Reactive hyperemia and tissue-type plasminogen activator release in hypertensive men.
A relationship may exist between endothelial-mediated vasodilation and tissue-type plasminogen activator (t-PA) release. However, the existing evidence is mainly based upon exogenous agonist administration, and needs testing under more physiological conditions. We evaluated the link between t-PA, the key fibrinolytic factor in man, and forearm reactive hyperemia, a model of endogenous endothelial-mediated vasodilation, in 13 uncomplicated hypertensive subjects and six elderly hypertensive patients with atherosclerotic peripheral vascular disease and hypercholesterolemia (i.e a group in whom post-ischemic hyperemia was probably defective because of dysfunctional endothelium). To characterize further the phenomenon, 29 additional uncomplicated hypertensive patients underwent intra-arterial drug infusions. Study variables were forearm blood flow (strain-gauge plethysmography), arterial and venous concentrations of t-PA mass concentrations, and calculated net release (forearm plasma flow x veno-arterial differences). Reactive hyperemia was induced by inflating a cuff midway between systolic and diastolic pressure for 10 min; blood and forearm blood flow were sampled before and after cuff release. Post-ischemic t-PA release increased in uncomplicated hypertensives, and did not change in hypercholesterolemic atherosclerotic patients in whom post-ischemic vasodilation was negligible. Local adenosine (n = 9), acetylcholine (n = 12) and bradykinin (n = 8) vasodilated similarly, but only bradykinin increased t-PA release. Thus, reactive hyperemia stimulates t-PA release, and that relationship is altered when endothelium is dysfunctional. Release of t-PA is independent of forearm vasodilatation, adenosine or biological products of muscarinic stimulation and may, perhaps, be related to the activity of the endogenous kininogen/kinin system.
Dell'Omo
Giulia
G
Dipartimento Cardio Toracico, Università di Pisa, Italy.
De Negri
Ferdinando
F
Carmassi
Franco
F
Ruocco
Lucia
L
Mariani
Mario
M
Pedrinelli
Roberto
R
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006937:Hypercholesterolemia; D006940:Hyperemia / Q000378:metabolism* / Q000503:physiopathology; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D016491:Peripheral Vascular Diseases; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D010959:Tissue Plasminogen Activator; D000241:Adenosine; D000109:Acetylcholine; D001920:Bradykinin