Biomedical subjects

R J Roman

Publications and source records attributed to R J Roman.

At least 145 records · Page 8Linked to original sources

PubMed1990

Role of blood volume expansion in Dahl rat model of hypertension.

Continuous measurement and servo control (SC) of total body weight of unrestrained rats were used to investigate the role of volume expansion in the development of hypertension in Dahl salt-resistant (SR) and Dahl salt-sensitive (SS) rats. A change in sodium intake from 1 to 20 meq/day was associated with an increase in total body weight of 7.2% in both SS and SR rats over 96 h. Plasma sodium (pNa) increased from 145.0 to 147.4 meq/l in both SS (n = 10) and SR (n = 10) rats. Only in the SS rats was the volume expansion associated with an increase in arterial pressure of 27 +/- 3 mmHg. Prevention of the volume expansion by SC blocked the rise in arterial pressure in the SS rats (n = 10) but increased pNa from 143.5 to 152.4 meq/l. Hematocrit fell from 36.6 to 27.5% in both non-SC groups but decreased less in SC groups (35.7 to 32.0%). Plasma volume expansion from 17.6 +/- 0.6 to 25.2 +/- 0.8 ml in non-SC rats was greatly blunted by SC. In non-SC rats, SS (n = 10) and SR (n = 9) rats an increase in salt intake was associated with a rise in cardiac output from 413 +/- 6 to 507 +/- 12 ml.min-1.kg-1 in both groups. These results indicate that fluid retention is required to trigger the rise of pressure in Dahl SS rats.

Animals↗

PubMed1990

Assessment of muscle blood flow by laser-Doppler flowmetry during hemorrhage in SHR.

Skeletal muscle blood flow was assessed via laser-Doppler flowmetry (LDF) in the gracilis muscle of anesthetized 12- to 15-wk-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) control rats subjected to graded hemorrhage. Tissue perfusion was assessed at 20 specific sites in the muscle before and 20 min after each of five successive 1-ml withdrawals of blood. Mean LDF signals recorded from the gracilis muscle of SHR and WKY were similar during the prehemorrhage control period. After hemorrhage, mean arterial pressure and calculated vascular resistance of the gracilis muscle were higher in SHR than in WKY, and SHR exhibited a greater reduction of LDF signal in response to hemorrhage than WKY. Although SHR and WKY had a similar number of low flow sites (LDF signal less than 0.17 V) during the control period, successive blood volume withdrawals led to a significantly greater increase in the number of poorly perfused areas in the muscles of the hypertensive animals. The results of this study suggest that LDF is a useful tool to assess tissue perfusion during circulatory stress and that hemorrhage causes a greater decrease in skeletal muscle blood flow in SHR than in WKY. More severe reductions in tissue perfusion may contribute to the reduced ability of hypertensive animals to survive after hypotensive hemorrhage.

Animals↗

PubMed1990

Role of renal interstitial hydrostatic pressure in natriuretic response to ANP.

The present study evaluated the role of changes in renal interstitial hydrostatic pressure (RIHP) in the natriuretic response to atriopeptin III (AP III). In control animals, infusion of AP III (100 ng.kg-1.min-1 iv) increased fractional excretion of sodium, potassium, lithium, and water while glomerular filtration rate and renal blood flow were unaltered. The natriuretic response to AP III was associated with a significant elevation in RIHP from 5.6 +/- 0.8 to 8.1 +/- 1.0 mmHg. In rats pretreated with amiloride (1 mg/kg) to block sodium transport in the collecting duct, basal sodium excretion was elevated, but infusion of AP III still increased RIHP and the fractional excretion of sodium, water, and lithium by the same amount as was observed in the control animals. Removal of the renal capsule completely blocked the rise in interstitial pressure in the renal cortex in amiloride-treated rats, but it did not eliminate the elevation in sodium, water, and lithium excretion produced by AP III. To determine whether changes in renal medullary interstitial pressure could play a role in the residual natriuretic response to AP III in these animals, cortical and medullary interstitial pressure were simultaneously measured in rats with a decapsulated kidney. In this group, AP III increased renal medullary interstitial pressure, while cortical interstitial pressure was unaltered. These results are consistent with the view that changes in renal medullary hemodynamics and RIHP contribute to the natriuretic effect of atrial natriuretic peptide by elevating distal delivery of sodium from deep nephrons.

Amiloride↗

PubMed1990

Influence of prostaglandins on papillary blood flow and pressure-natriuretic response.

The present study examined whether renal prostaglandins influence the pressure-natriuretic response by altering medullary hemodynamics or renal interstitial pressure. The diuretic and natriuretic responses to changes in renal perfusion pressure were compared in control rats (n = 15) and in rats receiving either meclofenamate (2 mg/kg, n = 9) or indomethacin (2 mg/kg, n = 4). In control rats, urine flow and sodium excretion increased from 10 +/- 2 to 118 +/- 10 microliters/min/g kidney wt and from 1.8 +/- 0.3 to 21.0 +/- 1.5 mueq/min/g kidney wt, respectively, when renal perfusion pressure was increased from 109 to 167 mm Hg. Urinary excretion of prostaglandin E2 and thromboxane B2 increased significantly by 152% and 190%, respectively. Meclofenamate lowered thromboxane B2 and prostaglandin E2 excretion and prevented the increase in eicosanoid excretion produced by elevations in perfusion pressure. The pressure-diuretic and pressure-natriuretic responses of rats given meclofenamate or indomethacin were approximately half of those observed in the control rats. Papillary blood flow increased 21% and renal interstitial pressure rose from 5.0 +/- 0.7 to 8.2 +/- 0.7 mm Hg in control rats when pressure was elevated from 100 to 150 mm Hg. Meclofenamate and indomethacin lowered papillary blood flow and renal interstitial pressure and blunted the increases in these values produced by elevations in perfusion pressure. These results support the view that renal prostaglandins modulate the pressure-natriuresis relation by altering renal medullary hemodynamics and suggest that an intact renal prostaglandin system is necessary for the full expression of the medullary hemodynamic and natriuretic responses to increases in renal perfusion pressure.

Animals↗

PubMed1990

Enhanced vascular tone in the renal vasculature of spontaneously hypertensive rats.

The renal microvascular responses of Wistar-Kyoto and spontaneously hypertensive rats to changes in perfusion pressure were compared using a juxtamedullary nephron microvascular preparation perfused in vitro with a physiological salt solution containing 5% albumin. In the spontaneously hypertensive rats, the internal diameters of arcuate and interlobular arteries and the proximal and distal afferent arterioles averaged 307 +/- 26, 52 +/- 2, 24 +/- 0.9, and 22 +/- 1.2 microns, respectively, at 80 mm Hg. They were 18-35% smaller (p less than 0.05) than the corresponding vessels measured in Wistar-Kyoto rats. In low calcium media, the arcuate and interlobular arteries and the proximal and distal afferent arterioles of spontaneously hypertensive rats exhibited a greater dilation than the vessels of Wistar-Kyoto rats. These observations suggest that the diameters of the preglomerular vasculature of the spontaneously hypertensive rats are reduced because of an elevated vascular tone rather than structural changes narrowing the lumen of these vessels. These results suggest that enhanced vascular tone in the preglomerular vasculature of juxtamedullary nephrons may contribute to the elevated renal medullary vascular resistance and resetting of the pressure-natriuretic relation previously observed in spontaneously hypertensive rats.

Animals↗

PubMed1990

Anti-inflammatory and safety profile of DuP 697, a novel orally effective prostaglandin synthesis inhibitor.

DuP 697 (5-bromo-2[4-fluorophenyl]-3-[4-methylsulfonylphenyl]-thiophene) is a potent inhibitor of paw swelling in nonestablished and established adjuvant arthritis in rats (ED50 = 0.03 and 0.18 mg/kg/day, respectively). DuP 697 had no effect on phenylquinone writhing in rats (ED50 greater than 100 mg/kg), but was analgetic against inflammation-related pain in the Randall-Selitto assay (ED30 = 3.5 mg/kg) and was a very potent antipyretic agent (ED50 = 0.05 mg/kg). The drug was not ulcerogenic in rats at single doses up to 400 mg/kg. DuP 697 (5 mg/kg i.v.) did not alter renal blood flow or the renal vascular response to angiotensin II in furosemide-pretreated, volume-depleted rats. In contrast, indomethacin (5 mg/kg i.v.) decreased renal blood flow and potentiated the renal vascular response to angiotensin II in these animals. DuP 697 was a moderate inhibitor of bull seminal vesicle prostaglandin (PG) synthesis (IC50 = 2.4 X 10(-5) M) and a potent inhibitor of rat brain PG synthesis (IC50 = 4.5 X 10(-6) M) but was ineffective against rat kidney PG synthesis (IC50 7.5 X 10(-5) M). These differential effects of DuP 697 on PG synthesis by various tissues may account for its high potency as an anti-inflammatory and antipyretic agent and its minimal toxicity profile.

Administration, Oral↗

PubMed1989

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.

Animals↗

PubMed1989

Hemodynamics and blood volume in angiotensin II salt-dependent hypertension in dogs.

The sequential effects of an increased daily NaCl intake on hemodynamics, fluid electrolyte balances, and hormonal responses were evaluated in dogs (n = 7) with fixed circulating levels of angiotensin II (ANG II). During the control period, ANG II was infused at 3 ng.kg-1.min-1 while dogs were maintained on an 8 meq NaCl/day diet. Water intake was fixed at 700 ml/day. Continuously recorded (24 h/day) changes of total body weight (TBW) were used as an index of total body water. Cardiac stroke volume and arterial pressure were recorded, and each beat was digitized to provide hourly and 24-h average cardiac output (CO), mean arterial pressure (MAP), and total peripheral resistance (TPR). After three stable control days, daily salt intake was increased to 120 meq for 7 days. TBW increased gradually to 448 +/- 111 g (2.9%, P less than 0.05) above control by day 3. An 11% expansion of blood volume (P less than 0.05) was found (51CR-labeled red blood cells) on day 2 of high NaCl. CO rose 12% and MAP 20% (P less than 0.05) in parallel with TBW by day 4. By day 7, CO remained only 5% elevated, whereas MAP had stabilized at 20% above control levels. TPR remained significantly elevated from days 3 through 7. A positive Na balance averaging 91 +/- 8 meq (P less than 0.05) occurred on day 1. Plasma Na concentration was increased 2-3 meq/l above control throughout the period of high-salt intake. Plasma renin activity and aldosterone levels decreased to nearly undetectable levels, vasopressin rose slightly, and atrial natriuretic peptide levels increased significantly. Dogs maintained at 8 meq/day NaCl during the same infusion of ANG II showed no changes in MAP, CO, TPR, or TBW. In summary, the salt-induced hypertension was consistently related to small but significant fluid retention, blood volume expansion, elevations of cardiac output, and a gradual increase in TPR.

Angiotensin II↗

PubMed1989

Role of renal interstitial hydrostatic pressure in the pressure diuresis response.

The present study examines the role of renal interstitial hydrostatic pressure (RIHP) in the pressure-diuretic and -natriuretic response. The relationships between RIHP, sodium excretion, and renal perfusion pressure (RPP) were determined in antidiuretic and volume-expanded (VE) rats with an intact or decapsulated kidney. RIHP was measured by use of the implanted capsule technique. RIHP increased significantly from 7.5 +/- 0.8 to 12.0 +/- 1.4 mmHg in VE animals and from 3.3 +/- 0.4 to 5.2 +/- 0.7 mmHg in antidiuretic rats after RPP was varied from 100 to 150 mmHg. The pressure-natriuretic response of the antidiuretic rats was blunted compared with that observed in the VE rats. Decapsulation of the kidney in VE rats lowered RIHP and reduced, but did not eliminate, the pressure-natriuretic response. To determine whether this residual response was related to changes in interstitial pressure in the medulla, cortical (CIHP) and medullary interstitial hydrostatic pressures (MIHP) were simultaneously measured in VE rats with an intact or decapsulated kidney. In control rats CIHP and MIHP were similar at all levels of RPP studied. In rats with the renal capsule removed MIHP was higher than CIHP and rose significantly from 6.7 +/- 0.8 to 9.2 +/- 0.8 mmHg when RPP was varied from 100 to 150 mmHg. These results indicate that pressure diuresis and natriuresis is accompanied by changes in RIHP and the response is modulated by the basal level of RIHP. These findings suggest that changes in MIHP may serve as an intrarenal signal for this response.

Animals↗

PubMed1989

Natriuretic effect of atriopeptin III in rats with papillary necrosis.

This study compared the effects of atriopeptin III (AP III) on sodium excretion and renal interstitial hydrostatic pressure (RIHP) in control rats and in rats pretreated with 2-bromoethylamine (BEA) to produce papillary necrosis. In control rats, infusion of AP III (100 ng.kg-1.min-1) increased sodium excretion from 2.2 +/- 0.7 to 6.4 +/- 0.9 microeq.min-1.g kidney wt-1 and RIHP from 6.8 +/- 0.7 to 8.7 +/- 0.9 mmHg, whereas glomerular filtration rate and renal blood flow were unaltered. Similar results were obtained in rats pretreated with BEA 48 h before the experiment. In rats studied 6 wk after BEA treatment, the papilla was absent and there was atrophy of juxtamedullary nephrons. AP III did not alter sodium excretion or RIHP in this group of rats. These results indicate that 1) an intact renal papilla and/or juxtamedullary nephron population may be required for the natriuretic effect of AP III; 2) the papillary injury 48 h after BEA is not sufficient to abolish the natriuretic response to AP III; and 3) elevations in RIHP may play a role in the natriuretic response to AP III.

Acetazolamide↗

PubMed1989

Pressure-dependent contraction of rat juxtamedullary afferent arterioles.

Pressure-diameter relations were studied in rat afferent arterioles using an isolated, juxtamedullary nephron preparation perfused with a saline solution containing 5% albumin. Angiotensin I (10 microM), angiotensin II (0.1 microM), and norepinephrine (10 microM) increased perfusion pressure, and norepinephrine, but not angiotensin I or II, contracted afferent arterioles, indicating that the vessels are reactive. The control diameter of the afferent arterioles that exhibited pressure-dependent contraction (n = 58) averaged 30.8 +/- 1.1 micron at perfusion pressure of 80 mm Hg. When pressure was increased from 80 to 120 and then to 180 mm Hg, the diameter of these arterioles decreased by 16.4 +/- 2.1%. Glomerular capillary pressure was well autoregulated and averaged 45.2 +/- 2.2, 50.2 +/- 2.4, and 53.0 +/- 3.0 mm Hg, respectively, at perfusion pressures of 80, 120, and 180 mm Hg. Administration of vasodilators or a Ca2+-free solution eliminated the contractile response to pressure elevations; rather, the diameter of these vessels increased significantly by 17.5 +/- 5.1% and 32.0 +/- 9.4%, respectively, when pressure was increased from 80 to 180 mm Hg. Blocking tubuloglomerular feedback mechanism, with furosemide or by removal of the renal papilla (which interrupts the delivery of fluid to the macula densa), eliminated the pressure-dependent contraction of the afferent arterioles. Instead the diameter of these vessels increased by 27.0 +/- 7.8% and 36.0 +/- 5.6%, respectively, when the pressure was increased from 80 to 120 and then to 180 mm Hg. These results demonstrate that juxtamedullary nephrons perfused in vitro autoregulate glomerular capillary pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗

PubMed1989

Effects of complement depletion on glomerular eicosanoid production and renal hemodynamics in rat nephrotoxic serum nephritis.

The role of complement in mediating the changes in renal hemodynamics and glomerular eicosanoid synthesis after the administration of heterologous antibody against rat glomerular basement membrane (AGBM) was studied in Munich-Wistar rats. AGBM serum decreased glomerular filtration rate (GFR) and increased glomerular thomboxane B2 (TxB2) production without associated changes in glomerular prostaglandin E2 (PGE2) or PGF2 alpha production. Pretreatment of rats with cobra venom factor to deplete complement blocked the fall in GFR produced by AGBM without altering the increment in glomerular TxB2 production. In these animals, glomerular PGE2 synthesis was elevated. The results indicate that the salutary effects of complement depletion in nephrotoxic serum nephritis are not mediated by changes in the glomerular production of the vasoconstrictor TxA2. An enhanced production of PGE2 may participate in preventing the fall in GFR after AGBM administration in the complement-depleted rats.

Animals↗

PubMed1989

Mechanisms of pressure-induced myogenic activation of cerebral and renal arteries: role of the endothelium.

Control of blood flow is mediated by a variety of metabolic, neurogenic, myogenic and other mechanisms. The basic response of the myogenic mechanisms is a mechanical stimulus that activates vascular muscle via a sensor within the vessel wall. We studied the way in which increases in transmural pressure within the physiological range can activate cerebral and renal vascular muscle by depolarizing the muscle cell membrane. These membrane electrical effects depend on the external calcium concentration [( Ca2+]o) and on the presence of an intact vascular endothelium. Bioassay experiments have shown that an elevation in pressure releases a vasoactive product(s) from endothelial cells, which mediates the pressure-dependent membrane depolarization in these vessels. These responses may affect the autoregulation of blood flow in that vessels become smaller as pressures increase between 60 and 160 mmHg.

Animals↗

PubMed1988

Influence of kinins and angiotensin II on the regulation of papillary blood flow.

The influence of kinins and angiotensin II on the regulation of renal cortical and papillary blood flow and sodium and water excretion was examined in rats. Superficial cortical and papillary blood flows were measured using a laser-Doppler flowmeter. Papillary blood flow increased 50% after enalaprilat (60 micrograms/kg) and phosphoramidon (5.5 micrograms.kg-1.min-1) were given along with 0.3 M sodium bicarbonate solution to inhibit degradation of kinins and enhance urinary kallikrein activity. Infusion of a kinin antagonist, D-Arg-Hyp-Thi-D-Phe-bradykinin (5 micrograms/min), returned papillary blood flow to control levels. Urine flow and sodium excretion increased after the administration of the kininase inhibitors and sodium bicarbonate, while glomerular filtration rate (GFR) and outer cortical blood flow were unaltered. The kinin antagonist did not alter sodium and water excretion in rats receiving the kininase inhibitors and bicarbonate. Administration of the kinin antagonist alone lowered papillary blood flow by 20%, without affecting outer cortical blood flow or GFR. Urine flow decreased and urine osmolality increased after the rats received the kinin antagonist, but sodium excretion remained unaltered. To assess the role of angiotensin II in the control of papillary blood flow, kinin receptors were blocked by infusion of an antagonist, and the effects of enalaprilat and saralasin were studied. Papillary blood flow increased after blockade of the angiotensin II system in rats receiving the kinin antagonist. These results indicate that the kallikrein-kinin and renin-angiotensin systems participate in the regulation of papillary blood flow.

Angiotensin II↗

PubMed1988

Renal nerves and the development of Dahl salt-sensitive hypertension.

Several experimental forms of hypertension require intact renal innervation for the development or maintenance (or both) of the elevated arterial pressure. We determined the relationships between urinary sodium and water excretion and arterial pressure in Dahl salt-sensitive rats (DS) with innervated (n = 6) and denervated (n = 7) kidneys after switching from a low to a high sodium diet. Arterial pressure significantly increased in both groups within 48 hours after they began to eat an 8% sodium chloride diet. This hypertension increased to 188 +/- 9 and 190 +/- 7 mm Hg, respectively, in rats with innervated and denervated kidneys after 12 days. Mean arterial pressures were not significantly different between groups on any day. The rise in arterial pressure of DS placed on a high sodium intake was associated with an elevation of urine flow rate and urinary sodium excretions in rats with either innervated or denervated kidneys. Urine flow rates and urinary sodium excretions were greater in denervated than in innervated rats on Days 4 through 7 after beginning the high sodium diet. This diuresis and natriuresis in rats with denervated kidneys were associated with greater water and sodium intakes on Days 4 to 7 of the high sodium diet when compared with rats with innervated kidneys. These results demonstrate that, following exposure to a high sodium intake, DS have increased arterial pressure within 24 hours. The development of this arterial hypertension is not dependent on intact renal innervation. In conscious DS, the renal innervation does participate in the regulation of urinary sodium excretion by promoting renal sodium and water reabsorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Renal cortical and papillary blood flow in spontaneously hypertensive rats.

The present study examined whether an alteration in renal medullary hemodynamics is associated with the development of hypertension in the spontaneously hypertensive rat (SHR). The relationships between whole kidney, cortical and papillary blood flows, and renal perfusion pressure were compared in 3- to 5-, 6- to 9-, and 12- to 16-week-old SHR and Wistar-Kyoto rats (WKY). Cortical and papillary blood flows were similar in the different age groups of SHR and WKY over most of the range of perfusion pressure studied. Control papillary blood flows, determined at a renal perfusion pressure equal to the mean arterial pressure of each animal, were not significantly different in the 3- to 5- and 12- to 16-week-old SHR in comparison to values observed in age-matched WKY. In contrast, the control papillary blood flow was 30% lower in 6- to 9-week-old SHR in comparison to the value observed in WKY. Papillary blood flows were significantly less in all age groups of SHR than the corresponding flows measured in WKY when they were compared at equivalent renal perfusion pressures. These findings indicate that medullary vascular resistance is elevated even in very young SHR and suggest that alterations in vasa recta hemodynamics may participate in the development of hypertension by shifting the pressure-natriuresis relationship toward higher pressures.

Age Factors↗

PubMed1988

Pressure-diuresis in volume-expanded rats. Cortical and medullary hemodynamics.

This study evaluated whether pressure-diuretic and pressure-natriuretic responses are associated with alterations in vasa recta hemodynamics. Autoregulation of cortical and papillary blood flow was studied using a laser-Doppler flowmeter in volume-expanded and hydropenic rats. Superficial cortical flow and whole kidney renal blood flow were autoregulated in volume-expanded rats and decreased by less than 10% after renal perfusion pressure was lowered from 150 to 100 mm Hg. In contrast, papillary blood flow was not autoregulated and fell by 24 +/- 2%. The failure of papillary blood flow to autoregulate was due to changes in the number of perfused vessels as well as to alterations in blood flow in individual ascending and descending vasa recta. Pressure in vasa recta capillaries increased from 6.8 +/- 0.8 to 13.8 +/- 1.2 mm Hg after renal perfusion pressure was elevated from 100 to 150 mm Hg, and renal interstitial pressure rose from 7.4 +/- 0.8 to 12.3 +/- 1.4 mm Hg. In hydropenic rats, papillary blood flow was autoregulated to a significant extent, but it still decreased by 19% after renal perfusion pressure was lowered from 150 to 100 mm Hg. The pressure-diuretic and pressure-natriuretic responses in hydropenic rats were blunted in comparison to those observed in volume-expanded rats. These findings indicate that the pressure-diuretic and pressure-natriuretic responses are associated with changes in vasa recta hemodynamics and renal interstitial pressure.

Animals↗

PubMed1988

Pressure-diuresis in volume-expanded rats. Tubular reabsorption in superficial and deep nephrons.

Micropuncture experiments were performed in volume-expanded rats to better define the nephron segments in which changes in renal perfusion pressure inhibit tubular reabsorption. Neural influences on the kidney were eliminated by renal denervation, and plasma levels of vasopressin, aldosterone, corticosterone, and norepinephrine were maintained at fixed levels by i.v. infusion. Fractional excretion of sodium, chloride, and water increased markedly after renal perfusion pressure was elevated from 110 to 150 mm Hg. Renal blood flow, glomerular filtration rate, and single nephron glomerular filtration rate measured from deep and superficial nephrons were unsaltered. Reabsorption of chloride and water in the proximal tubule of superficial nephrons decreased by 10% after renal perfusion pressure was elevated and contributed to the pressure-diuretic response. Changes in renal perfusion pressure also altered the reabsorption of water and chloride in juxtamedullary nephrons. The percentage of the filtered water load reaching the tip of the loop of Henle increased from 19.8 +/- 2.9 to 38.1 +/- 3.0% after renal perfusion pressure was elevated. Chloride delivery rose from 34.2 +/- 4.3 to 65.2 +/- 4.8% of the filtered load. These results support the view that alterations in medullary hemodynamics participate in the pressure-natriuretic response by inhibiting tubular reabsorption in the proximal tubule or the thin descending limb of the loop of Henle (or both) of juxtamedullary nephrons.

Animals↗