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The Physiology of the Renal Circulation

Burton-Opitz and Lucas (1911) were the first to note the striking constancy of renal blood How in the face of wide variation in perfusion pressure-a phenomenon which struck them as remarkable in the light of their earlier demonstration that the renal vessels were capable of intense vasoconstriction, when the sympathetic nerves were stimulated. Rein (1931) confirmed that observation and extended it by contrasting the responses of the kidney’s blood vessels to those of the femoral, mesenteric and carotid vascular beds, which were influenced much more by changing perfusion pressure. The ‘autoregulation’ of renal blood flow despite changes in arterial blood pressure has had too much impact on current thinking: the concept, unfortunately, has gradually broadened so that a consensus of Opinion today might indicate the belief that the renal circulation is relatively autonomous and that renal perfusion is fixed. In fact renal perfusion shows wide variation in response to external s

Renal Blood Flow in Health and Disease

The contribution to disordered renal function of deviations of renal blood flow from the normal obviously cannot be ascertained without definition of normal, which is far from a trivial problem. Renal perfusion is influenced by age, position, time of day, diet, activity and emotional state. These observations raise the question: What is ‘normal’ renal blood flow? For example, renal blood flow falls with increasing age, with assuming the upright position and with restriction of salt intake. Obviously, renal blood flow in a recumbent 20-year-old healthy youth who eats 15 g of salt daily exceeds considerably that in a 70-year-old man who is standing, and who ingests 2 g of salt daily, but is neither more nor less normal in the former than in the latter. In both individuals renal function serves to maintain a normal internal milieu, although the limits over which the kidney will respond are narrowed in the elderly individual. In some states such as severe hypotension (Selkurt 1946) o

Other Endogenous Vasoactive Factors and Metabolic Products

There has long been interest in the role of the products of metabolism as determinants of vascular tone in various vascular beds (Furchgott 1966, Haddy & Scott 1970). Such products, including both specific substances such as the adenine nucleotides, lactic acid, hydrogen, potassium and magnesium ions and a general increase in osmotically active metabolites, dilate most vascular beds. It is potentially important that all of these agents are vasoconstrictors only in the special case of the renal vasculature (Johnson & Lepley 1966, Haddy & Scott 1970, Caldicott & Hollenberg 1970, Wexler & Kao 1970). The reduction in renal blood flow that characteristically occurs in shock, after a period of renal ischaemia or with heavy exercise may be attributable to the products of metabolism. Before concluding that metabolic processes play an important role as a determinant of cortical perfusion, it is well to recall the lavish perfusion that the cortex enjoys: an average fl

Prostaglandins and the Kidney

Prostaglandins are a family of biologically active lipids synthesized in viva from a number of essential fatty acid precursors, especially arachidonic acid (Bergstrom et al. 1968). Although they were identified in the early 1930s, only in the last decade have they generated widespread interest, especially in relation to the kidney. They have been detected in almost every tissue and body fluid, but the concentrations are especially high in the kidney (Lee et al. 1967, Crowshaw 1971); their production increases in response to an astonishingly diverse array of stimuli; a remarkably broad spectrum of effects occurs in virtually every system in response to minute amounts. A powerful new tool for exploring the role of prostaglandins arose from the discovery that non-steroidal anti-inflammatory agents such as aspirin, indomethacin and meclofenamate interfere with prostaglandin synthesis (Vane 1971). Synthesis of the prostaglandins is accomplished sequentially by a series of microsomal e

Adrenergic Factors

The kidney receives a rich nerve supply from the sympathetic nervous system, as indicated in the preceding chapter. While it is traditional to discuss the role of local, neural release of catecholamines and of circulating catecholamines together, the latter rarely play much of a role quantitatively in controlling the renal circulation (Celander l954). The distribution within the kidney of the sympathetic neurone supply has received considerable attention: norepinephrine-containing nerves are found in the major arterial vessels in the cortex, up to the afferent arterioles and the juxtaglomerular apparatus (Nilsson 1965, Mc. Kenna & Angelakos 1968, Fourman 1970, Ljungqvist & Wagermark 1970, Norvell et al. 1970). All studies agree that neither the intraglomerular capillaries nor the tubules appear to have such an innervation. There is still debate concerning the sympathetic nerve supply of the efferent arterioles, which Fourman (1970) and Ljungqvist and Wagermark (1970) iden

The Renin-Angiotensin System

Angiotensin II, an octapeptide, is the most active endogenous vasoconstrictor agent identified to date, with an especially marked influence on the renal vasculature. A marked reduction in blood flow to the kidney occurs with doses that are well below those required to induce a pressor response (Mandel & Sapirstein 1962, Schmid 1962, DeBono et al. 1963, Hollenberg et al. 1972, 1975, 1976). A number of reviews have stressed the possibility that angiotensin functions as a renal hormone (Schmid 1962, Brown et al. 1972, sokabe 1974). Renin, a proteolytic enzyme, is produced primarily in the renal cortex, with much smaller amounts being found in the uterus, placenta, salivary glands, brain and some blood vessels (Smeby & Bumpus 1968). In the kidney it is synthesized in specialized cells in the juxtaglomerular apparatus in intimate contact with the vascular pole of the glomerulus; thus secretion occurs immediately adjacent to the afferent and efferent arterioles (Barajas 1972).

Control Mechanisms Autoregulation

It should be apparent from this survey that the renal vasculature potentially plays a number of functional roles, many of which are as yet incompletely defined. The control of regional perfusion rates within the kidney and of the intrarenal distribution of blood flow has major consequences not only for overall cardiovascular homeostasis but also for renal function. An analysis of the determinants of regional intrarenal perfusion rates requires an examination of the effects of perfusion pressure and the influence of a number of endogenous vasoactive factors, including the renin-angiotensin system, norepinephrine and the sympathetic nervous system, the prostaglandins and the products of metabolism. Renal blood flow remains almost constant over a wide range of perfusion pressure, from about 80 to 180 mmHg (Selkurt 1946b); glomerular filtration rate also remains constant over much of this range (Forster & Maes 1947). The constancy has utility in preventing wide swings in the lo