Summary

Kidney Function Restoration Program

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The renal cortical microcirculation delivers blood to the glomerular capillaries, where blood is filtered into the nephron. Pre- and postglomerular arteriolar tone is closely regulated to maintain a sufficient filtering pressure. The systems that control resistance of these arterioles remain a rich source of investigation. The goals of these studies are to better understand the physiology of glomerular blood flow and the potential dysfunctions that may contribute to renal failure and hypertension. Advances have been made both in methods to study these small-resistance vessels, such as intravital microscopy and isolated perfused afferent arteri-oles, and in studies of the hormones that regulate arteriolar resistance.

Glossary

Afferent arteriole: The small artery leading into the glomerular capillary, providing the major vascular resistance in the kidney.

Efferent arteriole: The smallest artery in the cortex, which emerges from the glomerular capillary and leads to either a peritubular capillary (in the outer cortex) or vasa recta (in the juxtamedullary cortex). This vessel has a relatively high resistance capacity.

Glomerular capillary: A capillary containing an intricate network of branches and anastomoses, where the filtration of the fluid component of blood passes into the nephron. Located only in the renal cortex.

Renal vascular resistance: The change in hydrostatic pressure due to the tone of the downstream vasculature.

References

1. Marchetti, J., Helou, C. M., Chollet, C., Rajerson, R., and Alhenc-Gelas, F. (2003). ACE and non-ACE mediated effect of angiotensin I on intracellular calcium mobilization in rat glomerular arteries. Am. J.

Physiol. Heart Circ. Physiol. 284(6), H1933-H1941.

2. Matsuda, H., Hayashi, K., Arakawa, K., Kubota, E., Honda, M., Tokuyama, H., Suzuki, H., Yamamoto, T., Kajiya, F., and Saruta, T. (2002). Distinct modulation of superficial and juxtamedullary arterioles by prostaglandin in vivo. Hypertens. Res. 25(6), 901-910.

3. Hansen, P. B., Hashimoto, S., Briggs, J., and Schnermann, J. (2003) Attenuated renovascular constrictor responses to angiotensin II in adenosine 1 receptor knockout mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 285(1), R44-R49. This study combined whole kidney function and isolated perfused isolated afferent arterioles from the adenosine type 1 receptor knockout mouse to assess the chronic absence of adenosine vasoconstriction control. The authors showed that the full vasoconstriction associated with Ang II required adeno-sine 1 receptors.

4. Inscho, E. W., and Cook, A. K. (2002) P2 receptor-mediated afferent arteriolar vasoconstriction during calcium blockade. Am. J. Physiol. Renal Physiol. 282(2), F245-F255.

5. Imig, J. D., Breyer, M. D., and Breyer, R. M. (2002). Contribution of prostaglandin EP2 receptors to renal microvascular reactivity in mice. Am. J. Physiol. Renal Physiol. 283, F415-F422.

6. Wang, D., Borrego-Conde, L. J., Falck, J. R., Sharma, K. K., Wilcox, C. S., and Umans, J. G. (2003). Contributions of nitric oxide, EDHF, and EETs to endothelium-dependent relaxation in renal afferent arteri-oles. Kidney Int. 63, 2187-2193.

7. Cavarape, A., Endlich, N., Assaloni, R., Bartoli, E., Steinhousen, M., Parekh, N., and Endlich, K. (2003). Rho-kinase inhibition blunts renal vasoconstriction induced by distinct signaling pathways in vivo. J. Am. Soc. Nephrol. 14(1), 261-264. This study introduces a novel regulator to the control of renal cortical microcirculation, the Rho/Rho kinase system. Though previously studied in VSMCs and other nonrenal tissue, this is the first attempt to identify the role of these agents in the renal cortex.

8. Yamamoto, T., Tada, T., Brodsky, S. V., Tanaka, H., Moiri, E., Kajiya, F., and Goligorsky, M. S. (2002). Intravital videomicroscopy of peri-tubular capillaries in renal ischemia. Am. J. Physiol. Renal Physiol. 282(6), F1150-F1155. These investigators report new observations with intravital microscopy in the rat kidneys. These results demonstrate both the advantages and limitations of this improved tool.

9. Gabriels, G., August, C., Grisk, O., Steinmetz, M., Kosch, M., Rahn, K. H., and Schlatter, E. (2003). Impact of renal transplantation on small vessel reactivity. Transplantation 75(5), 689-697.

10. Radermacher, J., Mengel, M., Ellis, S., Stuht, S., Hiss, M., Schwarz, A., Eisenberger, U., Burg, M., Luft, F. C., Gwinner, W., and Haller, H. (2003). The renal arterial resistance index and renal allograft survival. N. Engl. J. Med. 349(2), 182-184.

Capsule Biography

William J. Welch has worked extensively on intrarenal hormones that regulate tubuloglomerular feedback and its effect on renal function. He has used in vivo micropuncture to access the renal cortical vasculature and cortical nephrons. The interaction between single nephron function and vascular consequences has been the primary focus of his more than 60 published studies. He has used both normal and hypertensive models to show modu-latory roles for angiotensin II, thromboxane, nitric oxide, and superoxide in the control of GFR.

Section F

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