Nitric oxide synthase (NOS) activity and abolishment of endothelium dependent relaxation

Endothelial dysfunction occurs in post-ischemic tissues and is characterized by a marked reduction in. endothelium dependent relaxation (EDR). Detergent treatment has been used to create a model of impaired endothelial reactivity, however, it is not known if this effect requires total loss of NOS or simply impaired signal transduction. This study evaluated the correlation between the abolishment of EDR and NOS activity. Isolated rat hearts were perfused according to the Langendorff technique at constant flow with a modified Krebs Henseleit solution and the effects of histamin (\0 M) were evaluated. Subsequently hearts were bolused with approximately 1.2cc Triton-X 100 (1:400) and then retested for histamine vasodilatory response. These hearts were then assayed for NOS activity using the L-[14C]-arginine to L-[uC]-citrulline conversion method. All hearts initially exhibited reduction of coronary pressure upon infusion of histamine (16±4mmHg) which was totally abolished after treatment with Triton. NOS activity measurements of Triton-treated hearts revealed no significant change when compared to the control group (0.91±0.07 vs 0.82±0.01 pmoles/min x mg prot; p=NS). Therefore, abolishment of EDR can occur in the presence of active NOS and is probably due to an interruption of the signal transduction pathway.