Intrarenal blood flow regulation probably affects long-term blood pressure homeostasis. We have previously shown that 5 Hz renal sympathetic stimulation inhibits a humoral renal depressor mechanism, otherwise activated when increasing perfusion pressure to an isolated kidney in a cross-circulation set-up. This inhibition was suggested to occur as a result of a reduction of renomedullary blood flow. Little is known about nervous blood flow regulation within the medulla. Therefore in this study, total renal (RBF), cortical (CBF) and papillary (PBF) blood flows were separately measured by ultrasonic and laser-Doppler techniques in Wistar rats during graded renal sympathetic stimulations. Periods of 15 min stimulation at 0.5, 2 and 5 Hz were performed in random order. RBF decreased at 0.5 Hz by 1%, at 2 Hz by 16% (P < 0.001) and at 5 Hz by 49% (P < 0.001). In a similar fashion (r = 0.73, P < 0.001), CBF decreased by 1%, 10% (P < 0.001) and 37% (P < 0.001), respectively. By contrast, PBF increased by 2% at 0.5 Hz and 4% at 2 Hz, while it decreased at 5 Hz, by 4% (P < 0.05, compared with 2 Hz). It seems therefore, that superficial renocortical and total renal blood flows are closely regulated by renal sympathetic nerves with increasing vasoconstriction at higher frequencies, while medullary blood flow, on the other hand, seems to be under strong local control, tending to offset neurogenic flow restrictions.

It has long been recognised that the kidneys take part in blood pressure control via both their exocrine and endocrine functions. An endocrine antihypertensive function of the renal medulla has been proposed. The renal medullary depressor substances ("medullipins"), are released in response to increased renal perfusion pressure. It has been suggested that the release of "medullipin" is controlled via changes in renal medullary blood flow. Recent observations also suggest that renal medullary blood flow is involved in the control of the pressure/natriuretic-diuretic action of the kidney. In this review we outline a unified hypothesis for blood pressure control via a combination of the plasma volume regulating pressure-natriuresis mechanism and the powerful antihypertensive actions of the "medullipins" (i.e. vasodilatation, inhibition of sympathetic drive and a diuretic action). It is hypothesised that the activity of both these systems are under control by renal medullary blood flow.

The renal medulla harbours powerful humoral antihypertensive mechanisms, as earlier explored in unclipping experiments on renal hypertensive rats or in normotensive isolated kidneys cross-circulated at increased perfusion pressures from 'donor rats', in which renal function also seemed to be affected. Injection of the renomedullary factor medullipin I (Med I; formerly ANRL) mimics these haemodynamic responses, and Med I seems to be one of the most important mediators of the depressor effects. The present study was performed to analyse further the haemodynamic and, particularly, the renal effects of Med I, using anaesthetized intact WKY rats and constant-pressure perfused (90 mmHg) isolated WKY kidneys, cross-circulated by these intact 'donor' rats. Mean arterial pressure (MAP), heart rate (HR) and renal function were followed for one 30-min period before and two 30-min periods after injection of 1 mg Med I (M; n = 7) or an equal volume of saline as control (C; n = 13). In the intact 'donor' WKY, MAP and HR remained largely constant in C during the three periods, being 126 +/- 5, 125 +/- 5, and 120 +/- 5 mmHg, while MAP fell in the M group after Med I, from 121 +/- 5 to 107 +/- 7 and 107 +/- 5 mmHg (P less than 0.05), and also HR tended to decrease in M. Renal resistance (RR) fell while renal plasma flow (RPF) and glomerular filtration rate (GFR) increased significantly (P less than 0.05) after Med I in the M donor rats despite their MAP reduction. However, in the constant-pressure perfused, cross-circulated kidneys the RR, RPF and GFR changes were clearly more pronounced (P less than 0.01) and also diuresis, natriuresis, osmolar excretion and osmolar clearance increased significantly after Med I (P less than 0.01). In conclusion, the present results support the view that Med I not only has important and long-lasting depressor effects but also affects renal function in important ways, inducing vasodilatation and increasing GFR, RPF, diuresis and sodium-osmolar excretion.

Blockade of NO synthesis with N-omega-nitro-L-arginine (L-NNA) inhibits the vasodepressor response seen in intact Wistar assay rats in which isolated kidneys perfused via an extracorporeal circuit are perfused at high pressure. This study explores the renal and haemodynamic changes associated with this inhibition. Isolated kidneys (IK) were perfused at high pressure (175 mmHg) by a pump in series with intact Wistar assay rats in which blood pressure (BP), haemodynamics and renal function were studied. Nitric oxide (NO) synthesis was blocked by L-NNA (2.5 mg kg-1) in 13 experiments (175NO) while 14 control experiments (175C) were performed. IK was perfused at 90 mmHg in seven experiments (90C). The BP drop in the 175C assay rat was blocked by L-NNA in 175NO (P < 0.01). However, when the blockade was reversed with L-arginine infusion (20 mg kg-1 min-1) BP declined also in 175NO. Effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) fell dramatically after L-NNA in both the assay rat and in IK despite a high perfusion pressure. The marked increase in filtration fraction (FF) after L-NNA suggests a dominating postglomerular vasoconstriction. The natriuretic response in IK to 175 mmHg was also markedly blunted by L-NNA. We conclude that NO blockade inhibits the renomedullary depressor mechanism probably by restricting renal blood flow, and also blunts the pressure induced natriuretic response as a result of a reduced sodium filtration. Finally, the autoregulation of whole kidney blood flow seems to be more efficient although set at a higher level of vasoconstriction.

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