Acetylcholine-mediated vasodilatation and tissue-type plasminogen activator release in normal and hypertensive men.
Muscarinic agents release tissue plasminogen activator (t-PA) in the forearm circulation of normal subjects, but no information exists about their effect in those hypertensive patients in whom the response to endothelial-mediated vasodilators is blunted. Acetylcholine, an endothelium-dependent vasodilator and a muscarinic agonist that releases t-PA from in-vitro systems, and sodium nitroprusside, an endothelium-independent vasodilator, were infused into the brachial artery at rates calculated to cause a similar degree of vasodilatation. The study was performed in five elderly, smoking hypertensive patients in whom the clustering of detrimental factors for endothelial function permitted prediction of defective endothelial-mediated vasorelaxation, and five young, normotensive, nonsmoking male volunteers. Forearm blood flow was assessed by venous plethysmography; t-PA and plasminogen activator inhibitor 1 (PAI-1) antigen values were expressed as flow-dependent (net release, the product of venoarterial concentration gradient and forearm blood flow) or independent (absolute and fractional concentration gradients) indices. In patients, acetylcholine did not change flow and net release and concentration gradients of t-PA, suggesting that vasodilatation as such, possibly by increasing fluid shear stress, may induce t-PA release in human forearm. In normal subjects, acetylcholine and sodium nitroprusside increased t-PA antigen net release at the highest infusion rate, an effect attributable to forearm hyperperfusion, since absolute and fractional gradients did not change significantly. PAI-1 antigen did not change during either infusion in both controls and patients, indicating the absence of an endothelial pool to be mobilized acutely.
Dell'Omo
G
G
Dipartimento di Cardiologia, Angiologia e Pneumonologia, Università di Pisa, Italy.
Ferrini
L
L
Morale
M
M
De Negri
F
F
Melillo
E
E
Carmassi
F
F
Pedrinelli
R
R
D000109:Acetylcholine / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D005542:Forearm / Q000098:blood supply / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood* / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D017395:Plasminogen Activator Inhibitor 1; D014665:Vasodilator Agents; D009599:Nitroprusside; D010959:Tissue Plasminogen Activator; D000109:Acetylcholine