L-NAME- Induced Hypertension in the WKY and BHR Rat

Abstract

The development of hypertension in normotensive Wistar-Kyoto (WKY) and borderline hypertensive rats (BHR) was studied by inhibiting the synthesis of nitric oxide, an endothelial-derived relaxing factor. The BHR is genetically predisposed to developing hypertension in response to chronic exposure to environmental stress. After normalizing for initial systolic blood pressure (SBP), rats received drinking water that contained N-nitro-L-arginine methyl ester (L-NAME) at concentrations of 0, 75, and 150 mg/L for three to four weeks. SBP, heart rate (HR), body weight (BW), and water consumption were measured weekly throughout L-NAME administration as well as during the subsequent two to three weeks following L-NAME withdrawal. L-NAME at either concentration produced progressively increasing hypertension in both the WKY and BHR rats by 21 days. The L-NAME-induced increase in SBP was reversed in the WKY when L-NAME was withdrawn but not in the BHR. Oral administration of L-NAME had no consistent effect on HR, BW, or water consumption although the administration of the 150 mg/L concentration was in some instances fatal to BHRs. The irreversibility of the L-NAME-induced hypertension in the BHR illustrates the significance of genetic predisposition to the development of sustained hypertension. This method for induction of sustained hypertension in rats (BHR), which can be compared with normotensive litter mates, provides a useful hypertensive model.