We have shown previously that a moderate reflex increase in renal sympathetic nerve activity (RSNA) elevated glomerular capillary pressure, whereas a more severe increase in RSNA decreased glomerular capillary pressure. This suggested that the nerves innervating the glomerular afferent and efferent arterioles could be selectively activated, allowing differential control of glomerular capillary pressure. A caveat to this conclusion was that intrarenal actions of neurally stimulated ANG II might have contributed to the increase in postglomerular resistance. This has now been investigated. Anesthetized rabbits were prepared for renal micropuncture and RSNA recording. One group (ANG II clamp) received an infusion of an angiotensin-converting enzyme inhibitor (enalaprilat, 2 mg/kg bolus plus 2 mg·kg−1·h−1) plus ANG II (∼20 ng·kg−1·min−1), the other vehicle. Measurements were made before (room air) and during 14% O2. Renal blood flow decreased less during ANG II clamp compared with vehicle [9 ± 1% vs. 20 ± 4%, interaction term (PGT) < 0.05], despite a similar increase in RSNA in response to 14% O2 in the two groups. Arterial pressure and glomerular filtration rate were unaffected by 14% O2 in both groups. Glomerular capillary pressure increased from 33 ± 1 to 37 ± 1 mmHg during ANG II clamp and from 33 ± 2 to 35 ± 1 mmHg in the vehicle group before and during 14% O2, respectively (PGT < 0.05). During ANG II clamp, postglomerular vascular resistance was still increased in response to RSNA during 14% O2, demonstrating that the action of the renal nerves on the postglomerular vasculature was independent of the renin-angiotensin system. This further supports our hypothesis that increases in RSNA can selectively control pre- and postglomerular vascular resistance and therefore glomerular ultrafiltration.
- renal innervation
- glomerular capillary pressure
- renal micropuncture
alterations in renal sympathetic nerve activity (RSNA) produce several effects on renal function that contribute to the kidneys main task of homeostatic regulation of body fluid balance. Previously, we have identified ultrastructurally two distinct nerve types that are differentially distributed to afferent and efferent arterioles (24, 25). Type I axons almost exclusively innervate the afferent arteriole, whereas type II axons are evenly distributed on both arterioles (25). Recently, we have shown that neuropeptide Y (NPY) is located in type II axon terminals but not type I axon terminals (23). Our findings are in accord with the study of Reinecke and Forssmann (38), who reported that the density of NPY-positive terminals was similar on the afferent and efferent arterioles (i.e., similar to type II axon distribution). Taken together, these findings implied that type I and II axons originated from different populations of neurons. On this basis, we hypothesized that different patterns of sympathetic outflow to the kidney may evoke selective changes in segmental renal vascular resistances. This concept of functionally specific populations of renal sympathetic nerves has also been addressed by other investigators (8, 9, 11, 15, 39, 40).
Previously, we have published micropuncture data compatible with selective neural control of pre- and postglomerular resistance (7). Graded increases in RSNA were reflexly induced via different levels of hypoxia. We demonstrated that 10% O2, which caused a severe increase in RSNA, increased both pre- and postglomerular resistance as reflected by the decrease in both renal blood flow (RBF) and glomerular filtration rate (GFR). However, 14% O2, which moderately increased RSNA, caused a predominant increase in postglomerular resistance and maintenance of GFR at a time when renal blood flow fell. These results provide evidence that different levels of reflexly induced increases in RSNA may differentially control pre- and postglomerular vascular resistances, compatible with selective activation of type I and II renal sympathetic nerves (7). A caveat to this conclusion was that, although in response to 14% O2 plasma renin activity was not increased (7), intrarenal actions of neurally stimulated ANG II may have been responsible for the increase in postglomerular resistance in response to 14% O2. This question has now been investigated.
In the present study, our hypothesis was that the increase in postglomerular resistance in response to a moderate reflex increase in RSNA was independent of the renin-angiotensin system. To test this hypothesis, the renin-angiotensin system was blocked by the administration of the angiotensin-converting enzyme (ACE) inhibitor enalaprilat, and blood pressure was restored to baseline by the simultaneous infusion of ANG II. Renal micropuncture studies were then performed before and during 14% O2, a stimulus previously shown to moderately increase RSNA and pre- and postglomerular resistance (7).
MATERIAL AND METHODS
Experiments were performed on male rabbits of a multicolored English strain (n = 14, mean body weight: 3.2 ± 0.2 kg, range: 2.6–3.7 kg). The experiments were performed in accordance with the Australian Code of Practice for the Care and Use of Animals for Scientific Purposes and were approved in advance by the Monash University Standing Committee on Ethics in Animal Experimentation.
Catheters were placed in the ear central arteries and marginal veins under local anaesthetic (xylocaine, Astra Pharmaceuticals; New South Wales, Australia). Conscious arterial pressure was measured for 20 min. Anesthesia was then induced by an intravenous administration of pentobarbitone sodium (90–150 mg plus 0.1–0.2 mg·kg−1·min−1 iv, Nembutal, Boehringer Ingelheim; New South Wales, Australia), and the rabbits were ventilated (model 683, Harvard). During surgery and throughout the experiment, fluid was infused intravenously at 0.17 ml·min−1·kg−1 [Hartmann's solution (compound sodium lactate), Baxter Healthcare; Toongabbie, New South Wales, Australia] to replace fluid losses. Surgery was performed on a heated table, and esophageal temperature was maintained at ∼37°C throughout the experiment via a servo-controlled infrared lamp (Digi-Sense Temperature Controller; Cole Palmer, IL). The rabbit was placed in an upright crouching position, and a left flank incision was made to expose the left kidney. Silastic catheters were inserted into both ureters, and the kidney was placed in a micropuncture cup. The renal nerves were identified, and a 3- to 5-mm length was freed from the surrounding tissue and carefully placed across a pair of hooked silver recording electrodes. The nerve and electrode were insulated using Wacker Sil-Gel (Wacker-Chemie; Munich, Germany). A transit-time flow probe was placed around the renal artery for measurement of RBF (2SB, Transonic Systems; Ithaca, NY). The kidney was then prepared for micropuncture (6).
After the completion of surgery, [3H]inulin (4 μCi bolus plus 300 nCi/ml, NEN Research Products) was added to the infusion of Hartmann's solution. After a 60-min equilibration period, the ventilation rate (tidal volume 14–18 ml/min, rate 30–50 breaths/min) was adjusted such that during the control period the arterial Po2 (PaO2) was between 90 and 110 mmHg. Each animal was randomly assigned to receive one of two treatments. One group (ANG II clamp) received an infusion of the ACE inhibitor enalaprilat (2 mg/kg bolus plus 2 mg·kg−1·h−1 iv, Merck, Sharpe & Dohme; Rahway, NJ) followed 5 min later by an infusion of ANG II (20 ng·kg−1·min−1 iv, human angiotensin, Sigma-Aldrich; St. Louis, MO) or vehicle (saline). These infusions were maintained throughout the experiment. A further 30-min equilibration period was allowed.
Measurements were made over three periods in each group: 30-min control (room air), 30-min 14% O2, and 10-min recovery (room air: 21% O2). There was a 20-min washout between periods. Each period consisted of a timed urine collection, with an arterial blood sample (2 ml) taken at the midpoint for clearance, blood gas, and hematocrit measurements. At the conclusion of the experiment, bolus doses of ANG I (10, 100, and 1,000 ng/kg iv, Auspep; Parkville, Victoria, Australia) were administered. The animal was then killed with an overdose of pentobarbitone (300 mg).
Mean arterial pressure (MAP) was measured by connecting the ear artery catheter to a pressure transducer (Cobe; Arvarda, CO), and the signal was amplified (model 7D, Grass Instruments; Quincey, MA). RSNA was amplified, filtered between 50 and 5,000 Hz, and full wave rectified and integrated using a low-pass filter with a time constant of 20 ms. The average voltage from the sympathetic neurogram over 2-s periods was defined as total RSNA. Changes in voltage of the signal above a user-defined threshold were classified as total RSNA discharge; in addition, the signal was separated into amplitude and frequency components as previously described (29).
Micropressure measurements were taken during the baseline and 14% O2 periods but not during the recovery period. In each period, three to six stop-flow (SFP), proximal tubular (PT), and peritubular capillary pressures (Pc) were taken in each period. Some rabbits used in this study (n = 4 rabbits/group) had glomeruli on the surface of the kidney; in these, glomerular capillary pressure (Pgc) was measured by direct capillary puncture (3/period) and estimated via SFP. Micropressures were measured using a servo-null pressure device (model 900A, Micropressure System, WPI).
MAP, heart rate, RBF, total RSNA, RSNA frequency, and RSNA amplitude were all continuously recorded and were sampled using an analog-to-digital data-acquisition card (Lab-PC+, National Instruments). Calibrated signals were displayed on screen and saved as 2-s averages as previously described (30).
Measurements and calculations.
MAP, heart rate, RBF, total RSNA, frequency of RSNA, and RSNA amplitude were averaged over each period. GFR was estimated via the clearance of [3H]inulin. Renal vascular resistance was calculated as MAP divided by RBF. Filtration fraction was calculated as GFR divided by renal plasma flow, calculated as RBF corrected for hematocrit. Urinary sodium concentrations were determined by flame photometry (model 943, Instrumentation laboratory; Milan, Italy). Plasma oncotic pressure (πa) was calculated from arterial plasma protein concentration (Ca) via a Lowry assay (6). Estimated Pgc was calculated as SFP + πa. Preglomerular resistance was estimated as (MAP − Pgc)/RBF, and postglomerular resistance was calculated as Pgc − Pc/(RBF − GFR). The pre-to-postglomerular resistance ratio was determined as the preglomerular resistance divided by the postglomerular resistance. The mean net filtration pressure (Puf) = Pgc − PT − πgc and the glomerular capillary ultrafiltration coefficient (Kf) = GFR/Puf, where πgc equals the mean glomerular oncotic pressure, calculated as πa + πe/2 (where πe is the efferent oncotic pressure). πe was derived from the efferent protein concentration, which was calculated as Ca/(1 − filtration fraction). However, Kf can only be calculated by the above formula if there is a net positive pressure at the efferent end of the glomerular capillaries (5).
Values are means ± SE. P ≤ 0.05 was considered to be statistically significant. A paired t-test was used to test for differences within a group in response to 14% O2. One-way repeated-measures ANOVA compared the response to 14% O2 between the groups, with factors group (PG; vehicle or ANG II clamp) and treatment (PT; before and after 14%O2). A significant change in the interaction term (PGT) indicated that the response to 14% O2 was different in the two groups.
Response to ANG II clamp.
Before the ANG II clamp infusions, conscious MAP was 82 ± 4 and 81 ± 2 mmHg and anesthetized MAP was 76 ± 3 and 74 ± 4 mmHg in the groups that would receive the ANG II clamp and vehicle infusions, respectively. In anesthetized rabbits, ACE inhibition caused a significant decrease in MAP (P = 0.02) and increase in RBF (P = 0.01); no changes were observed in the vehicle group (Fig. 1). The addition of ANG II to the ACE inhibition infusion returned MAP and RBF levels to those of the vehicle group (Fig. 1). No significant change in total RSNA was observed during the introduction of the ANG II clamp infusions (Fig. 1).
Baseline (room air).
No significant differences were observed in any variable between the vehicle and ANG II clamp groups during the baseline (room air, 21% O2) period (Figs. 2–4). These results demonstrated that the groups were under similar resting conditions before administration of the 14% O2 gas mixture.
Effect of ANG II clamp on responses to moderate hypoxia.
PaO2 during moderate hypoxia (14% O2) was not significantly different (PGT = 0.9; Fig. 2) between the ANG II clamp (50 ± 6 mmHg) and vehicle (45 ± 6 mmHg) groups, respectively. Total RSNA increased by 39 ± 13% and 37 ± 11%, which was not significantly different (PGT = 0.6; Fig. 2) in the ANG II clamp and vehicle groups, respectively. This increase in total RSNA was associated with a significant increase in the RSNA amplitude (19 ± 5% and 29 ± 10%, PGT = 0.4; Fig. 2) in the ANG II clamp and vehicle groups, respectively. No significant change in the frequency of RSNA was observed (1 ± 3% and 3 ± 7%, PGT = 0.8; Fig. 2). MAP (Fig. 2) and heart rate did not change significantly after moderate hypoxia.
Moderate hypoxia decreased RBF by 9 ± 1% and 21 ± 4% in the ANG II clamp and vehicle groups, respectively. The fall in RBF was significantly less in the ANG II clamp group (PGT = 0.04; Fig. 3). Renal vascular resistance increased by 9 ± 2% and 21 ± 4% in the ANG II clamp and vehicle groups, respectively. The rise in renal vascular resistance was significantly less in the ANGII clamp group (PGT = 0.05; Fig. 3). GFR did not change significantly in response to 14% O2 in either group (Fig. 3). However, the filtration fraction rose significantly from 15 ± 2 to 19 ± 4% (P = 0.03; Fig. 3) in response to moderate hypoxia during vehicle treatment but did not change in the ANG II clamp group (PGT = 0.2). No significant change in urine flow rate or urinary sodium excretion was seen in the ANG II clamp and vehicle groups in response to 14% O2.
In the ANG II clamp group, tubular SFP was 21 ± 1 mmHg during the baseline period and rose significantly to 25 ± 1 mmHg during 14% O2 (P = 0.01). In the vehicle group, tubular SFP was 22 ± 1 mmHg during the baseline period and rose significantly to 23 ± 1 mmHg during 14% O2 (P = 0.01). Ca was 4.1 ± 0.1 g% in both the ANG II clamp and vehicle groups during baseline and was not significantly effected by 14% O2 (PGT < 0.9). During 14% O2, estimated Pgc increased by 3.7 ± 0.9 and 2.0 ± 0.2 mmHg in the ANG II clamp and vehicle groups, respectively. The increase in estimated Pgc was significantly greater in the ANG II clamp group (PGT = 0.04; Fig. 4). Proximal tubule pressure was 11 ± 1 mmHg during baseline and 10 ± 1 mmHg during 14% O2 (P = 0.2) in the ANG II clamp group. Proximal tubule pressure was 10 ± 1 mmHg during baseline and 11 ± 1 mmHg during 14% O2 (P = 0.08) in the vehicle group. Estimated preglomerular resistance increased in response to moderate hypoxia by 2 ± 2% and 26 ± 8% in the ANG II clamp and vehicle groups, respectively. The rise in preglomerular resistance was significantly less in the ANG II clamp group (PGT = 0.01; Fig. 4). Estimated postglomerular resistance increased in response to moderate hypoxia by 28 ± 3% and 49 ± 7% in the ANG II clamp and vehicle groups, respectively. The rise in postglomerular resistance was not significantly different in the ANG II clamp and vehicle groups (PGT = 0.07; Fig. 4). The ratio of post- to preglomerular resistance in response to moderate hypoxia increased by 32 ± 4% and 20 ± 8% in the ANG II clamp and vehicle groups, respectively. The rise in the post-to-preglomerular resistance ratio was not significantly different between the two groups (PGT = 0.7; Fig. 4). The rabbits were all in a state of filtration disequilibrium (i.e., net positive pressure at the efferent end of the glomerular capillaries) in both periods of the experiments. Calculated Kf in response to moderate hypoxia fell by 36 ± 12% and 2 ± 9% in the ANG II clamp and vehicle groups, respectively. The fall in calculated Kf was significantly greater in the ANGII clamp group (PGT = 0.05).
Two-thirds of the rabbits used in this study had glomeruli visible on the surface of the kidney and therefore accessible to direct puncture. In the ANG II clamp group (n = 4), directly measured and SFP estimates of Pgc were 33 ± 1 and 33 ± 1 mmHg before and 37 ± 1 and 37 ± 1 mmHg after 14% O2, respectively. In the vehicle group (n = 4), directly measured and SFP estimates of Pgc were 33 ± 1 and 34 ± 1 mmHg before and 35 ± 1 and 36 ± 1 mmHg after 14% O2, respectively.
Recovery from hypoxia.
After the return to breathing room air, the rabbits were followed for 30 min; during the final 10 min of this period, measurements were taken. All variables, MAP, heart rate, PaO2, arterial Pco2, RSNA (total, frequency, or amplitude), renal vascular resistance, RBF, GFR, and filtration fraction had returned toward baseline values in both groups (Figs. 2 and 3).
Dose-response curves to ANG I.
At the end of the study, the peak MAP and RBF responses to bolus intravenous injections of ANG I were recorded. In the vehicle group, MAP increased by 7 ± 3, 34 ± 13, and 63 ± 16 mmHg and RBF decreased by 3 ± 3, 8 ± 2, and 37 ± 7 ml/min in response to 10, 100, and 1,000 ng/kg ANG I, respectively. In the ANG II clamp group, there was no detectable MAP or RBF response to even the highest dose of ANG I, demonstrating effective blockade of the conversion of ANG I to ANG II.
In response to hypoxia, peripheral chemoreceptors are activated and via central pathways a reflex increase in RSNA is induced, as we and others (7, 21, 27, 30, 35) have previously observed (18, 34, 35). Previously, we have demonstrated an increase in RSNA and a fall in RBF (∼25%) but maintenance of GFR in response to 14% O2 (7, 21, 27, 30, 35). These responses to hypoxia are due to a reflex increase in RSNA because they are abolished by renal denervation (7, 21, 27, 30, 35). Renal micropuncture demonstrated that GFR was maintained by an increase in Pgc caused by a predominant increase in postglomerular resistance (7). The present study confirmed this finding. Whether this action on the postglomerular vessels was a direct action of the nerves or an indirect effect mediated by neurally stimulated renin release remained an important unanswered question that was the focus of the present study.
In the ANG II clamp group, the increase in renal vascular resistance in response to moderate hypoxia was attenuated but not abolished. The neurally mediated release of renin was therefore partly, but not entirely, responsible for the increase in renal vascular resistance in response to a reflex increase in RSNA. Analysis of the segmental vascular resistance changes in response to 14% O2 in the ANG II clamp group demonstrated that the remaining increase in renal vascular resistance was due to an increase in postglomerular not preglomerular vascular resistance. The increase in postglomerular resistance was not significantly different between the groups. Therefore, the increase in postglomerular resistance in response to a moderate reflex increase in RSNA was independent of the renin-angiotensin system. In comparison, electrical stimulation of the renal nerves (activating all renal nerves) causes a predominant increase in preglomerular resistance (19, 37, 42), compatible with the greater innervation density of the afferent compared with the efferent arteriole (2, 25). During ANG II inhibition, the vasoconstrictor response to electrical renal nerve stimulation was of a lesser magnitude but still predominantly preglomerular (37). Reflex activation of the renal nerves in response to moderate hypoxia therefore results in a markedly different response to that seen in response to electrical stimulation of the renal nerves.
Previously, we have identified two types of axons innervating the renal arterioles, with type II axons being equally distributed on afferent and efferent arterioles and also present on renin granular cells (24, 25). The present study demonstrates a response to a moderate level of reflex activation of the renal nerves that is compatible with selective activation of type II nerves. This study also suggests that type I axons, which almost exclusively innervate the afferent arterioles, are not activated in response to moderate hypoxia, although we have shown a type I response, that of an intense increase in preglomerular resistance, in response to a greater increase in RSNA elicited by more severe hypoxia previously (7). Therefore, our data support our hypothesis that the nerves innervating the renal arterioles can be selectively activated. Our results are perhaps only applicable to cortical but not juxtamedullary glomeruli. We have previously demonstrated that medullary blood flow, derived from juxtamedullary efferent arterioles, is relatively insensitive to reflex activation of the renal nerves via hypoxia (21).
Indirect support for our hypothesis comes from other studies in which whole kidney responses to reflex activation of RSNA have been examined. Several studies in response to a reflex increase in RSNA have documented decreases in RBF without changes in GFR, suggesting a predominant increase in postglomerular resistance (14, 28, 30, 36). However, our studies are the only studies to simultaneously record RSNA and measure changes in Pgc using renal micropuncture techniques. Such measurements are essential in determining the relative contribution of the pre- and postglomerular vasculature to resistance changes within the kidney.
Perhaps surprisingly, the increase observed in preglomerular resistance in the vehicle group in response to 14% O2 was abolished by the ANG II clamp. This suggests that neurally stimulated renin is acting principally at the site of the afferent arteriole. Certainly, this is in accord with studies demonstrating that afferent arterioles do indeed constrict in response to ANG II (see Ref. 33). In our earlier study, plasma renin activity was not increased by 14% O2 (7), but our present study indicates that renin release was stimulated locally and acting on the preglomerular vasculature. This coincides with the evidence demonstrating that high concentrations of renin are present in the periarterial interstitium surrounding the afferent arteriole (32). Perhaps in consequence of this lack of preglomerular constriction, a decrease in Kf in the ANG II clamp group in response to hypoxia was observed. The glomerular capillaries are not innervated, and therefore this is not likely to be a direct effect of the increase in RSNA (25). The most likely explanation for this decrease in Kf in the ANG II clamp group is that the glomerular podocytes have contracted to counter the increase in Pgc, brought about by the predominant increase in postglomerular resistance, as previously suggested (20).
A limitation of our study was that tubular SFPs were used to estimate Pgc. This method has been shown in some studies to lead to small overestimations of Pgc due to interruption of the tubuloglomerular feedback mechanism (1). It is also possible that such an effect may have been of greater magnitude in the ANG II clamp group because ANG II enhances the sensitivity of the tubuloglomerular feedback response (31). However, the rabbits used in these studies commonly have glomeruli visible on the surface of the kidney (6). Therefore, in two-thirds of the rabbits in both groups, it was possible to compare SFP estimates and direct capillary measurements of Pgc. In those animals, directly measured Pgc increased in response to reflex activation of RSNA via 14% O2 in both vehicle and ANG II clamp groups, very similar results to those observed with SFP estimates.
Previously, we have demonstrated on several occasions that the renal hemodynamic response to 14% and 10% O2 was completely abolished after renal denervation, including changes in RBF, GFR, and thus filtration fraction (21, 27, 30). These results suggest that the pre-to-postglomerular resistance ratio has not changed. However, a differential effect of hypoxia on pre- to postglomerular vascular resistance cannot completely rule out. Because previous studies have demonstrated direct actions of hypoxia on afferent arterioles in vitro (22), substantial differences in the calcium receptor subtype on the afferent and efferent arterioles (12) raised the possibility that hypoxia may influence nitric oxide production (41), with evidence suggesting that nitric oxide may differentially effect pre- and postglomerular vascular resistance (17). However, such a caveat does not detract form our conclusion that ANG II is not responsible for the predominant increase in postglomerular resistance in response to 14% O2.
In this study, the renin-angiotensin system blocked by the infusion of an ACE inhibitor, causing blood pressure to fall by 10–20 mmHg. MAP was restored to baseline by the infusion of ANG II. This was achieved as blood pressure in the ANG II clamp and vehicle groups was not statistically different; fortuitously, RBF was also not significantly different. This approach was chosen rather than the administration of an AT1 receptor blocker to avoid the confounding effect of differences in blood pressure between the groups. However, other possible actions of the ANG II and enalaprilat infusions should also be considered. It is well known that ANG II can act centrally to increase RSNA (16), an action that might potentially confound the interpretation of this study. It has also been recently suggested that ANG II directly activates postganglionic neurons (26). However, in our study, the ANG II infusion did not alter baseline RSNA (Figs. 1 and 2) and the increase in RSNA in response to 14% O2 was the comparable in both vehicle and ANG II clamp groups. Thus the remaining increase in postglomerular resistance in the ANG II clamp group was not due to a relatively greater increase in RSNA in response to 14% O2. A consequence of administration of the ACE inhibitor enalaprilat is that there may have been an accumulation of the vasodilator bradykinin, which might have affected renal function. However, it has been previously shown that RBF and sodium excretion were unaffected by a bradykinin receptor antagonist in rabbits pretreated with vehicle or captopril (4).
The idea that subpopulations of neurons innervating a given organ may be able to selectively control a particular function of that tissue is not new (13). Such subpopulations of nerves have been demonstrated previously in the gut (13) and eye (3), although such a possibility in the kidney has received little attention until the last decade (8, 9, 11, 15, 39, 40). It has generally been accepted that the stimulation of the renal nerves produces frequency-dependent decreases in renal function (see Ref. 10). However, afferent glomerular arterioles of the kidney are three times more densely innervated than the efferent glomerular arterioles (2, 25). Therefore, not surprisingly, electrical stimulation of the renal nerves at supramaximal voltages predominantly increases preglomerular vascular resistance and decreases glomerular filtration rate (see Ref. 10). However, in this and our earlier study (7), we have seen a very different situation whereby reflex increases in RSNA induced via hypoxia can selectively control pre- and postglomerular vascular resistance and therefore glomerular ultrafiltration. This has important implications for understanding the reflex control of body fluid balance and for diseases in which renal nerve activity is increased, because increased activity of the different subpopulations of renal nerves would produce quite different effects.
In conclusion, during blockade of the renin-angiotensin system, an increase in reflex RSNA caused a predominant increase in postglomerular resistance compatible with our main hypothesis of the kidney being innervated by different populations of renal sympathetic nerves that can be selectively activated to differentially affect pre- and postglomerular resistance to regulate glomerular ultrafiltration.
This study was supported by National Health and Medical Research Council of Australia Grant 236821. K. M. Denton was a recipient of a Research Fellowship awarded by the Foundation for High Blood Pressure Research, Australia.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Copyright © 2004 the American Physiological Society