Nitric oxide may be required to prevent hypertension at the onset of diabetes.
Nitric oxide (NO) plays an important role in the regulation of vascular tone, and evidence suggests that endothelial-dependent relaxation, possibly mediated via NO, is impaired in diabetes. However, the role of the endothelium in arterial pressure control early in diabetes, before dysfunction develops, is not known. This was evaluated in the present study by comparing the responses to induction of diabetes in vehicle-treated rats (D, n = 7) vs. rats chronically treated with N(G)-nitro-L-arginine methyl ester (L-NAME; D+L, n = 8). A nondiabetic group also was treated with L-NAME (L, n = 7) to control for L-NAME effects over time, independent of diabetes. After baseline measurements, rats were given either vehicle or L-NAME (10 microg. kg(-1). min(-1) iv) infusion throughout the experiment. Six days later, streptozotocin (60 mg/kg iv) was administered, followed by a 3-wk diabetic study period. Induction of diabetes in the D+L rats caused a marked and progressive increase in mean arterial pressure throughout the diabetic period, averaging approximately 70 mmHg greater than in the D rats and approximately 20 mmHg greater than in the L rats. Glomerular filtration rate and renal plasma flow tended to increase during diabetes, but this trend was reversed in the D+L rats. In addition, plasma renin activity increased in the D and D+L rats during week 1 of diabetes but then returned to control in the D rats, while continuing to increase in the D+L rats. These results suggest that, in the early stages of diabetes, NO synthesis is important to prevent hypertension from developing, possibly through actions to maintain glomerular filtration and suppress renin secretion.
Fitzgerald
S M
SM
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA. sfitzgerald@physiology.umsmed.edu
Brands
M W
MW
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism* / Q000517:prevention & control; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine; D012982:Sodium, Dietary / Q000378:metabolism
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007328:Insulin; D012982:Sodium, Dietary; D009569:Nitric Oxide; D012964:Sodium; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester