD there was no effect of any of the infused drugs. A positive correlation between plasma nitrate and nitrite at the end of clamp and glucose uptake was observed in L-arginine--but not in D-arginine-infused LSD rats. These results provide evidence that the sympathetic nervous system and the L-arginine-nitric oxide pathway are involved in the glucose uptake impairment induced by chronic dietary salt restriction.