Chronic low-dose L-NAME treatment effect on cardiovascular system of borderline hypertensive rats: feedback regulation?

OBJECTIVES: The effect of 8-week-lasting low-dose treatment of NG-Nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, was investigated in borderline hypertensive rats (BHR) to examine, whether dose of 1.5 mg/kg/day affects feedback regulation of NO synthesis.

METHODS: Blood pressure (BP) of 12 weeks old Wistar and BHR rats was determined non-invasively by tail-cuff. NO synthase (NOS) activity was determined by conversion of [3H]-L-arginine to [3H]-L-citrulline in the aorta, left ventricle (LV) and hypothalamus. Vascular function of the femoral artery was determined using Mulvany's myograph in isometric conditions.

RESULTS: Chronic low-dose L-NAME treatment of BHR induced sustained blood pressure elevation and left ventricular hypertrophy associated with the decrease in NOS activity in left ventricle and unaltered NOS activity in the aorta. By contrast, the improvement of LV and aortic NOS activity was found in Wistar rats. In hypothalamus, no changes in NOS activity were found in both BHR and Wistar. In Wistar, acetylcholine-induced relaxation of the femoral artery was increased and serotonin-induced and noradrenalin-induced constriction were reduced in L-NAME treated group. These effects, however, were not seen in BHR.

CONCLUSION: The results indicate that NOS/NO feedback regulation works differently under conditions of normotension and prehypertension. Low-dose L-NAME treatment accentuated NO production in normotensive rats, but it failed to improve NOS activity in BHR.