Impaired endothelial release of tissue-type plasminogen activator in patients with chronic kidney disease and hypertension.
We have shown that the capacity for local release of tissue-type plasminogen activator (tPA) from the vascular endothelium is impaired in patients with primary hypertension. Because this response is an important protective mechanism against intravascular clotting, we investigated whether this system is also defective in patients with advanced chronic kidney disease and hypertension. Nine nondiabetic nonsmoking men with chronic kidney disease (glomerular filtration rate 11 to 28 mL/min x 1.73 m2; aged 33 to 75 years) were compared with age-matched healthy controls. Intraarterial infusions of desmopressin, methacholine, and sodium nitroprusside were given locally in the brachial artery. Forearm blood flow was measured by venous occlusion plethysmography and blood collected repeatedly during the desmopressin infusion for determination of stimulated net and total cumulated release of tPA. The maximal release rate of active tPA (P<0.05) and the capacity for acute tPA release were markedly impaired in the renal patients as compared with healthy subjects (ANOVA, P=0.013). Accordingly, the accumulated release of tPA was 1905 (SEM 366) and 3387 (718) ng/L tissue, respectively (P<0.05). However, there were no significant differences in vasodilator responses between the groups. Thus, patients with advanced chronic kidney disease and hypertension have a markedly impaired capacity for acute release of tissue plasminogen activator, despite preserved endothelium-dependent vasodilation. This defect may contribute to a defective local defense against arterial thrombosis.
Hrafnkelsdóttir
Thórdís
T
Clinical Experimental Research Laboratory, Sahlgrenska University Hospital/Ostra, SE 41685 Göteborg, Sweden. thordis.hrafnkelsdottir@hjl.gu.se
Ottosson
Pia
P
Gudnason
Thorarinn
T
Samuelsson
Ola
O
Jern
Sverker
S
D000328:Adult; D000368:Aged; D001916:Brachial Artery; D003894:Deamino Arginine Vasopressin; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D006978:Hypertension, Renovascular / Q000150:complications / Q000503:physiopathology; D007261:Infusions, Intra-Arterial; D007674:Kidney Diseases / Q000150:complications / Q000503:physiopathology*; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D009599:Nitroprusside; D010991:Plethysmography; D012636:Secretory Rate / Q000187:drug effects; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects
D016210:Methacholine Chloride; D009599:Nitroprusside; D010959:Tissue Plasminogen Activator; D003894:Deamino Arginine Vasopressin