| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1986: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1985: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
The endothelium has been known to play an important role in controlling vascular tone in physiological and pathological conditions. Isolated porcine coronary artery preconstricted with prostaglandin <F_2> (PG <F_2> ) relaxed by substance P in a dose-dependent manner. The relaxation was dependent on the presence of endothelium and was significantly inhibited when more than 50% of endothelium covered over the intimal surface was intentionally rubbed. Among blood components such as platelets, leucocytes, fibrin-fibrinogen products and other formed elements, includinig erythrocytes, hemolysate (HE), in particular oxyhemoglobin (Hb) strongly potentiated myogenic tone of canine cerebral artery, which also seems to be in part dependent on the endothelium. The static and dynamic stretch of isolated cerebral artery in form of helical or ring segment, i.e., excessive elongation of the preparation up to increase in basal tension of 1.5 g and quick stretch at a rate of 10 cm/sec, respectively, or
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sudden increase in the intraluminal perfusion pressure (IPP) of cylindrical segment of the artery from 60 to 100 cm <H_2> O produced contraction. A small amount of HE (20-60 mg/dl as Hb) obtained from autologous blood, inducing a slight increase in basal tension potentiated not only the stretch- or IPP-induced contraction but also vasoconstrictions produced by serotonin, histamine, norepinephrine and PG <F_(2X)> 2-3 times those of control. The contraction potentiated by HE was inhibited by Ca antagonists of nifedipine-verapamil type and withdrawal of wxtracellular Ca. HE did not produce any apparent increase in tension of muscle bundle of the cerebral artery which was chemically skinned by saponin and preloaded with Ca. Furthermore, the contraction potentiated by HE was inhibited by removal of endothelium, while the reduced contraction was partially restored when the endothelium-removed preparation was in contact with intimal surface of the endothelium-unrubbed one. Simultaneous and continuous recordings of contractions and Ca transients by use of intracellular Ca analyzer in the cerebral artery produced by several agonistic stimuli, high K and oxyhemoglobin indicated that the increase in contraction in response to these stimuli was concomitant with augmentation of ca transients. These results suggest that a small amount of HE acts as a Ca-dependent potentiator of various vasoconstrictor stimuli and that the effect is dependent on endothelium. In the study, endothelium acts dilative in porcine coronary artery, but constrictive in canine cerebral artery. It seems possible that the endothelium liberates vasodilative or constrictive substance(s), depending on the agonistic stimuli and vascular tissues used. Vascular heterogeneity implies that not only medial smooth muscles and their surrounding tissues such as nervous elements, but also the endothelium may be diverse in the structures and functins for regulation of vascular tone. Less
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