Chapter 318 - Kidney

Abstract

This chapter focuses on cell-to-cell communication within the kidney and highlights signal transduction among different cells. The vascular smooth muscle cells (VSMC) of renal microvessels respond to local paracrine factors in addition to circulating hormones and sympathetic nerve activity. Contraction of VSMCs is regulated by physical and chemical factors, with multiple signal transduction pathways coupling agonist-receptor interactions to [Ca2+]i followed by activation of the actin-myosin contractile machinery. Endothelial cells are in contact with blood elements, and subjected to hemodynamic forces such as hydrostatic pressure and shear stress. The lumen hydrostatic pressure tends to distend the arterioles, causing a contractile myogenic response, whereas the shear stress, depending on the flow velocity, causes release of vasodilator agents, including nitric oxide (NO), cyclooxygenase (COX) products, and endothelium-derived hyperpolarizing factor (EDHF), and vasoconstrictor factors, including endothelin-1 (ET), cytochrome P450 (Cyt-P450) products, and COX2 derivatives. Microsomal heme-oxygenase (HO) catalyzes the metabolism of heme to form carbon monoxide (CO), biliverdin, and free iron. Two isoforms, HO-1 and HO-2, are expressed in the kidney. Constitutively active HO-2 is ubiquitous, present in the renal vasculature and in almost all nephron segments. Under basal conditions, inducible HO-1 appears to be at low levels or absent from renal structures. Intrarenal bradykinin has vascular actions in the cortex and medulla mediated primarily, if not exclusively, by B2 receptors. The main action of bradykinin is vasodilatation, mediated by a predominance of B2 receptors on endothelial cells, which stimulate phospholipase C (PLC) production and increase [Ca2+]i to stimulate eNOS activity and release endothelium-derived hyperpolarizing factor (EDHF)/epoxy-eicosatrienoic acids (EET).