MECHANISMS FOR THE ACTION OF VASOACTIVE SUBSTANCES AND GROWTH FACTORS.

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In the present study, the mechanisms for the action of vasoactive substances and growth factors were investigated, using simultaneous measurements of intracellular calcium concentration ([Ca^<2+>]i) and tension of the various vascular tissues and vascular endothelial cells. To further explore the mechanisms, we also employed the measurements of mRNA level of some kind of receptors. The major findings were as follows.1.Mechanisms for the vasorelaxants(1)We found the isoproterenol and papavrine decreases not only [Ca^<2+>]i but also Ca^<2+> sensitivity of the myofilaments.(2)Nicorandil was found to decrease Ca^<2+> sensitivity as well as [Ca^<2+>]i2.Mechanisms for the contraction induced by agonists(1)The endothelin-1 (ET-1) and ET-3 induced contraction of the porcine coronary artery were found to be different.(2)The mechanisms for the ethanol-induced contraction of the coronary artery were found to involve the activation of G-protein.(3)The difference of the norepinephrine-and serotonin-induced contraction of the rabbit femoral artery were investigated.(4)The effects of angiotensin II (Ang II) and cAMP on the expression of Ang II receptor mRNA were investigated.3.Investigation of the vascular endothelial cells(1)We found that ET-1 induced the increase in [Ca^<2+>]i partially through pertussis toxin sensitive G-protein.(2)Motilin was found to induce Ca^<2+> transients of the vascular endothelial cells.(3)The sequence of the pig ET_A receptor were determined.4.Investigation of the growth factor.We found that platelet derived growth factor progresses the cell cycle without the rise in [Ca^<2+>]i of the rat aortic smooth muscle cells in primary culture.5.Investigation of the tracheal smooth muscle cells.Lidocaine, a local anesthesia, was found to relax tracheal smooth muscle by reducing the Ca^<2+> sensitivity of the myofilaments.