Inhibition of nitric oxide synthesis potentiates hypertension during chromic glucose infusion in rats

Endothelial dysfunction has been proposed to contribute to impaired blood f low control or hypertension in many conditions characterized by hyperinsuli nemia or hyperglycemia. However, most studies have focused on whether endot helial dysfunction is present in the established phases of these various hy pertensive states, and there is little known concerning the role of the end othelium in the initial stages. This study tested whether nitric oxide prod uction, before endothelial dysfunction develops, plays an important role in counteracting the hypertensive response to chronic glucose infusion. Gluco se was infused (18.6 mg/kg per minute IV) for 7 days in 8 normal rats (G) a nd in 9 rats with a long-term background intravenous infusion of N-G-nitro- L-arginine methyl ester (L-NAME) at 10 mu g/kg per minute (G + L). Mean art erial pressure (MAP), measured 24 hours per day, increased an average of ap proximate to 11 mm Hg in the G rats. L-NAME treatment increased MAP an aver age of 28+/-2 mm Hg in the G+L rats, and glucose infusion raised MAP >30 mm Hg above that, averaging 155+/-8 mm Hg by day 6. In addition, heart rate i ncreased from an average of 389+/-8 bpm to 441+/-16 bpm by day 6, whereas t here was no significant change in the G rats. Glomerular filtration rate de creased significantly with L-NAME treatment and decreased in both groups by day 3 of glucose infusion, reaching lower levels in the G+L rats. These re sults show that NO is required to minimize the increase in MBP during gluco se infusion and suggest that renal and neural mechanisms may be important i n mediating that effect.