Levels Of Renal Perfusion Pressure Research Articles

Effects of Renal Perfusion Pressure on Renal Medullary Hydrogen Peroxide and Nitric Oxide Production

Studies were designed to determine the effects of increases of renal perfusion pressure on the production of hydrogen peroxide (H(2)O(2)) and NO(2)(-)+NO(3)(-) within the renal outer medulla. Sprague-Dawley rats were studied with either the renal capsule intact or removed to ascertain the contribution of changes of medullary blood flow and renal interstitial hydrostatic pressure on H(2)O(2) and NO(2)(-)+NO(3)(-) production. Responses to three 30-minute step changes of renal perfusion pressure (from approximately 85 to approximately 115 to approximately 145 mm Hg) were studied using adjustable aortic occluders proximal and distal to the left renal artery. Medullary interstitial H(2)O(2) determined by microdialysis increased at each level of renal perfusion pressure from 640 to 874 to 1593 nmol/L, as did H(2)O(2) urinary excretion rates, and these responses were significantly attenuated by decapsulation. Medullary interstitial NO(2)(-)+NO(3)(-) increased from 9.2 to 13.8 to 16.1 mumol/L, with parallel changes in urine NO(2)(-)+NO(3)(-), but decapsulation did not significantly blunt these responses. Over the range of renal perfusion pressure, medullary blood flow (laser-Doppler flowmetry) rose approximately 30% and renal interstitial hydrostatic pressure rose from 7.8 to 19.7 cm H(2)O. Renal interstitial hydrostatic pressure and the natriuretic and diuretic responses were significantly attenuated with decapsulation, but medullary blood flow was not affected. The data indicate that pressure-induced increases of H(2)O(2) emanated largely from increased tubular flow rates to the medullary thick-ascending limbs of Henle and NO largely from increased medullary blood flow to the vasa recta. The parallel pressure-induced increases of H(2)O(2) and NO indicate a participation in shaping the "normal" pressure-natriuresis relationship and explain why an imbalance in either would affect the blood pressure salt sensitivity.

Exogenous L‐Arginine (L‐Arg) blunts Angiotensin II (AngII)‐mediated renal vasoconstriction and improves pressure‐diuresis

Administration of exogenous L‐Arg reverses AngII‐mediated hypertension and kidney disease in conscious rats. The present study assessed renal hemodynamics and pressure‐diuresis in Inactin‐anesthetized Sprague Dawley rats (n=4‐5/group) infused with saline vehicle, AngII (20 ng/kg/min, iv) or AngII + L‐Arg (300 ?g/kg/min, iv). Increasing renal perfusion pressure (RPP) from 100±1 to 142±3 mmHg with aortic clamps resulted in an increase in urine flow in control rats from 5.3±0.6 to 56.1±12.5 ?l/min/gram kidney weight (gkwt). In comparison, the pressure‐dependent increase in urine flow was significantly depressed by 50‐65% at all levels of RPP in AngII‐infused rats. Supplementation of L‐Arg restored pressure‐dependent diuresis to levels not significantly different from control rats. In control rats, glomerular filtration rate (GFR) averaged 1.4±0.4 ml/min/gkwt and renal blood flow (RBF) averaged 6.8±0.7 ml/min/gkwt at the lowest RPP. RBF was significantly reduced by 45% in AngII‐infused rats. Co‐infusion of L‐Arg reversed the AngII‐mediated changes in RBF to values not different from control. These data indicate that AngII‐mediated vasoconstriction and blunting of pressure‐diuresis is reversed by exogenous L‐Arg, demonstrating an important role for nitric oxide to blunt the renal vasoconstrictor, anti‐diuretic, and pro‐hypertensive effects of AngII. Supported by DK‐62803.

Effect of renal perfusion pressure on responses of intrarenal blood flow to renal nerve stimulation in rabbits.

1. We investigated how sympathetic nerve activity and renal perfusion pressure (RPP) interact in controlling renal haemodynamics in pentobarbitone-anaesthetized rabbits. 2. Renal blood flow (RBF) was reduced by electrical renal nerve stimulation (0.5-8 Hz), with RPP set using an extracorporeal circuit to 65, 100 and 135 mmHg. 3. Responses of RBF and cortical laser Doppler flux to renal nerve stimulation were blunted by increased RPP. For example, 4 Hz stimulation reduced RBF by 68 +/- 7% with baseline perfusion pressure approximately 65 mmHg, but only by 22 +/- 3% at approximately 135 mmHg. Medullary laser Doppler flux was less responsive than cortical laser Doppler flux to renal nerve stimulation and its response was not dependent on perfusion pressure. 4. When perfusion pressure was clamped at its baseline level during renal nerve stimulation, responses of RBF and cortical laser Doppler flux, but not medullary laser Doppler flux, were still blunted with increased baseline perfusion pressure. 5. A frequency rich stimulus was applied to assess the effects of perfusion pressure on dynamic neural control of RBF. Renal blood flow responded similarly at each level of perfusion pressure, as a low-pass filter with a pure time delay. 6. Our results suggest that, in the rabbit extracorporeal circuit model, increased RPP blunts the ability of steady state renal nerve stimulation to reduce cortical, but not medullary perfusion. However, in this model the level of RPP appears to have little impact on dynamic neural control of RBF.

Chromosome 1 blood pressure QTL region influences renal function curve and salt sensitivity in SHR.

One or more quantitative trait locus (QTL) for blood pressure (BP) exists on rat chromosome 1, in the vicinity of the Sa gene. The present work examined whether this QTL region: 1) alters pressure-natriuresis relationship and 2) affects the BP response to salt load. Male spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) rats, and rats from an SHR congenic strain that contains a WKY chromosome 1 segment spanning the BP QTL region (SHR. WKY-Sa) were used. In an acute study in anesthetized animals, renal function was measured at several levels of renal perfusion pressure. In a chronic study, BP was measured in freely moving rats using telemetry during normal and high sodium intake (2% NaCl as drinking water for 2 wk). WKY rats showed a significantly higher glomerular filtration rate and increased pressure-natriuresis compared with SHR. SHR.WKY-Sa also demonstrated an increased glomerular filtration rate and enhanced pressure-natriuresis, associated with a lower tubular sodium reabsorption, compared with SHR. These modifications were accompanied by a lower basal BP in SHR.WKY-Sa compared with SHR and a markedly reduced BP response to salt load. These findings suggest that the BP QTL(s) present in this region of chromosome 1 influences BP and salt sensitivity, at least partly, by modulating pressure-natriuresis.

Blood pressure variability and urine flow in the conscious dog.

Pressure-dependent urine production is considered to be a major factor in long-term blood pressure control. The phenomenon has been well characterized for fixed levels of renal perfusion pressure (RPP), but the influence of physiological fluctuations in RPP and spontaneous variations in renal blood flow (RBF) on short-term urine flow (UV) remain unclear. To clarify this issue, we studied the interdependence of RPP, RBF, and UV in 13 conscious foxhounds during a single-step pressure reduction, under normal conditions, and with induced pressure changes. Reducing RPP in a single step to approximately 80 mmHg revealed short response times of RBF (0.4 +/- 0.1 s, n = 7) as well as of UV (8.1 +/- 0.8 s, n = 7). Under control conditions, UV was coupled with spontaneous variations of RBF (r = 0.94, P < 0.001), in contrast to RPP, which showed no significant correlation with UV (r = 0.09, P = NS). To discern the pressure and blood flow dependency of UV at a reduced RPP, we induced 0.9-mHz blood pressure oscillations (80 +/- 10 mmHg), which phase shifted RPP and RBF. Conversely, under these conditions, UV was dependent on RPP (r = 0.95, P < 0.001). These results suggest that spontaneous fluctuations in RBF around a normal baseline level lead to concomitant changes in urine production, in contrast to physiological short-term oscillations in RPP, which are not correlated to changes in UV. However, during induced oscillations of perfusion pressure, the blood flow dependence was no longer observed and UV was entirely pressure dependent.

Induction of P4504A activity improves pressure-natriuresis in Dahl S rats.

Clofibrate has been reported to prevent the development of hypertension in Dahl S rats, but its mechanism of action remains to be determined. The present study examined the effects of clofibrate on renal P4504A activity and the pressure natriuresis relationship in Dahl S rats. Dahl S and R rats fed a low-salt diet (0.4% NaCl) were given either clofibrate (240 mg/kg/d) or vehicle (20 mmol/L Na2CO3) in their drinking water for 1 week and then switched to a high salt diet (8% NaCl) while continuing drug treatment. After 3 weeks, mean arterial pressure in ketamine-Inactin anesthetized rats averaged 121+/-2 (n=8) in Dahl R, 173+/-8 (n=6) in Dahl S, and 139+/-4 mm Hg (n=7) in clofibrate-treated Dahl S rats. Increasing renal perfusion pressure (RPP) from 100 to 150 mm Hg in Dahl R rats increased sodium excretion (U(Na)V) from 2.9+/-0.7 to 9.7+/-3.2 micromol/min/g kwt. In contrast, the pressure natriuresis relation was blunted in Dahl S rats and U(Na)V only increased from 2.7+/-0.9 to 6.1+/-1.3 micromol/min/g kwt. The pressure natriuresis relation was improved in clofibrate-treated Dahl S rats and U(Na)V increased from 5.1+/-1.3 to 16.7+/-2.6 micromol/min/g kwt. At similar levels of RPP, the fractional excretion of sodium tended to be higher in clofibrate-treated than in vehicle-treated Dahl S rats, but not significantly. Glomerular filtration rate (GFR) was 40% higher in clofibrate- compared to vehicle-treated Dahl S rats (0.9+/-0.2 versus 0.6+/-0.2 mL/min/g kwt), and was not significantly different from the values seen in Dahl R rats (0.9+/-0.1 mL/min/g kwt). Clofibrate induced the expression of P4504A protein in the renal cortex and outer medulla of Dahl S rats. These data suggest that induction of renal P4504A activity with clofibrate improves the pressure natriuresis relation in Dahl S rats by primarily increasing GFR.

Pressure natriuresis after adrenomedullin in anesthetized spontaneously hypertensive rats.

Adrenomedullin (ADM), a peptide with potent vasodilatory and natriuretic actions, is elevated in patients with essential hypertension. Because pharmacological doses of ADM result in renal vasodilation and natriuresis, it has been suggested that ADM may play a modulatory role in hypertension through potential actions on renal pressure natriuresis. However, it is unclear whether elevation of plasma ADM within the pathophysiological range has similar actions. To determine the effects of pathophysiological doses of ADM on blood pressure and on the relationship between renal perfusion pressure (RPP) and renal hemodynamics and sodium excretion, renal function was determined at RPPs of 80, 105, 130, and 155 mm Hg in spontaneously hypertensive rats (SHR) infused with ADM at 50 ng x kg(-1) x min(-1) (ADM-50, n=5) and at 100 ng x kg(-1) x min(-1) (ADM-100, n=5) and in control SHR (n=5). Decreasing RPP from 155 to 80 mm Hg in control SHR decreased (P<.05) absolute sodium excretion from 0.81+/-0.25 to 0.04+/-0.02 microEq/min, fractional sodium excretion from 0.32+/-0.11% to 0.06+/-0.04%, and urine flow rate from 11.5+/-2.8 to 1.03+/-0.31 microL/min. ADM infusion elevated (P<.05) plasma ADM levels in ADM-infused SHR (679+/-47 pg/mL in ADM-50, 858+/-79 in ADM-100) compared with control (79.5+/-27.8). However, although reduction of RPP from 155 to 80 mm Hg in ADM rats decreased absolute sodium excretion (ADM-50, 0.98+/-0.10 to 0.09+/-0.04 microEq/min; ADM-100, 0.95+/-0.09 to 0.07+/-0.02 microEq/min), fractional sodium excretion (ADM-50, 0.31+/-0.03% to 0.17+/-0.04%; ADM-100, 0.33+/-0.02% to 0.09+/-0.01%), and urine flow (ADM-50, 13.6+/-1.4 to 1.73+/-0.75 microL/min; ADM-100, 13.5+/-1.5 to 1.07+/-0.16 microL/min), these decreases were not different from values found in controls. Renal plasma flow and glomerular filtration rate were also similar in control and ADM-treated SHR at each level of RPP. Thus, acute increases in ADM to levels found in pathophysiological conditions have no effect on blood pressure, pressure natriuresis, or renal autoregulation in the SHR. These findings do not support the hypothesis that ADM serves as a modulating factor in hypertension, at least in the SHR.

Reduction in renin release and renal vascular resistance by H(+)-K(+)-ATPase inhibition.

Results from previous experiments in our laboratory suggested that a H(+)-K(+)-adenosinetriphosphatase (H(+)-K(+)-ATPase) was present in vascular smooth muscle. Here we analyzed the effects on regulation of renal vascular function in anesthetized dogs of inhibition of the H(+)-K(+)-ATPase by a highly specific inhibitor, NC-1300-B. The compound was injected intravenously, 15 mg/kg (5.8 x 10(-5) mol wt/kg), into one group of six dogs, whereas saline was given to a control group of eight. Renal function was measured at controlled levels of renal perfusion pressure ranging from 110 to 60 mmHg. Renal blood flow (RBF) was higher in the treated group at all levels of perfusion pressure; at 70 mmHg, the treated group RBF was 5.85 +/- 1.00 ml.min-1.g kidney wt-1, 71% greater than that of the control group. Glomerular filtration rate (GFR) mean values of the two groups were not significantly different at any perfusion pressure level. Renin release was inhibited (P < 0.01) by H(+)-K(+)-ATPase inhibition; at 90 mmHg, the control group mean was 14.3 +/- 4.3 units, 4.47 times greater than the treated group mean of 3.2 +/- 1.6 units. H(+)-K(+)-ATPase inhibition with NC-1300-B causes profound renal vasodilation and inhibition of renin release without affecting regulation of GFR.

Age-related changes in the pressure diuresis and natriuresis response.

The renal-excretory responses to changes in renal perfusion pressure (RPP) were studied in anesthetized young (3 mo old), adult (12 mo old), and senescent (24 mo old) rats to evaluate whether the pressure diuresis and natriuresis mechanism is altered as a function of age. Experiments were performed in anesthetized animals in which nervous and systemic hormonal influences to the kidney were fixed. Mean arterial pressure was similar in all three groups: 97.6 +/- 2.6, 102.1 +/- 3.7, and 95.2 +/- 5.2 mmHg in young, adult, and senescent rats, respectively. The relationships between RPP and diuresis/natriuresis or fractional excretions of water and sodium were similar in young and adult rats. However, in senescent rats the pressure-diuretic and pressure-natriuretic responses were slightly shifted to the right, so that diuresis and natriuresis were significantly lower at higher levels of RPP. Glomerular filtration rate was well autoregulated, and there were no differences between young and adult rats at each level of RPP. However, a significantly lower glomerular filtration rate was observed in senescent rats. These results indicate an age-related decline in the pressure-dependent sodium and water excretion that appears to be due to a decrease in glomerular filtration and an increase in tubular sodium reabsorption.

Pressure-dependent renin release during chronic blockade of nitric oxide synthase.

We evaluated pressure-dependent stimulation of renin release in rats with sustained hypertension induced by chronic blockade of nitric oxide synthase with N omega-nitro-L-arginine methyl ester (L-NAME) for 5 to 7 days. Rats were anesthetized and catheters were inserted into the carotid artery and abdominal aorta for measurement of arterial pressures. An adjustable snare was placed around the suprarenal aorta, and this snare was tightened to reduce renal perfusion pressure. Pressure-dependent renin release was evaluated in hypertensive rats by reducing renal perfusion pressure to 125, 85, and 65 mm Hg. Renin release was also evaluated in normotensive control rats at these same pressures. Basal systemic arterial pressures averaged 159 +/- 3 and 124 +/- 4 mm Hg (P < .001), respectively, in the L-NAME-treated (n = 22) and normotensive control (n = 18) rats. Basal plasma renin activity was lower in L-NAME than control rats (5.0 +/- 0.3 versus 9.5 +/- 1.3 U, P < .01), and plasma renin activity was markedly attenuated at all comparable levels of renal perfusion pressure. Maximal plasma renin activity levels were achieved at perfusion pressures reduced to 65 mm Hg, and plasma renin activity averaged 14 +/- 2 and 34 +/- 7 U (P < .01) in L-NAME hypertensive and control rats, respectively. However, infusion of the nitric oxide donor sodium nitroprusside similarly stimulated plasma renin activity levels to 39 +/- 3 and 45 +/- 3 U (P > .05), in the hypertensive and normal control groups, respectively. Overall, these findings are consistent with the hypothesis that prolonged L-NAME administration attenuates pressure-dependent renin release by inhibiting nitric oxide formation, which may function as a paracrine mechanism inversely linking renal perfusion pressure with the stimulation of renin release.

Pressure-Diuresis-Natriuresis Response in Hyperthyroid and Hypothyroid Rats

1. Renal responses to changes in renal perfusion pressure were studied in anaesthetized hyperthyroid (thyroxine, 300 micrograms day-1 kg-1) and hypothyroid (methimazole, 0.03% via drinking water) rats to determine whether an abnormality in the pressure-diuresis-natriuresis phenomenon is involved in the resetting of kidney function in these disorders. 2. There were no significant differences between control and hypothyroid rats with respect to the relationships between renal perfusion pressure and absolute or fractional water and sodium excretion. However, in hyperthyroid rats the pressure-diuresis-natriuresis mechanism was impaired. 3. Renal blood flow and glomerular filtration rate were well autoregulated and there were no differences between control and hypothyroid rats at every level of renal perfusion pressure. A significantly lower glomerular filtration rate was observed in hyperthyroid rats when data were expressed per gram kidney weight, but glomerular filtration rate was similar to that of control rats when normalized by body weight. 4. The shift in the pressure-diuresis-natriuresis response of hyperthyroid rats is mainly due to an increase in tubular reabsorption. Blunting of the renal pressure-diuresis-natriuresis mechanism in hyperthyroid rats may represent the functional resetting of the kidney necessary for sustained hypertension. However, a normal pressure-natriuresis response was observed in hypothyroid rats, in which blood pressure was markedly reduced.

Renal perfusion pressure and renin secretion in bilaterally renal denervated sheep.

To further investigate the influence of renal nerves on renin secretion, the renin secretion responses to step reductions of renal perfusion pressure (RPP) were studied in conscious sheep with innervated kidneys (n = 5) and with bilaterally denervated kidneys (n = 5). The average basal level of RPP in sheep with denervated kidneys (82 +/- 4 mmHg; 1 mmHg = 133.3 Pa) was similar to that in sheep with innervated kidneys (83 +/- 3 mmHg). RPP was reduced in four sequential 15-min steps, to a final level of 54 +/- 2 mmHg in sheep with innervated kidneys and to 57 +/- 1 mmHg in denervated sheep. The renin secretion rate was increased as RPP was reduced in sheep with innervated kidneys. Baseline peripheral plasma renin activity was reduced and there was almost no response of renin secretion rate to reduction of RPP in sheep with denervated kidneys. Also, baseline renal blood flow, urine flow rate, sodium excretion rate, and potassium excretion rate were higher in sheep with denervated kidneys than those with innervated kidneys. Baseline plasma angiotensin II was similar in both groups of sheep. As RPP was decreased, plasma angiotensin II was increased in sheep with innervated kidneys, but was not RPP or renal denervation. In conclusion, hormonal factors, such as angiotensin II and atrial natriuretic factor, do not account for the dramatic suppression of renin secretion in response to the reduction of RPP in sheep with bilateral renal denervation. Renal nerves are a necessary component in the control of renin secretion during reduction of RPP and may contribute to the regulation of baseline plasma renin activity and sodium excretion rate in conscious ewes.

Influences of renal nerves and pregnancy on renin secretion in sheep

To investigate the role of the renal nerves in the control of renin secretion during pregnancy, we prepared sheep with one denervated kidney, bilateral renal vein catheters, and an inflatable aortic occluder. The renin secretory responses to step reductions of renal perfusion pressure (RPP) of the innervated and denervated kidneys were compared in eight nonpregnant and nine pregnant (115-130 days gestation) sheep in a normal conscious state. Nonpregnant sheep had average basal levels of mean arterial pressure (MAP) of 91 +/- 3 mmHg, plasma renin activities (PRA) of 2.3 +/- 0.4 ng ANG I.ml-1.3 h-1, and plasma angiotensin (ANG) concentrations of 8.4 +/- 1.1 pg/ml. Pregnant sheep had reduced levels (P < 0.01) of MAP (76 +/- 3 mmHg) but elevated levels of PRA (3.8 +/- 0.4 ng ANG I.ml-1.h 3-1; P < 0.5) and ANG II (12.0 +/- 1.6 pg/ml; P = 0.08). Four successively reduced levels of RPP were observed for 15 min each in both groups of sheep. In both groups, RPP was reduced to a final level of 51 +/- 2 mmHg. The renal venous-arterial difference of PRA (v-aPRA) from the innervated kidneys was increased as RPP was reduced. However, there was little response of v-aPRA to RPP in denervated kidneys. In nonpregnant sheep, the relationship between RPP and renin secretion rate was characterized by an initially slow phase, over which small reductions of RPP resulted in small increases in renin secretion. As RPP fell, this relationship became progressively steeper in nonpregnant ewes.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormal pressure natriuresis in the dog model of obesity-induced hypertension.

Obesity is considered to be a major factor in the pathogenesis of hypertension in industrialized countries. Recent studies have suggested that the kidneys may play an important role in the development of obesity-induced hypertension. The purpose of this study was to determine whether obesity-induced hypertension is associated with abnormalities in the pressure-natriuresis relation. Renal function studies were performed in anesthetized control dogs (body weight, 20.2 +/- 0.8 kg) and obese dogs (body weight, 26.4 +/- 0.7 kg) that were maintained on a high-fat diet for 5 to 6 weeks. Mean arterial pressure averaged 122 +/- 5 mm Hg in the control group (n = 6) and 148 +/- 7 mm Hg in the obese group (n = 8). The effects of renal perfusion pressure on renal hemodynamics as well as sodium and water excretions were examined at five levels of renal perfusion pressure ranging from 75 to 165 mm Hg. Pressure-natriuretic and diuretic responses were reduced in the obese dogs by 40% to 50%. The renal blood flow and glomerular filtration rate autoregulatory responses and fractional lithium excretion responses to changes in renal perfusion pressure were similar in the control and obese dog groups. Associated with the attenuated natriuretic response to renal perfusion pressure in the obese dogs were significant elevations in plasma renin activity (4.3 +/- 1.6 versus 1.6 +/- 0.5 ng angiotensin I/mL per hour), plasma aldosterone concentration (34.4 +/- 6.4 versus 15.3 +/- 3.2 ng/dL), and plasma insulin concentration (30.5 +/- 6.8 versus 20.9 +/- 2.9 IU/mL).(ABSTRACT TRUNCATED AT 250 WORDS)

Pressure diuresis and natriuresis in cirrhotic rats

Arterial hypotension in liver cirrhosis has been proposed as a major mechanism contributing to renal sodium and water retention. To evaluate kidney excretory responses at different levels of arterial pressure (AP), we have characterized the relationships between renal perfusion pressure (RPP) and sodium and water excretion in carbon tetrachloride cirrhotic rats. Experiments were performed in anesthetized control (n = 9) and cirrhotic rats with (Asc, n = 6) and without ascites (Cir, n = 6) by mechanically adjusting vascular resistance in animals with renal denervation and infused with main systemic hormones. Control and Cir animals showed similar glomerular filtration rates (GFR), renal blood flows, hematocrits (Hct), and plasma proteins (PP). However, Hct, PP, and GFR were significantly lower in the Asc rats. For the same level of RPP, both cirrhotic groups excreted significantly less water and sodium than controls. Then, the pressure diuresis and natriuresis relationships of the Cir animals were significantly depressed, but those of the Asc animals were more reduced than those of the Cir rats. These results indicate that the cirrhotic kidney is not able to normally increase the sodium and water excretion in response to changes in AP. Intrarenal mechanisms, and not mainly RPP, are likely mediators of the renal alterations of liver cirrhosis.

Autoregulation of Renal Blood Flow During Ovine Pregnancy

Since the renal vasculature is vasodilated and the renal perfusion pressure (RPP) is reduced during pregnancy, the capacity to autoregulate renal blood flow (RBF) during pregnancy is unclear. Therefore, we assessed RBF auto-regulation in nonpregnant and pregnant sheep at RPP of 80, 75, 70, and 60 mmHg under control conditions, during amino acid infusion (SAP), and in sheep with nonfiltering kidneys in order to stress the normal feedback regulations of RBF. In nonpregnant animals, RBF was unchanged until RPP was reduced below 70 mmHg, but in pregnant animals the breakpoint occurred at 75-80 mmHg. The autoregulatory index (AI) was significantly higher in pregnant than in nonpregnant animals at all levels of RPP below 80 mmHg, indicating a greater impairment of RBF autoregulation during pregnancy. Amino acid infusion (SAP) elevated basal RBF similarly in all sheep and suppressed the autoregulatory curves of both groups, although to a greater extent in the pregnant sheep. Basal RBF was increased with nonfilte...

Influence of angiotensin II on pressure natriuresis and renal hemodynamics in volume-expanded rats

This study examined whether angiotensin II (ANG II) influences the pressure-natriuretic (PN) response by altering renal cortical or medullary hemodynamics. Studies were performed in Inactin-anesthetized rats that were acutely volume expanded to maintain plasma renin activity and ANG II levels in the physiological range. Neural influences on the kidney were eliminated by renal denervation, and plasma levels of norepinephrine, vasopressin, cortisol, and aldosterone were fixed by intravenous infusion. In control rats (n = 8), sodium excretion increased from 3 to 17 microeq.min-1.g kidney wt-1 as renal perfusion pressure (RPP) was elevated from 96 to 141 mmHg (n = 8). Captopril (2 mg/kg, n = 9) reduced plasma levels of ANG II from 48 +/- 5 to 18 +/- 2 pg/ml, but it did not alter the PN relationship. Infusion of ANG II (20 ng.kg-1.min-1, n = 9) increased plasma levels of ANG II to 232 +/- 42 pg/ml and shifted the PN relationship to the right by 14 mmHg. Captopril increased renal blood flow, and infusion of ANG II returned it to control. Captopril had no effect on glomerular filtration rate (GFR) or glomerular capillary pressure (Pglom); however, subsequent ANG II infusion decreased Pglom from 56 +/- 2 to 48 +/- 2 mmHg and reduced GFR by 30%. Neither captopril nor ANG II altered papillary bloodflow or vasa recta capillary pressure at normal levels of RPP. These results indicate that the shift of the PN relationship during infusion of ANG II is due to a decrease in filtered load and enhanced tubular reabsorption of sodium. Acute blockade of the renin-angiotensin system had little effect on the PN response in volume-expanded rats despite affecting renal hemodynamics, because either the plasma and/or intrarenal levels of ANG II were already suppressed below those needed to influence tubular function or volume expansion inhibits tubular reabsorption in the nephron segments normally influenced by ANG II.

Stimulation of renin release by hyperkalemia in the nonfiltering kidney

This study was designed to analyze the acute effects of hyperkalemia on renin release in the normal filtering kidney and the nonfiltering kidney. Plasma K was increased by acute intravenous KCl infusion. In the normal filtering kidney experiment plasma K was 5.7 vs. 3.5 meq/l. Hyperkalemia resulted in a 45% increase in renal blood flow (RBF) and a 35% increase in glomerular filtration rate (GFR) at the 120-mmHg pressure level. Renin release was significantly greater in the hyperkalemic group than in the control group (P less than 0.01) with the greatest effect over the lower pressure range. In the nonfiltering kidney experiment plasma K was 6.09 vs. 3.5 meq/l. RBF was 33% greater in the hyperkalemic than in the normokalemic group at the 130-mmHg pressure level. Renin release was also greater in the hyperkalemic group than in the normokalemic group (P less than 0.01). However, unlike the normal filtering kidney experiments, in the nonfiltering kidneys the difference in renin release was most prominent at the highest level of renal perfusion pressure. These experiments demonstrate that acute hyperkalemia can cause renal vasodilation and stimulate renin release in both filtering and nonfiltering kidney preparations and that potassium may affect renin release both through a direct effect on the juxtaglomerular cells and indirectly by affecting delivery of fluid and/or NaCl to the macula densa.

Regulation of renin release and renal hemodynamics during acute and chronic verapamil administration

The effects of short- and long-term administration of the calcium-entry blocker verapamil on regulation of renal hemodynamics and renin release were analyzed in anesthetized dogs at controlled levels of renal perfusion pressure between 110 and 60 mmHg. The following three groups of dogs were studied: a control group, an acutely treated verapamil group (initial dose of 150 micrograms/kg followed by 4 micrograms.kg-1.min-1), and a chronically treated verapamil group (240 mg per os twice each day). At 110 mmHg the renal blood flow (RBF) in the acutely and chronically treated groups was 53% greater than (P less than 0.03) and 79% greater than (P less than 0.01) that of the control group. Glomerular filtration rate (GFR) in the acutely and chronically treated groups was 64 and 92%, respectively, greater than (P less than 0.01 for both) that of the control group. Autoregulation of RBF and GFR was extremely effective in the control group, whereas it was severely impaired by acute and long-term treatment with verapamil. Renin release at 110 mmHg in the control and the acutely treated groups were similar, 3.36 +/- 0.96 and 4.46 +/- 0.64 U.min-1.g-1, respectively, although in the chronically treated group the rate of release was 8.89 +/- 2.60 U.min-1.g-1 (P less than 0.03). As perfusion pressure was reduced, the rate of release from the acutely treated group rose to higher levels than that of the control group; at 70 mmHg release from the acutely treated group was 88% greater than that of the control group (P less than 0.01). Verapamil profoundly alters regulation of renal hemodynamics and renin release and the effect is prominent during both short- and long-term administration.

Atrial natriuretic peptide and pressure natriuresis: interactions with the renin-angiotensin system

The aim of this study was to quantitate the effects of increases in atrial natriuretic peptide (ANP), within the pathophysiological range, on the acute pressure natriuresis mechanism and the role of the renin-angiotensin system (RAS) in modulating these effects. Renal hemodynamics and electrolyte excretion were measured in anesthetized dogs while renal perfusion pressure (RPP) was controlled at three levels (120-122, 100, and 75 mmHg) with and without intrarenal infusion of ANP at 5 ng.kg-1.min-1. Sodium excretion was significantly higher during ANP infusion at RPP of 122 +/- 3 mmHg, averaging 55.8 +/- 13.7 during control and 113.3 +/- 23.3 mueq/min during ANP infusion. AT RPP of 101 +/- 1 mmHg, sodium excretion was 51.8 +/- 17.4 during control and 93.0 +/- 17.6 mueq/min during ANP infusion, but at RPP of 75 +/- 0 mmHg there was no difference in sodium excretion between control and ANP infusion. In a second set of dogs, angiotensin II (ANG II) formation was blocked with captopril (20 micrograms.kg-1.min-1), circulating (5 ng.kg-1.min-1), and the above protocol was repeated. When the RAS was fixed, the renal responses to ANP infusion were abolished, even at the higher pressure levels. These data indicate that ANP increases the slope of pressure natriuresis; at higher levels of RPP, ANP potentiates pressure natriuresis but not at lower pressures. In addition, part of this effect may be due to suppression of the RAS, because the ANP-induced shift in the pressure natriuresis relationship was abolished when circulating ANG II was maintained constant.