Hypertensive Response to Chronic NO Synthase Inhibition is Different in Sprague-Dawley Rats from Two Suppliers
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Experiments were conducted to determine whether Sprague-Dawley rats from different suppliers have the same hypertensive response to chronic inhibition of nitric oxide synthase. Rats (240-260 g) obtained from either Harlan or Charles River Laboratories were maintained in metabolic cages for baseline (week 0) measurements before receiving Nomega-nitro-L-arginine methyl ester (L-NAME) in the drinking water for 2 wk at 5 or 65 mg . kg-1 . day-1. Baseline values for tail cuff pressure (TCP) were significantly higher in Harlan rats (131 +/- 2 mmHg) compared with Charles River rats (108 +/- 3 mmHg, P < 0.001). At 65 mg . kg-1 . day-1, L-NAME produced a significantly larger increase in TCP in Harlan versus Charles River rats (41 +/- 4 vs. 29 +/- 4%, respectively, P < 0.01). Food and water intake and sodium and water excretion were not different between groups. Urinary excretion of nitrate and nitrite (UNOxV) was significantly reduced in all rats given L-NAME. UNOxV was decreased by 69 +/- 12 and 62 +/- 7% in Harlan and Charles River rats, respectively. The lower dose of L-NAME increased TCP and decreased UNOxV in both Harlan and Charles River rats; these effects were more pronounced in the Harlan rats. These results suggest that NO plays a more significant role in the maintenance of arterial pressure in Sprague-Dawley rats from Harlan compared with Charles River Laboratories. Such findings may also provide insight as to why some of the mechanisms associated with chronic L-NAME treatment are not consistent between laboratories.
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