Desmopressin-induced release of Tissue-Type Plasminogen Activator (t-PA) in human forearm is not influenced by nitric oxide synthesis inhibition

We recently demonstrated that desmopressin (DDAVP), in addition to vasodilation, induces a massive local release of t-PA from the forearm vascular bed. The mechanisms behind these responses are not fully understood. In the present study, we investigated the effect of nitric oxide synthesis inhibition on forearm blood flow (FBF) and t-PA release during DDAVP stimulation. Methods: Six young, healthy, normotensive, non-smoking males participated. Catheters were placed in the brachial artery and a deep antecubital vein of the non-dominant arm. After baseline registrations, either placebo (saline) or NGmonomethyl-L-arginine (L-NMMA) was infused in the brachial artery at a rate of 4 μmol/min. After 5 minutes, DDAVP (70 ng/min) was co-infused for 15 minutes. With an interval of at least 1 hour, the procedure was repeated with the other substance (L-NMMA/saline). Blood samples were simultaneously collected from artery and vein before, during and after infusions. Forearm blood flow (FBF) was measured by plethysmography and interconverted to plasma flow by means of arterial hematocrits. t-PA antigen was determined in duplicate by ELIS A. Net release of t-PA at each time point was defined as the product of the venoarterial concentration gradient and local plasma flow. Results: At baseline, there was a significant t-PA release of 5-10 ng per min and L tissue that was not affected by LNMMA alone. DDAVP stimulated a 10-fold increase in tPA release rates during both L-NMMA and placebo infusions (ANOVA, p=0.001 and 0.0001, respectively), tPA release peaked at the end of infusions and slowly declined thereafter. L-NMMA suppressed basal FBF by 30% (P=0.07), but had no effect on the moderate (2-fold) FBF increment during DDAVP. Conclusions: Nitric oxide synthesis inhibition does not influence basal or DDAVP-stimulated t-PA release from the forearm vascular bed. Although similar intracellular transduction pathways are involved in the release of t-PA and nitric oxide, there is no obligate coupling between these compounds. It remains to be elucidated, if vasodilation and t-PA release are mediated via the same mechanisms following V2 receptor stimulation.