Systemic hypotensive response to protamine following chronic inhibition of nitric oxide synthase in rats

Purpose: The aims of the present studies were to determine whether the systemic hypotensive response to protamine was modified in rats pre-treated for two weeks with the nitric oxide synthase inhibitor, N(G)-nitro-L- arginine-methyl ester (L-NAME); and to evaluate the inhibitory effect of heparin on the systemic hypotensive response to protamine in vivo. Methods: Male rats were randomly assigned into four groups. Normal saline 12 μl · day^-1, D-NAME (an inactive enantiomer of L-NAME), 10 mg · kg^-1day^-1, L-NAME, 1 or 10 mg · kg^-1 · day^-1 ip was administered for two weeks and the haemodynamic changes were measured after protamine administration. In another experiment, male rats were assigned to two groups. In one, the heparin group, protamine was administered after heparin had been administered and in the other, protamine group, protamine alone was administered. Results: L-NAME inhibited the decrease in systemic arterial pressure after protamine administration (P < 0.05), but D-NAME had no effect. Also, heparin reduced the decrease in systemic arterial pressure after protamine (P < 0.05). Conclusion: Nitric oxide is mainly responsible for mediation of the systemic hypotensive response to protamine which is also reduced by heparin.