Tissue Plasminogen Activator in Essential Hypertension

Abstract

Tissue plasminogen activator (t-PA) is regarded as the major activator of fibrinolysis. It is synthetised and stored in endothelial cells, from where it is released into the blood stream. Although several stimuli for t-PA release have been described such as exercise [1], venous occlusion [2] and cardiopulmonary bypass [3], the effect of blood pressure alterations on endothelial t-PA secretion re mains to be clarified. It has been attempted to correlate blood fibrinolytic activity with arterial blood pressure in a number of studies [4][5][6][7][8], but no clear-cut conclusions could be attained. Based on these considerations, the pre sent study was designed in order to compare the basal plasma t-PA levels in hypertensive and normotensive sub jects and to determine the effect of acute blood pressure reduction by sublingual nifedipine on plasma t-PA levels in essential hypertension.The study group included 18 previously untreated patients with diastolic blood pressure 105 mm Hg or higher, mean age 46 ± 2 years and 13 healthy age-and sex-matched normotensive patients. Blood samples were drawn without stasis, by means of an indwelling cathe ter placed in the antecubital fossa 30 min prior to test. The patency of the needle was maintained by slow saline infusion. Upon the comple tion of a 30-min period of recumbent rest, the baseline samples were drawn at 9:00 a.m. in both groups. Immediately after the baseline sampling, the hypertensive patients were given 10 mg nifedipine sub lingually. Additional samples were drawn 15,30 and 60 min after nife dipine. All subjects remained in the supine position during the study. Blood pressure measurements were performed at 0,15,30 and 60 min just after sampling. T-PA antigen levels were measured by the sand wich ELISA technique [9], The significance of the difference was analysed by the MannWhitney U and Wilcoxon rank tests for intergroup and intragroup measurements, respectively. The values were expressed as mean ± standard error of mean. Fig. 1. The effect of sublingual nifedipine on blood pressure and plasma t-PA antigen level in hypertensive patients (n = 18). Figure 1 shows the changes in mean systolic and dia stolic blood pressure and t-PA antigen levels after the ad ministration of sublingual nifedipine. The mean systolic and diastolic blood pressure in the hypertensive group at 0 min were 174.2 ± 6.0 mm Hg and 118.1 ± 2.8 mm Hg, respec tively. Gradual lowering of systolic and diastolic blood pressure was observed during the study period; minimal blood pressure values (systolic 155.0 ± 6.3 mm Hg, diastolic 103.6 ±3.2 mm Hg) were reached at 60 min (p <0.001).The mean baseline (0 min) t-PA antigen level of hyper tensive patients was 7.9 ± 1.6 ng/ml, which was not found to be significantly different from the mean t-PA antigen level