Renal Arterial Perfusion Pressure Research Articles

The role of the kidney in regulating arterial blood pressure

The kidney plays a central role in the regulation of arterial blood pressure. A large body of experimental and physiological evidence indicates that renal control of extracellular volume and renal perfusion pressure are closely involved in maintaining the arterial circulation and blood pressure. Renal artery perfusion pressure directly regulates sodium excretion-a process known as pressure natriuresis-and influences the activity of various vasoactive systems such as the renin-angiotensin-aldosterone system. As a result, many researchers argue that identifying any marked rise in blood pressure requires resetting of the relationship between arterial blood pressure and urinary sodium excretion, which can occur by an array of systemic or local mechanisms. Almost all of the monogenic forms of hypertension affect sites in the kidney associated with sodium handling and transport. Experimental models of spontaneous hypertension, such as the Dahl salt-sensitive rat, have been used to study the effects of kidney transplantation on blood pressure. Results from studies of kidney transplantation indicate that pressure sensitivity to sodium intake 'follows' the kidney, meaning that the recipient of a 'salt-resistant kidney' acquires sodium resistance, and that the recipient of a 'salt-sensitive kidney' acquires pressure sensitivity. The examples above and discussed in this Review demonstrate that it should come as no surprise that most disorders that affect the kidney or the renal vasculature commonly lead to secondary forms of hypertension.

Identification of Novel Endogenous Cytochrome P450 Arachidonate Metabolites with High Affinity for Cannabinoid Receptors

Arachidonic acid is an essential constituent of cell membranes that is esterified to the sn-2-position of glycerophospholipids and is released from selected lipid pools by phospholipase cleavage. The released arachidonic acid can be metabolized by three enzymatic pathways: the cyclooxygenase pathway forming prostaglandins and thromboxanes, the lipoxygenase pathway generating leukotrienes and lipoxins, and the cytochrome P450 (cP450) pathway producing epoxyeicosatrienoic acids and hydroxyeicosatetraenoic acids. The present study describes a novel group of cP450 epoxygenase-dependent metabolites of arachidonic acid, termed 2-epoxyeicosatrienoylglycerols (2-EG), including two regioisomers, 2-(11,12-epoxyeicosatrienoyl)glycerol (2-11,12-EG) and 2-(14,15-epoxyeicosatrienoyl)glycerol (2-14,15-EG), which are both produced in the kidney and spleen, whereas 2-11,12-EG is also detected in the brain. Both 2-11,12-EG and 2-14,15-EG activated the two cannabinoid (CB) receptor subtypes, CB1 and CB2, with high affinity and elicited biological responses in cultured cells expressing CB receptors and in intact animals. In contrast, the parental arachidonic acid and epoxyeicosatrienoic acids failed to activate CB1 or CB2 receptors. Thus, these cP450 epoxygenase-dependent metabolites are a novel class of endogenously produced, biologically active lipid mediators with the characteristics of endocannabinoids. This is the first evidence of a cytochrome P450-dependent arachidonate metabolite that can activate G-protein-coupled cell membrane receptors and suggests a functional link between the cytochrome P450 enzyme system and the endocannabinoid system.

Putting the Brakes on Renin Release

Modulation of renin release from juxtaglomerular cells is critical for appropriate adjustments of the cardiovascular and renal systems to internal and external stresses, and dysregulation of renin release participates in the pathophysiology of hypertension, vascular disease, heart failure, and chronic renal disease. This justifies investments in research to elucidate the fundamental mechanisms regulating renin release. These investments have yielded, and continue to yield, high returns, as exemplified by Schweda et al1 in this issue of Hypertension , showing that A1 receptors mediate high perfusion pressure–induced inhibition of renin release, whereas prostaglandins (PGs) participate in low perfusion pressure–mediated stimulation of renin release. The purpose of this commentary is to discuss how Schweda et al’s findings confirm and challenge present-day models of renin release. As comprehensively reviewed by Davis and Freeman2 and Keeton and Campbell,3 investigators recognized early on that three systems, namely the sympathetic nervous system, the macula densa apparatus, and the intrarenal baroreceptor, are the primary physiological mechanisms regulating renin release from juxtaglomerular cells. A key development was the recognition that the two most important biochemical accelerators of renin release are catecholamines (mediating sympathetically induced renin release) and PGI2 (mediating macula densa–induced and intrarenal baroreceptor–stimulated renin release).4 Subsequently, a third autocoid, adenosine (acting via A1 receptors), was proposed to serve as a molecular brake on renin release and thereby to moderate the effects of catecholamines and PGI2 on renin secretion.5 Because cAMP is a critical second messenger mediating the exocytosis of renin from juxtaglomerular cells, adenylyl cyclase unifies these concepts because β-adrenoceptors and PGI2 receptors accelerate, whereas A1 receptors brake the rate of cAMP production. The results reported by Schweda et al corroborate the accelerator/brake model of renin release because they report that PGs mediate stimulation of renin release …

Isolated rat kidney perfused with dextran and bovine serum albumin: A stable model for investigating renal drug handling

Introduction: The rat isolated perfused kidney (IPK) preparation is a very useful model for pharmacokinetic and pharmacologic studies. Bovine serum albumin (BSA) is the oncotic agent used most commonly in IPK models, but the protein is expensive and varies significantly in quality. The present study evaluated the use of dextran to replace a large proportion of BSA as the oncotic agent, to establish a more reliable and economic IPK model for pharmacokinetic studies. Methods: The right kidneys of male Sprague–Dawley rats were isolated and perfused in recirculating mode with Krebs–Henseleit pH 7.4 buffer containing amino acids, glucose and 65 g/l BSA (BSA group, n=11) or 6.5 g/l BSA plus 36 g/l dextran (dextran/BSA group, n=6). 14C-Inulin was added to the perfusate to permit estimation of glomerular filtration rate (GFR). An antiviral guanosine analogue, AM188, was administered to the IPK perfusate to investigate its renal disposition. During the 130-min experimental period, urine was collected in 10-min intervals and perfusate was collected at the midpoint of these intervals. Results: The kidney functional parameters were generally better and more stable in the dextran/BSA IPKs when compared to the BSA group. At a similar perfusate flow rate, the IPKs in the dextran/BSA group exhibited lower renal artery perfusion pressure, a higher GFR, and more extensive tubular reabsorption of water, glucose, and sodium. These functional parameters were acceptable and stable throughout the whole experimental period in the dextran/BSA group. The renal clearance of AM188 was higher in the dextran/BSA group compared with that in the BSA group. Discussion: Using a large proportion of dextran and a small proportion of BSA as oncotic agent in perfusate provides an improved IPK preparation. This offers a reliable and economic rat IPK model for pharmacokinetic studies.

Effects of osmotic agents for cold kidney preservation

The beneficial effect of UW solution may result from its ability to prevent tissue edema during cold storage. This study was conducted to determine which impermeant was effective in this regard during cold storage of a rat kidney in solution. Functional and morphological studies were made on a rat isolated perfused kidney (IPK) following 24 hour-cold storage in various tested solutions. Right nephrectomy was performed in 95 male rats by the method of Nishitsutsuji-Uwo et al and the kidney was perfused and stored at 4 degrees C for 24 hours as follows: glucose (194 mM) as a control, mannitol, sucrose, raffinose (140 mM in each), lactobionate (100 mM), raff + lact, hydroxyethyl starch 20, 40 (5%) with electrolyte composition essentially the same as that of Euro-Collins or UW solution. Kidneys stored for 24 hrs at 4 degrees C were perfused by the IPK apparatus. The perfusate flow rate was adjusted to maintain the renal arterial perfusion pressure at 100 mmHg. Raff, raff + lact or UW solution showed significantly higher fractional reabsorption of sodium than the control with no change in renal hemodynamics. The release of LDH into the perfusate was significantly less in raffinose than the control. Raffinose may thus be considered to function effectively as an impermeant for cold kidney preservation and molecule size would appear more important than negative charge for rat kidney preservation.

Renal vasodepressor mechanisms

Renal vasodepressor hormone: Medullipin I is the renomedullary vasodepressor hormone secreted by the renomedullary interstitial cells of the renal papilla. It is conveyed to the liver where it is converted to its active form, medullipin II. Medullipin II is a vasodilator that suppresses sympathetic tone and causes diuresis and natriuresis. Its actions are opposite to those of angiotensin II. These are feedback control systems. The secretion and conversion of medullipin is related to the cytochrome P-450 dependent enzyme system of kidney and liver. Deficiency of medullipin: A deficiency of medullipin is considered to contribute to the pathogenesis of various hypertensive states. There are three known causes for such a deficiency, (1) removal of renomedullary interstitial cells by bilateral nephrectomy, renal surgical papillectomy, chemical papillectomy, papillary atrophy or necrosis; (2) decrease in number and damage to renomedullary interstitial cells in accelerated experimental hypertension and malignant hypertension of humans; and (3) dysfunction of renomedullary interstitial cells as mediated by angiotensin II, by resetting of the effect of increased renal artery perfusion pressure, by stimulation of the renal sympathetic nerve, by inhibition of nitric oxide synthesis and possibly by inhibition of cyclo-oxygenase. Secretion of Medullipin I: The main factor influencing secretion of medullipin I by the kidney appears to be the renal artery perfusion pressure. Elevation of this pressure is attenuated by the presence of medullipin I in the renal venous effluent. Lowering the pressure below normal shuts off this secretion. This is opposite to the effects of perfusion pressure on renin secretion, as elevation shuts off renin secretion while depression turns it on.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced Renal Arterial Perfusion Pressure Stimulates Renin Release from Domestic Fowl Kidneys

Systemic hypovolemia and hypotension increase plasma renin activity (PRA) in fowl, but it is not clear whether this response is mediated directly by reduced renal arterial perfusion pressure (RAPP) or indirectly via renal nerves activated when systemic baroreceptors detect hypotension. To evaluate the influence of RAPP on renin release, arterial and renal venous blood samples were collected as RAPP was reduced step-wise from 108 mm Hg (control) to 71 and 47 mm Hg. PRA in systemic arterial (aPRA) and renal venous (vPRA) plasma was measured as the rate of fowl angiotensin 1 (ANG I) generation. Basal vPRA (2.47 ± 0.6 ng × ml -1 × min -1) tended to be higher than aPRA (1.24 × 0.3 ng × ml -1 × min -1). When RAPP was reduced to 47 mm Hg both vPRA (4.35 × 0.6 ng × ml -t × min -1) and aPRA (1.91 ± 0.3 ng × ml -1 × min -1) increased significantly. Significant negative slopes ( P = 0.01) were obtained when changes in aPRA or vPRA were regressed on RAPP. Mean systemic arterial pressure did not change during reductions in RAPP, nor did angiotensinogen concentrations differ when systemic arterial (472 ± 30 ng/ml) and renal venous (460 ± 27 ng/ml) plasma values were compared. Renal plasma flow was fully autoregulated as RAPP was reduced from 108 to 47 mm Hg; consequently, RAPP-induced increases in vPRA cannot be attributed to hemoconcentration of secreted renin. These results demonstrate that reductions in RAPP directly stimulate renin release from domestic fowl kidneys.

Response of the avian kidney to acute changes in arterial perfusion pressure and portal blood supply.

Domestic fowl kidneys autoregulate total renal blood flow and glomerular filtration rate (GFR) over a wide range of renal arterial perfusion pressure (RAPP). Sustained (approximately 2-4 h) restriction of renal portal blood flow attenuates the autoregulatory responses. The present study was designed to assess the effects of acute (approximately 10 min) alterations of renal portal blood flow on renal function, and to dissociate the renal responses to altered renal portal blood flow from the renal responses to reductions in RAPP. The thermal pulse decay (TPD) technique and p-aminohippuric acid clearance (CPAH) were used to measure blood flow. During acute increases and decreases in renal portal blood flow, regional renal blood flow as measured by the TPD system (RBFTPD) was significantly positively correlated with total kidney blood flow represented by CPAH (RBFPAH). These results indicate that changes in total kidney blood flow induced by alteration of portal perfusion were reflected in the regional measurement of renal blood flow. Changes in renal portal blood flow did not affect the urine flow rate (UFR), GFR, or fractional excretion of sodium (FENa). Reducing RAPP from 120 to 50 mmHg significantly reduced UFR, GFR, and FENa. Overall, these results indicate that large acute changes in renal portal blood flow can significantly alter total renal blood flow without significantly affecting parameters (UFR, GFR, and FENa) primarily influenced by the renal arterial vasculature.

Use of a thermal pulse decay system to assess avian renal blood flow during reduced renal arterial perfusion pressure

Using a simplified avian kidney model, renal arterial perfusion pressure (RAPP) was reduced from 120 (control) to 70 mmHg (near the glomerular filtration rate autoregulatory limit) and then to 46 mmHg (below the glomerular filtration rate autoregulatory range) in kidneys with ambient or partially restricted renal portal flow. Renal blood flow (RBF) was measured with a thermal pulse decay (TPD) system, using TPD thermistor probes inserted at three locations to evaluate regional differences in RBF. The clearance (CPAH) and extraction of p-aminohippuric acid were used to calculate renal plasma flow (RPF). CPAH, RPF, and RBF values were consistently lower for kidneys with restricted portal flow than for kidneys with ambient portal flow. Reducing RAPP to 46 mmHg did not significantly reduce CPAH, RPF, or RBF in the ambient group but did significantly reduce CPAH and RPF (regressed on RAPP) in the restricted group. RBF was not significantly affected when RAPP was reduced in the restricted group, although significant regional differences in blood flow were recorded. Renal vascular resistance decreased significantly as RAPP was reduced to 46 mmHg in the ambient group, confirming the renal autoregulatory response. In separate validation studies, significant reductions in RBF were detected by the TPD system during acute obstructions of portal and/or arterial flow. Overall, the results support previous evidence that avian RBF remains constant over a wide range of RAPPs. Observations of nonuniform intrarenal distributions of portal blood flow suggest that the portal system maintains the constancy of RBF in regions with proportionately high portal-to-arterial flow ratios.

Autoregulation of avian renal plasma flow: contribution of the renal portal system

A simplified avian kidney model was used to assess renal plasma flow (RPF) at normal (100–110 mmHg) or unilaterally reduced (40–50 mmHg) renal arterial perfusion pressure (RAPP) in domestic fowl with ambient (AMBIENT group) or restricted (RESTRICTED group) renal portal flow. Direct measurement of para-aminohippuric acid (PAH) extraction efficiencies (EPAH) allowed avian RPF to be calculated from the clearance of PAH (CPAH). EPAH was unaffected by RAPP, thereby validating the use of PAH to estimate RPF during experimental hemodynamic manipulations. CPAH and RPF were unaffected by RAPP in the AMBIENT group (“perfect” autoregulation), but decreased significantly compared with contralateral kidney values during reduction of RAPP in the RESTRICTED group. Urine flow and glomerular filtration rates (GFR) were reduced unilaterally along with RAPP, regardless of the portal perfusion status. The renal portal system contributes to overall RPF autoregulation in domestic fowl, helping to maintain constancy of renal blood flow even after RAPP is reduced well below the GFR autoregulatory limit.

SECRETION OF MEDULLIPIN I BY ISOLATED KIDNEYS PERFUSED UNDER ELEVATED PRESSURE

1. Medullipin I (Med I) is a hormone extracted from renal papillae and its renomedullary interstitial cells (RIC). Med I is stimulated by elevation of the renal artery perfusion pressure. 2. When isolated normal rat kidneys were perfused either with oxygenated blood or with 5% albumin bubbled with O2 at elevated perfusion pressures, Med I appeared to be secreted into the renal venous effluent (RVE). Addition of Tween 20, treatment of the assay rat with SKF 525A, inhibitor of cytochrome P-450 and removal of the liver from the systemic circulation prevented vasodepression of both the RVE and extracted Med I. The lipid in the RVE gave the same dose-response as extracted Med I. 3. Lowering the renal artery perfusion pressure below normal inhibited the secretion of Med I. As the perfusion pressure was elevated Med I secretion appeared to increase. 4. Previous observations and the present study support the view that the renin-angiotensin system and the Medullipin system are double feedback systems involved in blood pressure control.

Afferent arteriolar responsiveness to altered perfusion pressure in renal hypertension.

The present study was performed to determine the role of afferent arterioles in the impaired autoregulatory response shown to occur in the contralateral kidney of Goldblatt hypertensive rats. The responsiveness of juxtamedullary afferent arterioles to alterations in perfusion pressure was studied in the nonclipped kidney of two-kidney, one clip hypertensive and sham-operated rats. Systolic pressure, 5-6 weeks after clipping, averaged 184 +/- 6 mm Hg in the hypertensive rats (n = 16) and 121 +/- 3 mm Hg in the sham-operated control rats (n = 7). By using the in vitro blood-perfused juxtamedullary nephron technique, afferent arterioles were directly visualized, and their inside diameters were measured by videomicroscopic methods. In sham-operated kidneys perfused with blood from normotensive rats, afferent arteriolar diameter averaged 22.8 +/- 1.8 microns at a renal arterial perfusion pressure of 151 +/- 1 mm Hg and increased to 24.8 +/- 1.8 microns when perfusion pressure was reduced to 110 +/- 2 mm Hg. Conversely, in hypertensive kidneys perfused with blood from either hypertensive or normotensive rats, the afferent arterioles failed to vasodilate and actually exhibited a slight decrease in diameter from 24.6 +/- 1.3 to 23.0 +/- 2.3 microns in response to the same reduction in perfusion pressure. Vasodilator capability, however, could be demonstrated in response to verapamil and sodium nitroprusside, which increased afferent diameter in both the sham-operated and hypertensive groups of rats. Thus, unlike arterioles from normotensive rats, juxtamedullary afferent arterioles from two-kidney, one clip Goldblatt hypertensive rats fail to vasodilate after a reduction in perfusion pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary sodium, glomerular filtration rate autoregulation, and glomerular size distribution profiles in domestic fowl (Gallus gallus)

Mammalian glomerular filtration rate (GFR) autoregulation can be impaired by protocols that inhibit tubuloglomrular feedback, such as high sodium intake. Domestic fowl were fed diets containing either high sodium (0.39% Na: High-Na Group) or low sodium (0.03% Na: Low-Na Group). An arterial snare was used to reduce renal arterial perfusion pressure (RAPP) in a stepwise fashion to evaluate GFR autoregulation. Absolute sodium excretion, fractional sodium excretion (FENa), and ambient systemic arterial blood pressure were significantly elevated in the High-Na Group when compared with the Low-Na Group, and pressure natriuresis was abolished by the Low-Na diet. However, GFR autoregulatory profiles were identical in birds fed High-Na and Low-Na diets, suggesting that tubuloglomerular feed-back does not contribute significantly to avian GFR autoregulation. Filtering glomeruli were stained in vivo with alcian blue dye to determine if RAPP-induced reductions in GFR are associated with cessation of filtration (glomerular intermittency) by a portion of the nephron population. RAPP was held below the GFR autoregulatory range (experimental group) or was at ambient systemic arterial pressure (control group) during glomerular staining. Reducing RAPP below the autoregulatory range reduced GFR by 50%, but similar glomerular size distribution profiles were observed for experimental and control groups. These results indicate that sustained glomerular intermittency does not contribute to the decrease in GFR when RAPP is reduced below the autoregulatory range.

Resetting of the pressure range for blood flow autoregulation in the rat kidney

Both a myogenic response and the tubuloglomerular feedback control mechanism seem to be involved in autoregulation of glomerular filtration rate (GFR) and renal blood flow (RBF). Earlier experiments have shown that clamping of renal arterial perfusion pressure, below the autoregulatory range, reduces single-nephron GFR, and that this low value is maintained during the first 10-15 min after release of the clamp. It was also found that the tubuloglomerular feedback mechanism in the early declamp phase was strongly activated to reduce GFR. These findings can not be easily understood with the current knowledge of autoregulation, but would suggest a resetting of RBF and GFR autoregulation to a new level. To test this, left renal arterial perfusion pressure was reduced from 100 to 60 mmHg during 20 min with and without angiotensin converting enzyme inhibition (0.5 mg i.v. enalapril). Renal blood flow was measured with laser-Doppler flowmetry. When arterial perfusion pressure was reduced from 100 to 60 mmHg for 20 min, RBF was reduced to 77% of control and remained at this low level during the first minutes of declamp. In this situation there was an autoregulation to a new level. Renal blood flow was then slowly normalized (16.1 min). In the enalapril-treated animals RBF was only reduced to 85% during the 20 min of clamping and returned immediately to the control level at declamp. Thus, these experiments demonstrate that if renal blood flow is decreased by reducing the perfusion pressure below the normal autoregulatory range the pressure range for blood flow autoregulation resets to a lower level and that this change is mediated via the renin-angiotensin system.

Tubuloglomerular feedback responses during peritubular infusions of calcium channel blockers

Experiments were performed in pentobarbital-anesthetized rats to evaluate the dependence of the effector limb of the tubuloglomerular feedback mechanism on transmembrane calcium flux through potential-operated calcium channels. Peritubular capillary infusions of the calcium channel blockers, verapamil and nifedipine, were used to achieve high intrarenal levels without influencing arterial blood pressure. Proximal tubule stop-flow pressure (SFP) and single-nephron glomerular filtration rate (SNGFR) tubuloglomerular feedback responses were obtained during control conditions and during simultaneous peritubular capillary infusion with an isotonic saline solution containing either verapamil or nifedipine. Infusion of either 10(-3) M verapamil or 10(-3) M nifedipine, at a rate of 20 nl/min, increased resting SFP (measured during conditions of zero distal volume delivery) and markedly attenuated both the SFP and SNGFR feedback responses to a late proximal perfusion rate of 30 nl/min. Infusion of verapamil (10(-3) M) also increased the slope of the relationship between SFP and renal arterial perfusion pressure between 80 and 120 mmHg (0.43 +/- 0.03 vs 0.24 +/- 0.02, P less than 0.001, n = 10). These findings support the hypothesis that the preglomerular contractile elements responsive to signals from the macula densa cells are activated by calcium influx through potential-operated calcium channels. Furthermore, the preglomerular contractile elements sensitive to calcium channel blockers can dilate further even when orthograde flow to a single macula densa segment is interrupted.

Arterial pressure effects on preglomerular microvasculature of juxtamedullary nephrons

Videomicroscopic and micropuncture techniques were utilized to determine segmental microvascular responses of in vitro blood-perfused juxtamedullary nephrons to step changes in renal arterial perfusion pressure (PP). At a PP of 104 +/- 2 mmHg, inside diameters of arcuate arteries (ARC), interlobular arteries (ILA), and afferent arterioles (AFF) averaged 68.6 +/- 6.4, 35.7 +/- 1.5, and 20.4 +/- 2.3 microns, respectively. Variations in PP within the range of 70-180 mmHg elicited alterations in microvessel diameters with the following slopes: ARC, -0.15 micron/mmHg; ILA, -0.13 micron/mmHg; and AFF, -0.14 micron/mmHg. In other experiments, intravascular pressures were measured during changes in PP. Glomerular capillary pressure was well regulated (slope = 0.19 +/- 0.03 mmHg/mmHg), and mid-AFF pressure was partially regulated (slope = 0.60 +/- 0.17 mmHg/mmHg); however, pressure measured at the ILA-AFF branch point responded passively to changes in PP (slope = 0.95 +/- 0.06 mmHg/mmHg). These observations reveal that, although the entire preglomerular vasculature of juxtamedullary nephrons is capable of actively responding to changes in PP, afferent arterioles are responsible for the predominant resistance adjustment throughout the normal autoregulatory range.

4 Control of blood and extracellular volume

Blood and extracellular fluid volume are maintained within narrow limits despite considerable daily variations in the intake in salt and water. As summarized schematically in Figure 15, the urinary excretion of salt and water responds to changes in blood volume and arterial pressure. Volume-sensitive receptors located predominantly in the cardiac atria and arterial tree sense acute changes in the filling of the blood volume compartment, and urinary sodium excretion is adjusted in response to these detector mechanisms by virtue of alterations in both glomerular filtration rate and tubular sodium reabsorption. The reabsorption of sodium by the tubule responds to changes in extracellular fluid volume as well as to changes in filtered sodium load. Glomerular filtration rate and tubular reabsorption of sodium are influenced importantly by physical properties of the plasma in glomerular and peritubular capillaries and by the composition of the tubular fluid. The renal arterial perfusion pressure is a major factor regulating tubular reabsorption of sodium and water as signalled via changes in renal interstitial hydrostatic fluid pressure. Renal nerves and a variety of systemic and local hormones also influence tubular reabsorption of sodium and water directly by effects on transepithelial sodium transport and/or indirectly by altering renal medullary haemodynamics and the pressure-natriuresis-diuresis relationships. Thus, utilizing a variety of overlapping effector mechanisms that influence renal sodium and water excretion, mammalian organisms have achieved a high degree of stability of body fluid volumes. The fundamental relationship between arterial pressure and renal excretion appears to be the major mechanism which provides for the long-term control of body fluid volume. The sensitivity of the pressure-natriuresis-diuresis relationship is modified by the efferent pathways of the rapid-acting reflex and mechanoreceptor detectors of volume. Working together, these mechanisms provide a remarkable degree of rapid and long-term extracellular and blood volume stability.

Model for evaluating avian renal hemodynamics and glomerular filtration rate autoregulation.

Multiple vascular connections in normal avian kidneys make it difficult to experimentally manipulate renal blood flow patterns and perfusion pressures. In this study, hemostatic clips were used to obstruct the ureter of one kidney at the level of the ischiadic artery (IA) in anesthetized 3-wk-old chicks (Gallus domesticus). Kidney tissue upstream from the ureteral obstruction degenerated, leaving an intact caudal renal division with one route of arterial inflow branching from the IA. Renal function studies were conducted, using general anesthesia, when the birds reached 12-15 wk of age. A snare placed around the IA was used to unilaterally decrease renal arterial perfusion pressure (RAPP) for the experimental kidney. Under control conditions (snare loose), urine flow rates (UFR), glomerular filtration rates (GFR), clearance of p-aminohippuric acid, and fractional excretion of Na, K, Ca, and PO4 did not differ significantly, per gram of kidney weight, when experimental and intact contralateral kidneys were compared. Gradual tightening of the IA snare reduced RAPP stepwise. UFR decreased significantly from the initial control value when RAPP reached 40 mmHg, and urine flow ceased completely when RAPP reached 30-35 mmHg. In four of five birds, GFR did not decrease significantly between 110 and 60 mmHg but did decrease significantly below 60 mmHg. Urine osmolality was inversely correlated with UFR. Clearance of PAH did not decrease significantly from control values as RAPP ranged from 100 to 37 mmHg, possibly caused by increased renal portal blood flow. Overall, these results provide the first direct demonstration that in domestic fowl GFR is autoregulated at reduced RAPP.

Influence of Prostaglandin E and Reduction of Renal Arterial Pressure on Renin Release by the Dog Kidney

The influence of PGE1 infusion into the renal artery of dogs n renal hemodynamics and renin release (RR) was examined, with or without simultaneous reduction in renal arterial perfusion pressure. The degree of reduction in renal arterial pressure was such as to remain in the autoregulatory range. PGE1 is a known stimulator of RR. The objective of the experiment was to attempt to determine whether or not PGE1 and reduction of renal arterial pressure (baroreceptor mechanisms) operated by a similar receptor-effector mechanism, or by different mechanisms. Evidence is supplied that supports the former case (similar receptor-effector mechanism).

Importance of efferent arteriolar vascular tone in regulation of proximal tubule fluid reabsorption and glomerulotubular balance in the rat.

Micropuncture study was performed in 21 mildly volume-expanded Munich-Wistar rats before and during partial aortic constriction to examine the effects of endogenous prostaglandins (PG) and angiotensin II (AII) on single nephron glomerular filtration rate (SNGFR) and absolute proximal reabsorption rate (APR). Animals received either vehicle (group 1), indomethacin (group 2), or indomethacin plus saralasin (group 3). Before aortic constriction, these inhibitors were without effect on values of SNGFR and APR. In group 1 rats, reduction in mean renal arterial perfusion pressure (RAP) to approximately 65 mm Hg resulted in marked and proportional declines in SNGFR and APR. With equivalent reduction in RAP in group 2 rats, however, SNGFR fell to a lesser extent and APR tended to increase slightly above preconstriction values. Indomethacin administration was therefore associated with disruption of glomerulotubular balance. In view of the roughly equivalent declines in afferent arteriolar resistance measured in groups 1 and 2, the magnitude of increase in efferent arteriolar resistance (R(E)) appeared to be of major importance in determining the observed presence or absence of glomerulotubular balance. Thus, the lesser fall in SNGFR in group 2 than in group 1 was a result of the higher value for glomerular capillary hydraulic pressure in group 2, a consequence of the higher value of R(E). The higher average value for APR during reduced RAP in group 2 than in group 1 is also attributable to this pronounced rise in R(E), the effect of which was to augment the net reabsorptive pressure both by favoring higher postglomerular oncotic pressure and lower downstream (peritubular capillary) hydraulic pressure. Since intrarenal release of AII is enhanced when RAP declines, and because AII is known to raise R(E) selectively, it is likely that endogenous AII brought about the marked increase in R(E) in group 2, which was readily demonstrable only in indomethacin-treated rats, presumably because endogenous PG synthesis was suppressed. In keeping with this conclusion, when the action of endogenous AII was inhibited by saralasin in group 3 rats, reduction in RAP failed to induce a rise in R(E), so that net filtration and reabsorption pressures again declined proportionally, as did SNGFR and APR. The present evidence therefore suggests that glomerulotubular balance is influenced to an important extent by the prevailing vasomotor tone of the efferent arteriole.