Nitric oxide synthase inhibition in lean and obesehypertensive dogs

The aim of this study was to determine whether nitric oxide (NO) activity is abnormal in the obese hypertensive dog. Differences in cardiovascular and renal response to NO inhibition were investigated in six lean and six obese-hypertensive dogs. Arterial pressure response to the NO inhibitor nitro-L-arginine (LNA; 3,5,6,7,8,9,10mg/kg; Q20min), was examined following ganglionic blockade. Maximal MAP response to LNA was similar in the lean (180.9±7.7mmHg) and obese (205.2±17.3mmHg). However, the cumulative dose to maximal response was greater in the obese (obese, 173.2± 6.4mg/kg LBM; lean, 59.7ig.5mg/kg LBM; p=0.017), despite similar lean body mass. Renal function was studied following tOOmg of LNA and reversal with 150mg/kg L-arginine. PAH clearance (CPAH) decreased significantly following LNA administration in both the lean (p=0.049) and obese (p=0.038) dogs. The magnitude of change in C_PAH, urine sodium excretion ( U_NaV) and GFR following LNA was not different between groups. The average urine production (UPROD) in lean dogs was significantly higher than the obese (p=0.04). A significant decrease in UPROD occurred in the lean group following LNA (p=0.01). UPROD decreased in the obese dogs, but not significantly. LNA reduced average urine sodium excretion (U_NaV) of all dogs significantly (p=0.003), with no difference observed between the groups. In summary, the blood pressure response to NO inhibition is similar in lean and obese dogs, but higher LNA doses are required to reach maximal response in the obese. Nitric oxide inhibition reduces U_NaV and£_PAH similarly in lean and obese, with little effect on GFR. These studies suggest that cardiovascular and renal responses to NO synthase inhibition may be altered in obesity. Supported by DK44446.