Mechanisms underlying pressure-related natriuresis: the role of the renin-angiotensin and prostaglandin systems. State of the art lecture.

Abstract

SUMMARY It has long been known that increments in renal perfusion pressure can induce an elevation of urine sodium excretion without changing renal blood flow or glomerular filtration rate. The mechanism underlying this pressure-related natriuresis remains undefined, although the interest in its elucidation has been stimulated by the notion that it may constitute the central phenomenon through which the kidney regulates blood volume and, thereby, blood pressure. Recently, the use of novel experimental techniques has disclosed some important clues about changes in renal hemodynamics that, along with changes in renal humoral regulators, allow us to visualize a possible sequence of events responsible for pressure-related natriuresis. According to this hypothesis, the autoregulatory responses responsible for maintaining glomerular filtration rate are elicited in preglomerular vasculature by changes in renal perfusion pressure. These myogenic responses are coupled through Ca 2+ entry in juxtaglomerular cells with inversely related changes in the release of renin and, consequently, with the amount of angiotensin II generated in renal interstitium. The release of renin from juxtaglomerular cells is modulated by the synthesis of prostaglandin I 2 from the adjacent endothelial cells. Interstitial angiotensin II could influence sodium tubular reabsorption directly by stimulating sodium transport in proximal renal tubules and indirectly by altering medullary blood flow and, thereby, medullary interstitial pressure. In the renal medulla, the effects of interstitial pressure on sodium reabsorption can be amplified by the release of prostaglandin E 2 from interstitial cells. A deficient regulation of this relationship could result in a shift of the pressure-natriuresis curve, leading to hypertension. (Hypertension 11: 724-738, 1988) KEY WORDS • prostaglandins • renin-angiotensin system • medullary blood flow • renal blood flow • glomerular filtration rate • hypertension I T has long been recognized that the kidney alters urine flow and sodium excretion 1 2 in response to acute changes in renal perfusion pressure (RPP).3 4 Since the glomerular filtration rate (GFR) is well autoregulated (Figure 1), pressure-related natriuresis is the result of decreased reabsorption of sodium by the renal tubules rather than increased filtered load. 4 The mechanisms responsible for changes in sodium reabsorption have not been fully denned, but interest in its elucidation has been maintained ever since pressure-related natriuresis was conceptually placed at the

Urinary prostaglandin and prostaglandin metabolite excretion in patients with essential hypertension or hypertension with renal artery stenosis

“…A number of studies have shown that in the case of stimulation of the renin-angiotensin system, especially as a result of renal ischaemia, renal eicosanoid production rises [1][2][3][4][5][6][7][8][9]. Since a significant renal artery stenosis is a situation of renal ischaemia, it might be expected that this condition results in an elevated renal prostaglandin production.…”

“…Recent studies in humans have revealed that in subjects with renal artery stenosis, systemic plasma levels of prostaglandin E 2 (PGE 2) are higher than in patients with essential hypertension and that the renal vein plasma levels of PGE 2 are higher on the stenotic side than on the non-stenotic side [3,4]. Also levels of PGI2 and of PGA 2 were shown to be elevated in renal artery stenosis in humans [5][6][7][8][9].…”

“…These microcirculatory changes act to preserve glomerular filtration fraction in states of impaired renal perfusion pressure [8,13]. If renal perfusion pressure declines, PGI 2 production in the endothelial ceils of the vas afferens rises [7]. The PGI 2 in turn potentiates renin release by the juxtaglomerular apparatus [12,14].…”

Diuretic effects of L-threo-3,4-dihydroxyphenylserine(L-threo-DOPS) in anesthetized rats.

“…On the other hand, humoral factors such as prostaglandins and the renin angiotensin system (21,22) are also reported to be involved in the pressure diuresis. How ever, the precise mechanisms and tubular sites in which the phenomenon occurs remain to be determined (13).…”

Role of nitric oxide and prostaglandin in the maintenance of cortical and renal medullary blood flow

“…However, identification of their mechanism of action is of critical importance to understand how the kidney influences the equilibrium of body fluids and blood pressure (1)(2)(3)(4). Of particular interest are the effects of prostaglandins (PGs) and nitric oxide (NO), both of which exhibit a high rate of synthesis in the renal medulla (5)(6)(7) and in the renal vascular endothelium (8). In fact there are observations showing that the blockade of NO produces, in the rat, a decrease in medullary circulation which leads with time to excessive sodium retention and a sustained increase in blood pressure (9,10).…”