scholarly journals Endothelin induces diuresis and natriuresis in the rat by acting on proximal tubular cells through a mechanism mediated by lipoxygenase products.

1991 ◽  
Vol 2 (1) ◽  
pp. 57-69
Author(s):  
N Perico ◽  
R P Cornejo ◽  
A Benigni ◽  
B Malanchini ◽  
J R Ladny ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Atrial Natriuretic Peptide ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Lipoxygenase Products ◽  
Natriuretic Effect

Besides being a potent renal vasoconstrictor, endothelin causes diuresis and natriuresis. At which site along the nephron and how endothelin alters water and sodium handling in the tubule remain to be clarified. It was found that endothelin (75 pmol) given as an i.v. infusion in vivo to rats caused diuresis and urinary sodium excretion to double but did not affect glomerular filtration rate and renal plasma flow. On raising the dose of endothelin to 150 pmol, a further increase in diuresis and natriuresis was found, whereas glomerular filtration rate fell 33% and renal plasma flow fell 36%; 300 pmol of endothelin reduced glomerular filtration rate by 73% and renal plasma flow by 77% but did not significantly affect diuresis and absolute sodium excretion. It did, however, increase fractional sodium excretion eightfold. Lithium clearance studies of changes in tubular handling of water and sodium indicated that infusion of 150 pmol of endothelin to rats caused a reduction in absolute (pre, 84.7 +/- 5.9; post, 47.9 +/- 6.1 microEq/min/100 g) and fractional (pre, 85.7 +/- 3.0; post, 64.7 +/- 6.4%) proximal reabsorption of sodium. Endothelin infusion (150 pmol) was not associated with any significant change in plasma atrial natriuretic peptide levels, which on average remained comparable to those in rats given the vehicle alone (49.7 +/- 8.4 versus 46.3 +/- 5.6 pg/mL). In the isolated perfused rat kidney preparation, exposure to 150 pmol of endothelin significantly increased fractional sodium excretion over preinjection values (pre, 2.2 +/- 0.2; post, 7.3 +/- 1.0%) despite a marked decrease in glomerular filtration rate and renal perfusate flow. Additional in vivo experiments showed that oral administration of the specific 5-lipoxygenase inhibitor L-651,392 to rats prevented the increase in urine flow rate (pre, 5.7 +/- 0.1; post, 6.6 +/- 0.8 microL/min), and in absolute (pre, 0.33 +/- 0.04; post, 0.37 +/- 0.05 microEq/min) and fractional (pre, 0.10 +/- 0.02; post, 0.11 +/- 0.03%) sodium excretion caused by bolus i.v. infusion of endothelin (150 pmol). Similarly, a specific leukotriene C4/D4 receptor antagonist, L-649,923, also prevented the diuretic and natriuretic effect of 150 pmol of endothelin i.v. infusion. These findings show that (1) endothelin has a diuretic and natriuretic effect that is independent of its action on renal hemodynamics; (2) this effect depends on a direct action on the proximal tubules; (3) atrial natriuretic peptide does not appear to be involved in this effect; and (4) the diuretic and natriuretic responses to endothelin are mediated by 5-lipoxygenase products.

Angiotensin II modulates the intrarenal effects of atrial natriuretic peptide

1988 ◽  
Vol 255 (3) ◽  
pp. F545-F551
Author(s):  
H. M. Siragy ◽  
N. E. Lamb ◽  
C. E. Rose ◽  
M. J. Peach ◽  
R. M. Carey
Keyword(s):  
Glomerular Filtration Rate ◽  
Angiotensin Ii ◽  
Atrial Natriuretic Peptide ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Systemic Effects ◽  
Ang Ii ◽  
Renal Effects

The mechanism by which atrial natriuretic peptide (ANP) increases renal water and solute excretion is not fully understood. We studied the renal effects of ANP and angiotensin II (ANG II) separately and together in uninephrectomized conscious dogs (n = 7) in sodium metabolic balance (80 meq/day). Exogenous ANG II and ANP were without measurable systemic effects as demonstrated by absence of changes in blood pressure, plasma aldosterone concentration, and plasma renin activity. The quantity of ANG II that had significant renal effects that were without measurable systemic effects was 0.2 pmol.kg-1.min-1. Three infusion rates of ANP had significant renal effects (1, 10, and 20 pmol.kg-1.min-1). These quantities of ANP caused significant diuresis, natriuresis, kaliuresis, and increased glomerular filtration rate without significant changes in renal plasma flow. ANG II alone caused significant antidiuresis, antinatriuresis, and decreased glomerular filtration rate and renal plasma flow. When ANG II and ANP were given together, no change in urinary flow rate, urinary sodium or potassium excretion, or renal plasma flow was observed, whereas glomerular filtration rate increased. Filtration fraction increased significantly with ANG II and ANP separately and together. Intrarenal ANP prevents the ANG II-induced decrement in urinary sodium excretion and urine flow rate. ANP may play an important role in escape from the sodium-retaining action of intrarenal ANG II.

scholarly journals Augmented cyclooxygenase-2 effects on renal function during varying states of angiotensin II

2010 ◽  
Vol 299 (5) ◽  
pp. F954-F962 ◽  
Author(s):  
Torrance Green ◽  
Jorge Rodriguez ◽  
L. Gabriel Navar
Keyword(s):  
Blood Flow ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Ang Ii ◽  
Series Of Experiments ◽  
Cox 2

Nonsteroidal anti-inflammatory drug usage has long revealed renoprotective prostaglandin actions on the renal microvasculature during increased pressor hormone influence, but whether increased cyclooxygenase (COX)-2 expression supports prostaglandin vasodilatory influence by interfering with the actions of ANG II remains unresolved. Therefore, we tested the hypothesis that COX-2 inhibition causes hemodynamic and excretory effects that are increased in proportion to ANG II activity. In anesthetized Sprague-Dawley rats having augmented cortical COX-2 expression but different ANG II activity, we conducted renal clearance experiments during acute inhibition of COX-2 with nimesulide (NMSLD) and inhibition of COX-1 with SC-560. In one series of experiments, acute captopril [acute angiotensin-converting enzyme (ACE) inhibitor (aACEi)] was administered alone ( n = 13) or in combination with chronic captopril [chronic ACEi (cACEi)] pretreatment ( n = 19). In another series of experiments, rats were fed a normal-sodium [0.4% (NS), n = 12] or a low-sodium [0.03% (LS), n = 18] diet. NMSLD did not alter mean arterial blood pressure in any group but, in the LS and cACEi groups, decreased renal plasma flow (from 3.99 ± 0.33 to 2.85 ± 0.26 and from 4.30 ± 0.19 to 3.22 ± 0.21 ml·min−1·g−1), cortical blood flow (−12 ± 8% and −13 ± 4%), and glomerular filtration rate (from 0.88 ± 0.04 to 0.65 ± 0.05 and from 0.95 ± 0.07 to 0.70 ± 0.05 ml·min−1·g−1). In contrast, medullary blood flow (MBF) was significantly decreased by COX-2 inhibition in NS (−24 ± 5%), LS (−27 ± 8%), aACEi (−16 ± 3.8%), and cACEi (−24 ± 4.2%) groups. Absolute and fractional sodium excretion rates were unchanged by NMSLD, except in the LS group (0.75 ± 0.05 μeq/min and 0.43 ± 0.15% and 0.51 ± 0.06 μeq/min and 0.26 ± 0.10%). SC-560 did not augment the effects of NMSLD. These results demonstrate an augmented COX-2-mediated vasodilation that is not contingent on ANG II, in contrast to COX-2-mediated augmented sodium excretion, where ANG II activity is requisite. Furthermore, the COX-2 effects on MBF are not contingent on ANG II or changes in cortical microvascular responses. These results reflect COX-2 continual regulation of MBF and adaptive opposition to ANG II prohypertensinogenic effects on renal plasma flow, cortical blood flow, glomerular filtration rate, and absolute and fractional sodium excretion.

Differential effect of T-type voltage-gated Ca2+ channel disruption on renal plasma flow and glomerular filtration rate in vivo

2014 ◽  
Vol 307 (4) ◽  
pp. F445-F452 ◽  
Author(s):  
Anne D. Thuesen ◽  
Henrik Andersen ◽  
Majken Cardel ◽  
Anja Toft ◽  
Steen Walter ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Flow ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Voltage Gated

Voltage-gated Ca2+ (Cav) channels play an essential role in the regulation of renal blood flow and glomerular filtration rate (GFR). Because T-type Cav channels are differentially expressed in pre- and postglomerular vessels, it was hypothesized that they impact renal blood flow and GFR differentially. The question was addressed with the use of two T-type Cav knockout (Cav3.1−/− and Cav3.2−/−) mouse strains. Continuous recordings of blood pressure and heart rate, para-aminohippurate clearance (renal plasma flow), and inulin clearance (GFR) were performed in conscious, chronically catheterized, wild-type (WT) and Cav3.1−/− and Cav3.2−/− mice. The contractility of afferent and efferent arterioles was determined in isolated perfused blood vessels. Efferent arterioles from Cav3.2−/− mice constricted significantly more in response to a depolarization compared with WT mice. GFR was increased in Cav3.2−/− mice with no significant changes in renal plasma flow, heart rate, and blood pressure. Cav3.1−/− mice had a higher renal plasma flow compared with WT mice, whereas GFR was indistinguishable from WT mice. No difference in the concentration response to K+ was observed in isolated afferent and efferent arterioles from Cav3.1−/− mice compared with WT mice. Heart rate was significantly lower in Cav3.1−/− mice compared with WT mice with no difference in blood pressure. T-type antagonists significantly inhibited the constriction of human intrarenal arteries in response to a small depolarization. In conclusion, Cav3.2 channels support dilatation of efferent arterioles and affect GFR, whereas Cav3.1 channels in vivo contribute to renal vascular resistance. It is suggested that endothelial and nerve localization of Cav3.2 and Cav3.1, respectively, may account for the observed effects.

Effects of a kinin antagonist on renal function in rats

1990 ◽  
Vol 258 (3) ◽  
pp. F643-F648
Author(s):  
M. Nakagawa ◽  
J. M. Stewart ◽  
R. J. Vavrek ◽  
A. Nasjletti
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Combined Treatment ◽  
Neutral Endopeptidase ◽  
Kinin Receptor

We contrasted the effects of D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-DPhe-Thi-Arg-TFA (kinin receptor antagonist), of aprotinin (kallikrein inhibitor), and of combined treatment with captopril (kininase II inhibitor) and phosphoramidon (neutral endopeptidase 24.11 inhibitor) on renal function of rats with and without 14-day deoxycorticosterone pretreatment (DOC, 25 mg.kg-1.wk-1 sc). Neither the kinin antagonist nor aprotinin affected renal function in rats with and without DOC pretreatment. Combined treatment with captopril and phosphoramidon caused in rats with and without DOC pretreatment augmentation (P less than 0.05) of kinin excretion (50-64%), glomerular filtration rate (12-11%), and sodium excretion (46-48%). In DOC-pretreated rats undergoing infusion of captopril and phosphoramidon, the superimposed administration of either the kinin antagonist or aprotinin caused the lowering of renal plasma flow, glomerular filtration rate, and sodium excretion. These effects of the kinin antagonist and aprotinin in rats infused with kininase inhibitors may be the consequence of blockade, respectively, of the renal actions and synthesis of kinins that, when in excess, elicit renal vasodilation and increase glomerular filtration rate and sodium excretion. Collectively, these observations suggest regulatory influence of kinins during conditions featuring increased renal kinin levels.

Effect of Serotonin on Renal Hemodynamics and Sodium Excretion in the Dog

1958 ◽  
Vol 193 (3) ◽  
pp. 639-643 ◽  
Author(s):  
William P. Blackmore
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Sodium Excretion ◽  
Filtration Rate ◽  
Direct Action ◽  
Renal Plasma Flow ◽  
Specific Effect ◽  
Arterial Blood ◽  
Change In Mean

The effects of constant intravenous infusion of serotonin with doses of 5 and 10 µg/kg/min. on glomerular filtration rate, effective renal plasma flow, urine flow and sodium excretion were studied in trained, unanesthetized female dogs. A small but significant decrease in glomerular filtration rate associated with increased renal plasma flow occurred at the 5 µg/kg/min. dose indicating a specific effect of serotonin on the kidney. Similar changes were noted with the 10 µg/kg/min. dose plus a marked antidiuretic effect that occurred in the absence of any significant change in mean arterial blood pressure and an intact neurohypophysis indicating a direct action on water reabsorption in the kidney. Urinary sodium excretion decreased with both doses as a result of a decline in glomerular filtration rate associated with increased tubular reabsorption. These results indicate that serotonin has a specific effect on the kidney and suggest that this substance may alter the caliber of the glomerular vessels to decrease renal vascular resistance.

Atrial extracts increase glomerular filtration rate in vivo

1985 ◽  
Vol 248 (1) ◽  
pp. F24-F30 ◽  
Author(s):  
D. Beasley ◽  
R. L. Malvin
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Recovery Period ◽  
Plasma Renin ◽  
Urine Flow ◽  
Constant Infusion ◽  
Natriuretic Effect

We measured the effect of a constant infusion of rat atrial extract on the glomerular filtration rate (GFR), renal plasma flow (RPF), and plasma renin concentration (PRC) of bioassay rats. The infusion rate of the atrial extract was 0.038 ml/min, which represented 1.25 mg of homogenized atrial tissue/min. To ensure that dead space was cleared, clearance measurements during the atrial extract infusion were not begun until urine flow had increased and 300 microliter of urine had been excreted. In the first series of rats, control GFR was 0.69 +/- 0.05, increased to 1.04 +/- 0.06 during infusion of atrial extract, and then decreased to 0.72 +/- 0.08 ml X min-1 X 100 g-1 during the recovery period. In a second series, RPF was also measured. GFR increased from 0.92 +/- 0.02 to 1.15 +/- 0.05 ml X min-1 X 100 g-1, while RPF was unchanged. In both series, the increase in GFR was statistically significant. Constant infusion of atrial extracts had no significant effect on PRC. These studies provide evidence that an atrial factor can cause a large increase in GFR, which may contribute to the natriuretic effect of atrial extracts.

Clinical Renal Function Testing by External Double Isotope Monitoring Technique

1971 ◽  
Vol 10 (01) ◽  
pp. 16-24
Author(s):  
J. Fog Pedersen ◽  
M. Fog Pedersen ◽  
Paul Madsen
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Correlation Coefficients ◽  
Feedback System ◽  
Effective Renal Plasma Flow ◽  
Advantages And Disadvantages

SummaryAn accurate catheter-free technique for clinical determination simultaneouslyof glomerular filtration rate and effective renal plasma flow by means of radioisotopes has been developed. The renal function is estimated by the amount of radioisotopes necessary to maintain a constant concentration in the patient’s blood. The infusion pumps are steered by a feedback system, the pumps being automatically turned on when the radiation measured over the patient’s head falls below a certain preset level and turned off when this level is again readied. 131I-iodopyracet was used for the estimation of effective renal plasma flow and125I-iothalamate estimation of the glomerular filtration rate. These clearances were compared to the conventional bladder clearances and good correlation was found between these two clearance methods (correlation coefficients 0.97 and.90 respectively). The advantages and disadvantages of this new clearance technique are discussed.

Influence of nifedipine on cyclosporin A nephrotoxicity after unilateral nephrectomy in the spontaneously hypertensive rat

1991 ◽  
Vol 81 (2) ◽  
pp. 271-279 ◽  
Author(s):  
P. G. McNally ◽  
F. Baker ◽  
N. Mistry ◽  
J. Walls ◽  
J. Feehally
Keyword(s):  
Body Weight ◽  
Glomerular Filtration Rate ◽  
Renal Impairment ◽  
Cyclosporin A ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Denervation ◽  
Renal Plasma Flow ◽  
Spontaneously Hypertensive

1. Nifedipine ameliorates cyclosporin A-induced renal impairment in surgically intact (two-kidney) rats. This study investigates the effect of nifedipine on cyclosporin A nephrotoxicity in spontaneously hypertensive rats after either uninephrectomy or uninephrectomy with contralateral renal denervation. 2. Fourteen days after uninephrectomy pair-fed rats were injected for 14 days with cyclosporin A (25 mg/kg body weight) via the subcutaneous route and with nifedipine (0.1 mg/kg body weight) via the intraperitoneal route. Renal and systemic haemodynamics were measured in conscious unrestrained rats. 3. Whole-blood levels of cyclosporin A did not differ between groups (overall 352 ± 22 ng/ml, means ± sem). After uninephrectomy, cyclosporin A decreased the glomerular filtration rate (olive oil versus cyclosporin A: 0.96 ± 0.04 versus 0.70 ± 0.06 ml min−1 100 g body weight, P < 0.02) and effective renal plasma flow (1.94 ± 0.10 versus 1.38 ± 0.13, P < 0.01), and increased renal vascular resistance {(20.2 ± 1.8) × 104 versus (31.6 ± 3.3) × 104 kPa l−1 s [(20.2 ± 1.8) × 103 versus (31.6 ± 3.3) × 103 dyn s cm−5], P < 0.02} and mean arterial pressure (146.7 ± 6.7 versus 167.3 ± 2.9 mmHg, P < 0.05). Neither renal denervation nor nifedipine prevented the reduction in glomerular filtration rate or effective renal plasma flow induced by cyclosporin A. 4. This study infers that the sympathetic nervous system does not play an active role in cyclosporin A nephrotoxicity and demonstrates that the concomitant administration of nifedipine to rats with reduced renal mass does not ameliorate cyclosporin A-induced renal impairment.

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