EFFECT OF VASOACTIVE AGENTS IN THE ISOLATED GLOMERULUS

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Problem: There is a considerable amount of data in the literature which suggests that single nephron glomerular filtration rate is influenced by vasoactive hormones. These hormones include the prostaglandins, angiotensin II, norepinephrine, and vasopressin. The mechanisms by which these hormones modulate glomerular filtration have until now been investigated almost exclusively under in vivo conditions. Under these conditions, the singular effect of one hormonal manipulation is difficult to decipher due to the many systemic effects of these agents and the possible hormone-hormone interactions that may occur. Objectives: In the present project an investigation of the effects of the vasoactive agents: PGE2, PGI2, bradykinin, acetylcholine, angiotensin II, norepinephrine and vasopressin on the determinants of glomerular filtration rate (PGC, Pi GC, Kf) is proposed. A second aim of this project will be to quantify the production of TxB2, PGE, and PGI2 by a single glomerulus. Further, the response of this production to the vasoactive agents: angiotensin II, norepinephrine, and vasopressin will be measured. METHODS: The above objectives will be approached with the use of a technique recently developed in this laboratory: the isolated perfused glomerulus. This technique allows one to measure the effect of a single vasoactive compound under controlled conditions which eliminate systemic effects and minimize hormone-hormone interactions. It also allows one to measure the prostaglandin and TxB2 production by a single glomerulus under physiologic flow rates. Briefly, one dissects a single glomerulus free with intact afferent and efferent arterioles. This glomerulus which retains an intact capsule is transferred to the perfusion apparatus which utilizes two sets of pipettes: one for perfusion via the afferent arteriole as well as measurement of glomerular hydrostatic pressure and, the second, for the collection of fluid from the efferent arteriole. With this technique one can measure PGC, Pi GC, SNGFR, QA and filtration fraction and one can calculate KF.