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Plasminogen activator activity (PAA), t-PA antigen level, plasminogen activator inhibition (PAI) and plasmin inhibition (PI) showed a circadian variation in rat aorta, heart, brain, and lungs of both sexes, but in a different way depending on the organ and the fibrinolytic parameter studied and the sex as well. In general, the lowest values of PAA and t-PA antigen were found in the early morning and the highest values in late afternoon, while PAI or PI showed the opposite pattern (with the exception of lungs). In kidneys and liver the fibrinolytic parameters studied showed no circadian variation. Sex-related differences, mostly quantitative, were noted in aorta, heart, brain and kidneys, with lower PAA and t-PA antigen and higher PAI or PI in the male than in the female.

Unilateral or bilateral ovariectomy was performed in young and adult rats. Mainly bilateral ovariectomy induced variable changes of plasminogen activator activity (PAA), plasminogen activator inhibition (PAI) and plasmin inhibition (PI) in key organs (brain, lungs, heart, aorta and kidneys). The most remarkable changes were induced after bilateral ovariectomy performed in young animals and mostly after two and three months of ovariectomy. Therefore, the effect of ovariectomy on tissue PAA, PAI or PI was variable and dependent on the extent of the ovariectomy (unilateral or bilateral), the age of the animal at ovariectomy (young or adult), the time after ovariectomy, and the organ. An additional interesting finding was the dissociation in the response of tissue anti-t-PA and anti-u-PA activities to ovariectomy in some of the organs studied.

Chronic hypertension was induced in rats after partial nephrectomy. The systolic blood pressure was significantly elevated from the first week after nephrectomy to the end of the experimentation (8th week). Plasminogen activator activity (PAA) and plasminogen activator inhibition (PAI) showed a tissue- and time-dependent pattern of changes in some key organs compared to controls (sham-operated rats). Two weeks after nephrectomy (one week after the induction of hypertension) the PAA was markedly increased in lungs, heart and aorta. In aorta the PAA continued to be enhanced until the end of the experimentation (the 8th week after nephrectomy), while in heart and lungs the PAA returned to the normal eight weeks after nephrectomy. In vena cava, brain and liver no change in PAA was noticed compared to controls. Tissue PAI was mostly increased or unchanged, while tissue plasmin inhibition (PI) was unchanged. The differential response of PAA and PAI was varying not only from one organ to another or in the same organ at a given time but also in the same organ throughout experimentation. In a number of nephrectomized rats, however, hypertension was not induced. In these rats similar changes in tissue PAA and PAI were noted compared to hypertensive nephrectomized rats. Therefore, all the changes in the parameters studied should be due to the partial nephrectomy itself. In conclusion, experimentally induced chronic hypertension had not any effect on tissue PAA, PAI and PI.

The effect of endotoxin, aspirin and endotoxin after administration of aspirin on the tissue plasminogen activator activity (PAA), plasminogen activator inhibition (PAI) and plasmin inhibition (PI) was studied in the rat. PAA, PAI and PI were determined in key organs (brain, heart, lungs, kidneys, liver and aorta) spectrophotometrically by procedures involving hydrolysis of the chromogenic substrate S-2251. Aspirin at three different doses had not any significant effect on tissue PAA; PAI and PI were affected in several organs. Four hours after a sustained infusion of endotoxin PAA was found to be increased in brain, kidneys and aorta, decreased in heart and lungs, while in liver the PAA was unchanged compared to controls. Changes in PAI and PI showed also a tissue variation. In endotoxin-infused rats pretreated with aspirin the PAA changes induced by endotoxin were prevented or modified; PAI and PI were affected in most organs studied. However, this effect of aspirin was varying and depending on the tissue, the parameter studied and the dose of aspirin. In some organs, as the heart and lungs, changes in PAI or PI were noticed, while neither aspirin nor endotoxin separately induced such changes in these organs. Also, a differential response of PAI and PI to the same stimulus in the same tissue was a noteworthy finding. The results of the present study show that the response of PAA, PAI and PI to aspirin depends on the tissue, the physiological or pathophysiological condition of the tissue and the dose of the aspirin.