The Nature of Experimental Second-set Kidney Transport Rejection: 5. Nephrograms in Second-set Reactions and Their General Significance in Acute Renal Failure

The detailed characteristics of a nephrogram are more meaningful if studied in relation to the corresponding arteriogram. The appearance of a nephrogram in several forms of acute renal failure, including the second-set kidney transplant reaction, can be explained by a diversity of function among the nephrons. Those nephrons derived from outer cortical glomeruli are considered to be mainly geared to excretion and reabsorption whereas those nephrons derived from inner cortical glomeruli, are mainly geared to reabsorption and concentration. A nephrogram appearing in a severely oliguric or anuric kidney can be explained on the basis that outer cortical filtration has been seriously reduced or has ceased while inner cortical filtration continues but the filtrate is concentrated and reabsorbed. A kidney involved in this haemodynamic upset would more precisely be diagnosed as being in a state of acute excretory renal failure. The severe interference with excretory function is compatible with a total renal blood flow reduced by only 20-40 per cent.After several hours involvement in the severe haemodynamic upset evoked by a second-set kidney transplant reaction, inner cortical perfusion fails and at this stage no nephrogram is observed. A similar lack of a nephrogram associated with inadequate cortical perfusion was observed at 24 hr after subjecting a kidney to 2 hr total warm ischaemia which causes cortical necrosis.These principles permit a review of intravenous pyelographic techniques to be made with the recommendation of using small physiological doses of anti-diuretic substances, about half the currently recommended dose of contrast and free but not excessive access to water because the above injected doses of anti-diuretic hormone act maximally during an established water diuresis.     

The Nature of Experimental Second-set Kidney Transplant Reaction: 2. The Mimicking of the Haemodynamic Upset by Pharmacological and Other Means

The second-set kidney transplant reaction involves in its early stages vasoconstriction of the outer cortex. This is a phenomenon occurring widely in medical and surgical conditions and is precipitated by stimuli of pharmacological, nervous, immunological and ischaemic origins. Various stimuli elicit varying degrees of outer cortical vasoconstriction and although the renal vascular response usually involves all segments, the outer cortical segments can remain in spasm when the more proximal segments have been pharmacologically vasodilated. Vasoconstriction in the outer cortex leads to impaired renal function and explains the transient anti-diuretic action of drugs such as nor-adrenaline, Hypertensin-Ciba (Ciba), ergot preparations, vasopressin and Priscol (Ciba) which can mimic the vasoconstriction induced by warm and cold ischaemia and the second-set reaction. The marked vasoconstricting ability of the vessels of the outer cortex, as part of the renal response to various stimuli, is seen as an unfortunate by-product of an evolutionary mechanism designed to cater for constant adjustments in the handling of salt and water. The factors mediating the second-set reaction remain obscure since vasodilators, α-adrenergic blockers and smooth muscle paralysers are all ineffective in combating the vasoconstriction.     

The Nature of Experimental Second-Set Kidney Transplant Rejection: 3. The Role of Complement

Second-set kidney transplant reactions occur in decomplemented dogs. The microscopic features of the reaction under such conditions indicate that the typical acute inflammatory reaction has occurred. Since the factors (presumably antibodies) mediating the second-set reaction are not dependent on complement fixation it is unlikely that HL-A antibodies, which are dependent on complement fixation for cytotoxicity, can be implicated in so-called hyperacute rejection (i.e. second-set rejection) in humans. The microscopic features of a genuine second-set reaction in humans are identical to those originally described in the dog. Since the first observable sign of the second-set kidney reaction is vasoconstriction of the outer cortical vessels, it is essential to establish how a severe antigen-antibody reaction can evoke such a rapid destruction of a kidney allotransplanted to a previously sensitized recipient. It is glomerular basement membrane which first bears the brunt of the second-set reaction. Tubular damage appears to follow gross ischaemia resulting from afferent renal vasoconstriction. Since the antigens of renal basement membrane are not represented on the lymphocytes, serious problems arise in attempting to assess renal histocompatibility by lymphocyte markers.     

The Nature of Experimental Second-set Kidney Transplant Rejection: 6. The Ultrastructural Features: An Immunological Dilemma

Recipients which have already rejected allografts of skin react rapidly and violently against a subsequently allotransplanted kidney. This is the renal allotransplant second-set reaction, the primary manifestation of which is a sudden severe afferent vasoconstriction. As a result of this vasomotor disturbance, red blood cells and platelets sometimes aggregate in the glomerular capillaries and the renal tubule cells suffer necrosis. The precipitating cause of the vasomotor disturbance has not been determined but platelet aggregation can be ruled out since in ancrod (Arvin)-treated recipients this does not occur although a second-set reaction develops. No evidence of glomerular basement membrane damage, due either to anti-glomerular basement membrane antibodies or antigen antibody complexes, was detected by the current ultrastructural studies. Since in these experiments the recipients were previously sensitized by skin allografts, a cytotoxic factor which is directed against specific renal components should not be expected to mediate the renal allotransplant second-set reaction. There is, at some structural level, common antigenicity between skin, heart and kidney and, since all three tissues succumb to changes in their vascular systems, it suggests some common antigenic factor in blood vessels. The features of the renal second-set reaction have been compared with other established renal immune disease states but none can compare in rapidity and severity of action with the second-set reaction.     

Development of the intrarenal vascular system of the puppy kidney

This study investigates the development of the vascular system of the puppy kidney (1-21 days after birth) after preparing casts of the renal vessels. At two days, the intrarenal vascular system distal to the afferent arteriole is strikingly different than that of the adult. The glomeruli of the outer cortex consist of a single dilated vessel while those of the mid and inner cortex possess an increasingly larger number of capillary loops. The efferent arterioles vary greatly in appearance from outer to inner cortex. Those in the nephrogenic zone are characteristically short and narrow and join a larger venous vessel termined a sinusoidal capillary. An efferent system somewhat similar to that of the adult is seen in the mid and inner cortex. One of the most obvious differences noted between the puppy and adult kidney is the relative lack of peritubular capillary networks throughout the cortex of the puppy kidney. The puppy possesses large, irregular vessels termed sinusoidal capillaries. The most rudimentary sinusoids are found in the outer cortex with more mature vessels in the inner cortex. The vascular arrangement of the efferent arteriole and sinusoidal capillary appears as a post-glomerular shunt. Functionally, the shunt would direct blood flow away from the proximal tubule and thus could result in a low extraction ratio and Tm for secreted solutes.     

Development of the intrarenal vascular system of the puppy kidney.

This study investigates the development of the vascular system of the puppy kidney (1-21 days after birth) after preparing casts of the renal vessels. At two days, the intrarenal vascular system distal to the afferent arteriole is strikingly different than that of the adult. The glomeruli of the outer cortex consist of a single dilated vessel while those of the mid and inner cortex posses an increasingly larger number of capillary loops. The efferent arterioles vary greatly in appearance from outer to inner cortex. Those in the nephrogenic zone are characteristically short and narrow and join a larger venous vessel termined a sinusoidal capillary. An efferent system somewhat similar to that of the adult is seen in the mid and inner cortex. One of the most obvious differences noted between the puppy and adult kidney is the relative lack of peritubular capillary networks throughout the cortex of the puppy kidney. The puppy possesses large, irregular vessels termed sinusoidal capillaries. The most rudimentary sinusoids are found in the outer cortex with more mature vessels in the inner cortex. The vascular arrangement of the efferent arteriole and sinusoidal capillary appears as a post-glomerular shunt. Functionally, the shunt would direct blood flow away from the proximal tubule and thus could result in a low extraction ratio and Tm for secreted solutes.     

Maturation of glomerular blood flow distribution in the new-born dog

1. Glomerular blood flow distribution was studied in seventy-eight new-born mongrel dogs aged 1-40 days by measuring the distribution of radioactive labelled microspheres within the kidney.2. The microsphere technique was found to be a valid indicator of glomerular blood flow distribution for the new-born dog since (a) the spheres were completely extracted by the kidney, (b) more than 95% of the spheres were trapped in glomerular capillaries, (c) the spheres were evenly distributed within any specific region of the kidney and, (d) the spheres did not interfere with renal haemodynamics.3. Plasma flow per gram tissue to inner cortical glomeruli, relative to that to outer cortical glomeruli, the IC/OC flow ratio, was high at birth, decreased over the first 2 weeks of life and remained relatively constant thereafter. Plasma flow per gram tissue to the outer cortex increased over the whole 40 day period while that to the inner cortex decreased slightly and then increased after 2 weeks.4. The IC/OC flow ratio decreased in a curvilinear fashion as blood pressure rose with maturation. Acute increases or decreases in blood pressure in any animal produced decreases or increases, respectively, in the IC/OC flow ratio.5. There was no correlation between the IC/OC flow ratio and renal extraction of p-amino-hippurate (E(PAH)).6. There was histological evidence that glomerular differentiation persists for 2 weeks during the post-natal period in the dog. This continuing post-natal glomerulogenesis takes place only in the outer cortex.7. These results are consistent with the hypothesis that an important factor in renal maturation is a redistribution of blood flow within the kidney. As the animal matures a greater fraction of the total glomerular blood flow goes to outer cortical glomeruli. This is due partly to the continuing glomerular differentiation taking place in the outer cortical region and partly to the increasing arterial blood pressure occurring with maturation.     

Renal anatomy of the manatee,Trichechus manatus,linnaeus

The manatee kidney is com posed of several closely apposed lobes. These are formed by cortical folds (plicae corticales) that completely isolate the medullae, except where the medullae of adjacent lobes are partially fused. The cortex is continuous; its folds usually are separated, but only partially, by interlobar septa ex tending from the renal capsule. The cortex makes up ～57% of renal mass in adults and 68% in the calf. There are about 3 million glomeruli per kidney. The average is somewhat less than that expected of an adult eutherian of equal mass. The glomeruli, however, are large; they form 7.38%±1.33 of cortical mass, which is above that for at least ten unrelated adult eutherians. The number of glomeruli per gram of cortex is considerably greater in the calf than in the adult. The medullae are about 43% of renal mass. The cortico-medullary thickness ratio is 0.08 to 0.24. All terminal collecting ducts open at a crater (cra-tera cribrosa) of varying depth. Hair-pin loops occur at all levels of medulla, and apparently all loops bend at their thick segment. Cortical loops occur in the medullary rays. Vascular bundles were evident at the cortico-medullary border and thin tubules extended into the medulla from the central ends of the medullary rays (cortical) in seven out of the nine kidneys. The renal pelvis is separated from the central ends of the cortical folds by delicate fascia through which pass the interlobar vessels. There are no fornices and no infundibula. The collagenous tissue of the pelvic wall extends across most of the pelvic surface of the outer medulla.     

Comparison of size of juxtamedullary and outer cortical glomeruli in normal adult kidney

Summary Abnormally large glomeruli are susceptible to hyperfiltration-associated sclerosis. We used an established morphometric method to test the general belief that juxtamedullary glomeruli are larger than those in the outer cortex, in a population with no clinical or pathological evidence of renal disease. Overall, juxtamedullary glomeruli were significantly larger, but this varied according to the amount of global glomerulosclerosis present. Global sclerosis increased with age, particularly in the outer cortex, and the ratio of juxtamedullary to outer cortical glomerular size showed a positive correlation with overall, and outer cortical, global sclerosis. Thus in the truly normal adult kidney, juxtamedullary glomeruli are not significantly larger than outer cortical glomeruli. However, global sclerosis increases with age and is most marked in the outer cortex, and this leads to compensatory enlargement of predominantly the juxtamedullary glomeruli. These findings suggest that in single kidneys, or in conditions characterised by ischaemic glomerulosclerosis such as hypertension, morphological changes related to hyperfiltration may appear first, and therefore become most severe, in juxtamedullary glomeruli.     

Renal microvasculature of the rainbow trout, Salmo gairdneri: scanning electron microscopy of corrosion casts of glomeruli

Scanning electron microscopy of corrosion casts of blood vessels permits detailed and accurate study of the microcirculation. The present study examined the renal microvasculature of the rainbow trout, Salmo gairdneri. The conventional picture of a glomerulus with one afferent arteriole was common, but glomeruli were often supplied by two afferent arterioles. In the majority of these, the intrarenal artery gave rise to a single afferent arteriole that branched to form two smaller vessels before reaching the glomerulus. Glomeruli with two afferent arterioles that arose independently from the intrarenal artery also occurred. The majority of glomeruli had a single efferent arteriole, but a proportion of glomeruli had two efferent arterioles. Efferent arterioles were smaller in diameter than the afferent arterioles. The glomerular capillaries were arranged in lobules, with few anastomoses between lobules, so that, for glomeruli with two afferent or two efferent arterioles, vascular perfusion and thus filtration within discrete lobules is probable.     

Topography and structure of vasculature in developing cortex of rat kidney

Summary Young Wistar and SIV rats fixed by retrograde vascular perfusion were used for scanning and transmission electron microscopic, as well as light microscopic observations of the developing renal cortex and its vasculature. The latter was additionally observed by scanning electron microscopy of vascular casts effectuated by injection of methacrylate into the renal blood vessels.Disappearance of the initial nephron anlages — the vesicles — took place in the observed animals 2–3 days after birth, and another 2–3 days later the S-shaped bodies with the developing glomeruli differentiated into more advanced nephrons. The vascular system in the developing renal cortex consists of arterial supplying vessels, the sinusoid-like capillaries, and, continuous with the latter, large vessels which terminate in the arcuate vein. The arterial vessels assume their adult pattern already in the differentiating kidney, except their terminal — peripheral branching which is represented by arterial capillaries continuous with the drainage system. When nephronogenesis terminates the arterial capillaries are transformed into the young afferent vessels and the peripheral plexus of sinusoid-like capillaries receives its blood supply from the young efferent vessels. The sinusoid-like capillaries and large vessels give origin to the peritubular network of capillaries in the adult kidney, although their differentiation continues once nephronogenesis has been accomplished. They show some ultrastructural characteristics similar to those observed in sinusoids of other organs and they also differentiate in the same manner, by a conformation to the growing tubules.This work is dedicated to Professor Otto Bucher, M.D. (Lausanne), in honour of his 65th birthdayThe author wishes to thank Mrs. Madeleine Wirth and Miss Solange Gros for their excellent technical assistance     

Aspects of renal vascular organization and early vascular tubular relations of the marsupial Isoodon obesulus

Renal vascular tubular relationships were studied in the marsupial Isoodon obesulus (the common brown bandicoot). The microcirculation was filled with colored silicone rubber by intra-arterial injection of the intact kidney. Nephrons were defined by the injection of silicone rubber of a contrasting color into the space of Bowman's capsule in thick, cleared slices of renal tissue. The details of the vascular tubular relationship in this marsupial are strikingly similar to relationships previously described in true mammalian kidneys. An unusual feature is a wide (600μ) glomerulus-free zone at the outer cortex. This zone contains the proximal and distal convoluted tubules of the most superficial cortical nephrons and is perfused by efferent vessels from glomeruli in superficial strata of the cortex.     

The renal cortical lymphatic system in the rat,hamster, and rabbit

Rat, hamster, and rabbit renal cortical lymphatics were examined by light and electron microscopy. Rat and hamster kidneys possessed both intra- and interlobular lymphatics that were structurally similar at the light microscopic level. Ultrastructural examination of the hamster lymphatic endothelium, however, revealed an unusual arrangement of cytoplasmic extensions not seen in the other two species. The intralobular lymphatics were related primarily to tubules, afferent arterioles, and renal corpuscles and were consistent with lymph formation from both plasma filtrate and tubular reabsorbate. Interlobular lymphatics were seen in connective tissue associated with the interlobular blood vessels. Rabbit cortex contained only interlobular lymphatics. Cross-sectional area, maximum diameter, volume density, and profile density were determined by stereological measurements using a computer-based image analyzer. The morphological data from the rat were used, in combination with published values for lymph flow, to calculate the rate of lymph formation per unit area of endothelium in lymphatics of the renal cortex. Among kidneys fixed by retrograde perfusion, the cortical lymphatic system was most extensive in maximum diameter, volume density, and profile density. It was smallest in the rabbit and intermediate in the rat. Lower volume and profile density were found for rat kidneys fixed by the dripping technique. It was concluded that: (1) tubular reabsorbate probably contributes to renal lymph in the rat and hamster, but not in the rabbit; (2) significant differences exist in the extent of the renal lymphatic systems among the three species, with the hamster kidney having the richest network and the rabbit the poorest; (3) the method of fixation influences the measured size and density of renal cortical lymphatics; and (4) the estimated rate of lymph formation in the kidney of the rat is roughly comparable to that in the dog.     

The pathogenesis of chronic renal failure

The pathogenesis of terminal renal failure is discussed. The following are distinguished: 1. Renal failure occurring against a background of decompensated benign nephrosclerosis, primary and secondary malignant nephrosclerosis, and stenosis of the renal artery. 2. Renal failure caused by loss of glomeruli. It is pointed out that in most glomerulopathies, including diabetic glomerulopathy and renal amyloidosis, terminal renal failure only develops when accompanying disease of the postglomerular vessels leading to interstitial fibrosis impairs the outflow of blood from the glomerulus to such an extent that no more urine is produced. 3. Renal failure in disease of the tubules themselves. It is emphasized that acute renal failure only becomes chronic when interstitial fibrosis develops from the interstitial edema occurring in the early stage of the disease. 4. Renal failure occurring in primary diseases of the renal cortical interstitium. The chronic sclerosing renal diseases arising from acute interstitial nephritis are dealt with, as also are reflux nephropathy, incomplete obstructive nephropathy, analgesic nephropathy, and chronic interstitial rejection reactions in transplanted kidneys.     

The renal cortical lymphatic system in dogs with unimpeded lymph and urine flow

The distribution and extent of the lymphatic circulation in the renal cortex was analyzed in three dogs under conditions of unimpeded lymph and urine flow. The kidneys were drip fixed with acrolein in vivo, and cortical tissue strips were prepared for light and electron microscopic examination. Analysis of 90 tissue strips revealed 38 cortical lymphatics, one third of which were intralobular in position. The intralobular lymphatic capillaries were related primarily to tubules, afferent arterioles, or renal corpuscles. The remainder of the lymphatics were located in interlobular connective tissue areas in association with the interlobular blood vessels. Interlobular lymphatics had a surface area twice that of intralobular vessels. Stereological analysis was used to estimate the volume density of the components of the renal cortex. The volume density of lymphatics was found to be 0.0014, but because of the relative infrequency of lymphatics, this value was considered to be approximate. The volume density data for non-lymphatic renal components were found to be in close agreement with published data. From these volume density values it was concluded that the volume of cortical lymph in a functioning dog kidney is equivalent to about 1% of the volume of blood in the cortical peritubular capillaries.     

The intrarenal distribution of125I-albumin in the Syrian hamster

The intrarenal distribution of radioiodinated human serum albumin (125RISA) after intravenous injection was studied in Syrian hamsters by scintillation counting and frozen section autoradiography. After 15, 30 and 60 min the virtual plasma albumin space in the renal cortex of the hamster represented 6.49, 7.13, and 8.06 percent respectively of the kidney tissue volume. From the cortex to the renal papilla the albumin space increased to about 30 percent of the tissue volume. In comparison to this the albumin space in the renal cortex of the rat was about 20% and in the renal papilla about 33% (11). Frozen section autoradiography indicated that the distribution of radioalbumin in the renal cortex of the Syrian hamster is limited mainly to the kidney vessels, being especially noticeable in the glomerular capillaries. Toward the papilla increasingly greater (mainly extratubular) activity could be observed not only intravascularly but also interstitially. In the cortex of the rat kidney, on the other hand, radioactive albumin was accumulated (probably by filtration and reabsorption) predominantly in the proximal tubular epithelium. Wtithin 30 min thekidneys of the rat excreted mor than 10 times as much 125I than the hamster kidneys. These results (substantially less cortical accumulation and urinary excretion of radioalbumin in the Syrian hamster) indicate that, in contrast to the rat, obviously much less albumin is filtered (and then accumulated by proximal reabsorption) by the Syrian hamster glomeruli. This suggests that the Syrian hamster kidney is more suitable than the rat kidney for determining the interstitial, cortical, albumin space.     

Effects of renal nerve stimulation on intrarenal blood flow in rats with intact or inactivated NO synthases

AIM: We studied a possible action of nitric oxide (NO), an intrarenal vasodilator, to buffer a decrease in renal perfusion induced by electrical stimulation of renal nerves (RNS). METHODS: In anaesthetized rats RNS was performed (15 V, 2 ms pulse duration) for 10 s at the frequencies of 2, 3.5, 5 and 7.5 Hz. The total renal blood flow (RBF), an index of cortical perfusion, was measured using a Transonic probe on the renal artery. The outer and inner medullary blood flow (OMBF, IMBF) was measured by laser-Doppler flowmetry. The effect of RNS on RBF, OMBF and IMBF was determined in rats which were either untreated or pre-treated with L-NAME (0.6 or 1.8 mg kg(-1) i.v.), or S-methyl thiocitrulline (SMTC, 20 microg kg(-1) min(-1) i.v.), a selective inhibitor of neuronal NO synthase (nNOS). RESULTS: In untreated rats, RNS decreased IMBF significantly less than RBF and OMBF. High-dose L-NAME treatment significantly enhanced the RNS induced decrease of RBF but not of OMBF or IMBF. SMTC treatment significantly enhanced the decrease of IMBF, without affecting the response of RBF or OMBF. CONCLUSION: At intact NO synthesis the inner medullary circulation is not controlled by renal nerves to the extent observed for the outer medulla or cortex. NO generated by all NOS isoforms present in the kidney buffers partly the intrarenal vasoconstriction triggered by electrical RNS. The NO derived from nNOS seems of particular importance in the control of inner medullary perfusion, interacting with NO generated by endothelial NOS and renal nerves.     

The kidney of tapirs: a macroscopical study.

The renal cortex of tapirs, water-loving primordial ungulates, was continuous, nonlobed, and about 80% of renal mass in adult and 71% in term-neonate. In the neonates even the peripheral glomeruli were moderately mature. Tapirus bairdi had about 4 million glomeruli per kidney and T. pinchaque about 3 million smaller glomeruli. Number of glomeruli per gm of cortex was 12,444 in T. bairdi and 13,400 in T. pinchaque. Cortical loops were common in the medullary rays. The medulla was the simple crest-type. The terminal collecting ducts (T.C.D.) opened separately at the crest and not into a tubus maximus. The "outer stripe" of the outer medulla apparently was telescoped into the deep cortex. The medullary loops turned at a thick portion and at nearly all levels of the medulla. The medullary crest was lined by urothelium which extended into the ends of the T.C.D. Otherwise the T.C.D. were made of columnar epithelium. The pelvic urothelium was continuous with that of the medullary crest at the dorsal and ventral fornices. The fornices were well within the inner medulla. Hence only inner medulla could be exposed to pelvic urine. The hilar arteries, unlike the other two perissodactyl families (rhinoceri and equids), passed through the cortico-medullary (C-M) border and some large arteries and veins passed through the outer medulla to and from the C-M border without branches or tributaries. Unlike kidneys with a medullary crest in diverse eutherian mammals, tapirs lacked pelvic extensions along the major intrarenal blood vessels and thus lacked pelvic intervascular eminences.     

Renal Cortical Blood Redistribution after Bumetanide Related to Heterogenicity of Cortical Prostaglandin Metabolism in Dogs

Bumetanide is shown to increase renal blood flow and to augment the proportion of the cortical blood flow to middle cortex. This redistribution still takes place even when renal blood flow is maintained constant by renal artery clamping. Indomethacin pretreatment inhibits the increase of renal blood flow as well as the cortical blood redistribution. In vitro examinations of canine kidney tissue slices suggest that outer cortex and papilla are sites of prostaglandin synthesis. No differences in prostaglandin E degradation are observed within the cortex. This suggests a relative autonomy for prostaglandins in the outer cortex, whilst inner cortical areas are dependent on medullary/papillary prostaglandin E supply. The renal hemodynamic effect of bumetanide is therefore thought to be a result of a stimulation of mainly medullary/papillary prostaglandin synthesis.     

Mechanism of intrarenal blood flow redistribution after carotid artery occlusion.

Bilateral carotid artery occlusion results in an increase in mean arterial pressure, an increase in renal sympathetic nerve activity, and a redistribution of renal blood flow from inner to outer cortex. To elucidate the mechanism of the renal blood flow redistribution, carotid artery occlusion was performed in anesthetized dogs with the left kidney either having renal perfusion pressure maintained constant (aortic constriction) or having alpha-adrenergic receptor blockade (phenoxybenzamine); the right kidney of the same dog served to document the normal response. When renal perfusion pressure was maintained constant, renal blood flow distribution (microspheres) was unchanged by carotid artery occlusion. In the presence of renal alpha-adrenergic receptor blockade, carotid artery occlusion elicited the usual redistribution of renal blood flow from inner to outer cortex. The redistribution of renal blood flow observed after carotid artery occlusion is mediated by the increase in renal perfusion pressure rather than the increase in renal sympathetic nerve activity.