In vitro and in vivo effects of tPA and PAI-1 on blood vessel tone.

Tissue type plasminogen activator (tPA) is a key enzyme in the fibrinolytic cascade. In this paper we report that tPA contains 2 independent epitopes that exert opposite effects on blood vessel tone. Low concentrations of tPA (1 nM) inhibit the phenylephrine (PE)-induced contraction of isolated aorta rings.

Human alpha-defensin regulates smooth muscle cell contraction: a role for low-density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor.

We have previously identified alpha-defensin in association with medial smooth muscle cells (SMCs) in human coronary arteries. In the present paper we report that alpha-defensin, at concentrations below those found in pathological conditions, inhibits phenylephrine (PE)-induced contraction of rat aortic rings. Addition of 1 microM alpha-defensin increased the half-maximal effective concentration (EC(50)) of PE on denuded aortic rings from 32 to 630 nM.

Effects of the SOD mimic nitroxide 3-carbamoyl-PROXYL on oxidative stress markers and endothelial dysfunction in streptozotocin-induced diabetic rats.

Objective: To evaluate the effects of 3-carbamoyl-PROXYL (CP), a stable superoxide dismutase (SOD) mimic compound, on oxidative stress markers and endothelial dysfunction in diabetic rats.

Animals And Methods: Rats were made diabetic by a single vein injection of streptozotocin (65 mg/kg) and diabetes was verified by the existence of excessive hyperglycemia a week after the treatment. Control and diabetic rats received vehicle or drug for eight weeks, after which the vascular tissue was examined for relaxation and oxidative stress markers.

Binding of urokinase to low density lipoprotein-related receptor (LRP) regulates vascular smooth muscle cell contraction.

Urokinase plasminogen activator (uPA) is a multifunctional protein that has been implicated in several physiological and pathological processes involving cell adhesion and migration in addition to fibrinolysis. In a previous study we found that two-chain urokinase plasminogen activator (tcuPA) stimulates phenylephrine-induced vasoconstriction of isolated rat aortic rings. In the present paper we report that uPA(-/-) mice have a significantly lower mean arterial blood pressure than do wild type mice and that aortic rings from uPA(-/-) mice show an attenuated contractile response to phenylephrine.

Effects of the superoxide dismutase-mimetic compound tempol on endothelial dysfunction in streptozotocin-induced diabetic rats.

Evidence exists to support the beneficial effects of superoxide dismutase on endothelial dysfunction induced by hyperglycemia in vitro. In vivo, however, studies of the effects of native superoxide dismutase preparations on the vascular complications accompanying diabetes are limited, and their therapeutic application potential has so far been disappointing. The objective of this study was to evaluate, for the first time in vivo, the effects of long-term administration of tempol, a stable superoxide dismutase-mimic compound, on diabetes-induced endothelial dysfunction in rats.