| Co-Investigator(Kenkyū-buntansha) |
TAKEUCHI Kazuhisa School of Medicine, Tohoku University, ., 医学部, 助手 (40260426)
ITO Sadayoshi School of Medicine, Tohoku University, ., 医学部, 講師 (40271613)
OMATA Ken Tohoku Univ.2nd.Dept.Int.Med., assist Prof., 医学部・付属病院, 講師 (50194634)
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| Research Abstract |
Glomerular and tubular functions are important for homeostasis of body fluid and electrolytes, and hence for the regulation of systemic blood pressure. In this project we employed an in vitro preparation in which microdissected afferent arterioles, a vascular segment crucial to glomerular hemodynamics, are perfused at a controlled pressuse. In addition, the role of prostaglandins were studied using various molecular and cellular biological approaches.
1) We studied the effect of 20-hydroxyeicosatetraenoic acid (20-HETE) in isolated microperfused rabbit afferent arterioles. We found that elevated vasal tone is required for 20-HETE to exert its vasoconstrictor action, which is endothelium-dependent and is partially mediated by cyclooxygenase products. In SHR,elevated renal 20-HETE production and increased afferent arteriolar tone co-exist during development of hypertension, with their synergistic actions contributing to the pathogenesis of hypertension.
2) The calcium antagonist is most wi
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dely used for treatment of hypertension. We found that calcium antagonists dilate afferent arterioles preconstricted with norepinephrine. Such dilation would render glomerular capillary pressure dependent on systemic blood pressure. Thus, in order for calcium antagonists to exert renoprotective effect by lowing glomerular capillary pressure, systemic blood pressure should be well controlled.
3) Studies with microdissected nephron segments have demonstrated that PGs and produed mainly in the vasculature including the glomerulus and collecting tubules. We cloned cDNA of the EP3 receptors, subtype of PGE2 receptor, from the rat kidney, and analyzed its intrarenal distribution and signal transduction mechanism. We found that mRNA of the EP3 receptors was expressed in the distal nephron, including the thick ascending limb and cortical collecting ducts, while their subtype EP3A and EP3B receptors were coupled to a decrease in intracellular cAMP and an increase in Ca2+ respectively, both of which are known to inhibit tubular transport. Thus the PG system appears to function at the site or vicinity of production, controlling water and electrolyte balances. Less
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