Dietary NG-nitro-L-arginine induces sustained hypertension in normotensive Wistar-Kyoto rats.

1. Prolonged oral administration of NG-nitro-L-arginine (L-NNA) for a period of 5 weeks in 8 week old male normotensive Wistar-Kyoto (WKY) rats (n = 10), induced hypertension in all animals. Hypertension was characterized by a sharp initial increase in both systolic blood pressure (SBP) and mean blood pressure (MBP) until the third day (from 126 +/- 3 mmHg to 160 +/- 6 mmHg and from 95 +/- 3 mmHg to 133 +/- 6 mmHg, respectively). This was followed by a gradual and steady increase until the fourth week (163 +/- 4, 171 +/- 3 and 189 +/- 8 mmHg for SBP in weeks 1, 2 and 4, respectively; and 135 +/- 4, 143 +/- 3 and 157 +/- 5 mmHg for MBP in weeks 1, 2 and 4, respectively). 2. Intravenously L-arginine.HCl (500 mg/kg) administered on the last day of the 5th week abolished the effect of dietary L-NNA on the arterial blood pressure. 3. Dietary L-NNA-induced hypertension in WKY rats is easily obtainable and free of any surgical operation, and can be utilized as a new experimental model to further understand the importance of endothelium-dependent relaxing factor/nitric oxide in blood pressure regulation and to clarify the pathological significance in intact animals where endothelium-dependent relaxing factor/nitric oxide is functionally involved.