Release of tissue-type plasminogen activator in response to muscarinic receptor stimulation in human forearm

We have recently shown that mental stress increases local net release of tissue-type plasminogen activator (t-PA) across the forearm vascular bed. However, the mechanisms responsible for the t-PA release in man during stress are undefined. To study the effects of endothelial cell receptor stimulation and fluid shear stress we used the perfused forearm model to characterize the in vivo tissue plasminogen activator (t-PA) response in man to methacholine (Mch) and sodium nitroprusside (SNP), at doses calculated to cause similar degrees of vasodilation. The study was performed in 7 healthy young men (age 22-24 yrs) without hypertension, diabetes mellitus, or hypercholesterolemia. Each subject received double-blind step-wise i. a. infusions of Mch (0.1-0.8-4.0 micrograms/min) and SNP (0.5-2.5-10 micrograms/min) in randomized order. Each dose step was infused for 5 min. Forearm blood flow was assessed by plethysmography. Net release/uptake was expressed as the product of arterio-venous concentration gradient and forearm plasma flow. At pre-infusion baseline, there was a significant net release of t-PA antigen of approximately 0.9 ng x min-1 x 100 ml-1 and t-PA activity of 3.5 fmol x min-1 x 100 ml-1 across the forearm. I.a. infusion of Mch and SNP increased forearm blood flow from 1.9 to 14.9 and from 1.8 to 12.1 ml x min-1 x 100 ml-1, respectively (Mch vs SBP N.S.).(ABSTRACT TRUNCATED AT 250 WORDS)