Inhibition of nitric oxide synthesis potentiates hypertension during chronic glucose infusion in rats.
Endothelial dysfunction has been proposed to contribute to impaired blood flow control or hypertension in many conditions characterized by hyperinsulinemia or hyperglycemia. However, most studies have focused on whether endothelial dysfunction is present in the established phases of these various hypertensive states, and there is little known concerning the role of the endothelium in the initial stages. This study tested whether nitric oxide production, before endothelial dysfunction develops, plays an important role in counteracting the hypertensive response to chronic glucose infusion. Glucose was infused (18.6 mg/kg per minute IV) for 7 days in 8 normal rats (G) and in 9 rats with a long-term background intravenous infusion of N(G)-nitro-L-arginine methyl ester (L-NAME) at 10 microg/kg per minute (G+L). Mean arterial pressure (MAP), measured 24 hours per day, increased an average of approximately 11 mm Hg in the G rats. L-NAME treatment increased MAP an average 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 increased from an average of 389+/-8 bpm to 441+/-16 bpm by day 6, whereas there was no significant change in the G rats. Glomerular filtration rate decreased 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 results show that NO is required to minimize the increase in MAP during glucose infusion and suggest that renal and neural mechanisms may be important in mediating that effect.
Claxton
C R
CR
University of Mississippi Medical Center, State University, Jackson, MS 39216, USA.
Brands
M W
MW
Fitzgerald
S M
SM
Cameron
J A
JA
D000818:Animals; D001786:Blood Glucose; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000201:enzymology*; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007328:Insulin; D019001:Nitric Oxide Synthase; D012083:Renin; D005947:Glucose; D019331:NG-Nitroarginine Methyl Ester