title: Impaired capacity for stimulated fibrinolysis in primary hypertension is restored by antihypertensive therapy.
abstract: The increased risk for myocardial infarction and ischemic stroke in primary hypertension suggests that the condition is associated with prothrombotic mechanisms. We have shown that patients with hypertension have an impaired capacity for acute endothelial tissue-type plasminogen activator (t-PA) release, an important local protective response to prevent formation of intravascular thrombi. The aim of the present study was to investigate whether this impairment could be restored by the lowering of blood pressure. The capacity for acute t-PA release in response to intraarterial infusion of substance P at 8 pmol/min was investigated in a perfused-forearm study in 20 hypertensive patients (12 men and 8 women). Studies were performed when patients were untreated and after 8 weeks of randomized treatment with lisinopril or felodipine that lowered blood pressure by 26/10 and 24/12 mm Hg, respectively. The t-PA release response increased significantly with treatment (ANOVA, P=0.0001), with a similar effect in the 2 treatment groups. The peak release of t-PA increased from 257 (58) to 445 (77) ng/min x L/tissue(-1) (t test, P=0.02). Also, treatment shortened the average time to peak secretion from 6.7 (1.4) to 2.7 (0.3) min (t test, P=0.01). In 6 patients with a delayed secretory peak (9 minutes or later), treatment normalized the response (chi2 test, P=0.008). Antihypertensive therapy restores the capacity for acute t-PA release and improves the rapidity of the response in patients with primary hypertension. Similar responses with the 2 regimens suggest that the improvement is related to the blood pressure reduction as such. This effect may contribute to the thromboprotective effect of antihypertensive treatment.
authors.affiliation: Clinical Experimental Research Laboratory, Sahlgrenska University Hospital/Ostra, Institute of Medicine, Göteborg University, Göteborg, Sweden.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Ridderstråle
authors.forename: Erik
authors.initials: E
authors.lastname: Ulfhammer
authors.forename: Sverker
authors.initials: S
authors.lastname: Jern
authors.forename: Thórdís
authors.initials: T
authors.lastname: Hrafnkelsdóttir
mesh_terms: D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D015736:Felodipine / Q000627:therapeutic use*; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D005542:Forearm / Q000098:blood supply; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D007269:Injections, Intra-Arterial; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow / Q000187:drug effects; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D013373:Substance P; D017706:Lisinopril; D010959:Tissue Plasminogen Activator; D015736:Felodipine