Mechanisms underlying the differential control of blood flow in the renal medulla and cortex

There is much evidence that the medullary circulation plays a key role in regulating renal salt and water handling and, accordingly, the long-term level of arterial pressure. It has also recently become clear that various regulatory factors can affect medullary blood flow (MBF) differently from cortical blood flow (CBF). It appears likely that the influence of hormonal and neural factors on the control of arterial pressure is mediated partly through their impact on MBF. In this review, we focus on the mechanisms underlying the differential control of MBF and CBF, particularly the relative insensitivity of MBF to vasoconstrictors such as angiotensin II, endothelin-1 and the sympathetic nerves. The vascular architecture of the kidney appears to be arranged in a way that protects the renal medulla from ischaemic insults, with juxtamedullary arterioles, the source of MBF, having larger calibre than their counterparts in other kidney regions. Indeed, recent studies using vascular casting methodology suggest that juxtamedullary glomerular arterioles are not the chief regulators of MBF, which is consistent with the idea that outer medullary descending vasa recta play a key role in MBF control. Release of vasoactive paracrine factors such as nitric oxide and various eicosanoids from the vascular endothelium, and probably also from the tubular epithelium, appear to differentially modulate responses of MBF and CBF to hormonal and neural factors. The prevailing intrarenal hormonal milieu and existing haemodynamic conditions also appear to strongly modulate these responses, indicating that multiple control systems interact to regulate regional kidney blood flow at an integrative level.