Nitric Oxide (NO) plays an important role in the renal, cardiovascular, nervous and immune systems (reviewed by Reid, I. 1994). The presence of high concentrations of Type I nitric oxide synthase (NOS-I) has been demonstrated in the macula densa cells of the kidney. The objectives of this research project are to examine the role of NO expressed in the macula densa cells in renin secretion and renal function. The aim of this project is to use gene targeting and transgenic techniques established at the CGR in Edinburgh to mark and isolate NOS-I expressing macula densa cells, and generate conditionally immortalised cell lines using the H-2Kb -tsA58 transgenic mouse (Jat, P.S. et al., 1991). Using the conditionally immortal cell lines generated, the role of NO in the control of (i) renin secretion from the juxtaglomerular cells (JG), (ii) renal blood flow, (iii) glomerular filtration rate, (iv) tubuloglomerular feedback and (v) renal sodium excretion will be examined. The generation of these conditionally immortal cell lines will be of immense use to the further understanding of the renin angiotensin system, renal function, hypertension and cardiovascular research.
Jat, P. S., Noble, M. D., Ataliotis, P., Tanaka, Y., Yannoutsos, N., Larsen, L., Kioussis, D. (1991) Direct derivation of conditionally immortal cell lines from an H-2Kb -tsA58 transgenic mouse. Proc. Natl. Acad. Sci USA 88: 5096-5100.
Reid, I.A. (1994) Role of Nitric Oxide in the regulation of renin and vasopressin secretion. Frontiers in Neuroendocrinology 15: 351-383.