Inhibition of platelet-activating factor induced renal hemodynamic and tubular dysfunctions with L-655,240, a new thromboxane–prostaglandin endoperoxide antagonist

1989 ◽  
Vol 67 (4) ◽  
pp. 304-308 ◽  
Author(s):  
R. L. Hébert ◽  
P. Sirois ◽  
G. E. Plante
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Platelet Activating Factor ◽  
Urinary Sodium ◽  
Dependent Manner ◽  
Prostaglandin Endoperoxide

The continuous infusion or bolus injection of the platelet-activating factor (PAF) is associated with profound hypotension, marked reductions of renal plasma flow, glomerular filtration, and urinary sodium excretion. All these effects are inhibited by blocking PAF receptors. To examine further the potential mediators of PAF on renal function, we utilized L-655,240 (6 mg/kg, intravenously), a thromboxane–prostaglandin endoperoxide antagonist, to study the systemic and renal response to PAF (0.8 μg/kg, intravenously) in the anesthetized dog, using clearance methodology. PAF decreased blood pressure from 115 ± 7 to 54 ± 4 mmHg (1 mmHg = 133.3 Pa), renal plasma flow from 105 ± 6 to 74 ± 56 mL/min, and glomerular filtration from 43 ± 3 to 32 ± 1 mL/min. PAF also reduced urine volume from 1.1 ± 0.2 to 0.4 ± 0.1 mL/min, and urinary sodium from 158 ± 7 to 86 ± 7 μequiv./min. L-655,240 alone had no significant effect on blood pressure, renal plasma flow, and filtration rate, at any dose. However, the 6-mg/kg dose resulted in a slight elevation of diuresis, from 1.1 ± 0.2 to 1.9 ± 0.1 mL/min, and urinary sodium, from 134 ± 13 to 212 ± 19 μequiv./min. All doses of L-655,240 blocked the effect of PAF on blood pressure. However, the two lower doses of this antagonist (1 and 3 mg/kg) failed to prevent the PAF-induced fall of renal plasma flow and filtration rate, and attenuated the effect on urinary sodium in a dose-dependent manner. These results indicate that the renal vasoconstriction and antinatriuretic effects of PAF are probably mediated by thromboxane A2 and (or) prostaglandin endoperoxides in the dog. L-655,240 represents therefore a potent inhibitor of PAF-induced renal dysfunctions, and may be of significant interest to explore further the physiology and pathophysiology of PAF.Key words: platelet-activating factor, renal function, lipid mediators, thromboxane antagonist, shock.

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.

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.

Glomerular filtration and renal plasma flow during hyperthermia

1960 ◽  
Vol 198 (5) ◽  
pp. 1044-1048 ◽  
Author(s):  
G. S. Kanter
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Glomerular Filtration ◽  
Plasma Volume ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Control Value ◽  
Acid Clearance ◽  
Anesthetized Dogs

The purpose of this study was to investigate the factors that determine the direction and magnitude of the alteration in GFR (glomerular filtration rate) and RPF (renal plasma flow) in hyperthermia. The investigation was conducted on anesthetized dogs. Creatinine clearance was used as a measure of GFR and para-aminohippuric acid clearance was used as a measure of RPF. The GFR in 12 mildly dehydrated dogs went from a control value of 68.4 ± 4.5 ml/min. at RT (rectal temperature) of 38.9°C to a GFR of 25.1 ± 8.5 ml/min. at a RT of 42.1°C at the end of 5 hours of exposure to heat. Final dehydration averaged –2.0% body weight. The fall in GFR and RPF was not due to dehydration for in a group of six hydrated dogs (+4% body wt. at end) similar results were obtained. No decrease in GFR or RPF occurred in either hydrated or dehydrated dogs until severe hyperthermia (> 41.2°C) was present. Though there was a decline in blood pressure towards the end of each experiment, in both groups, the decrease in GFR and RPF preceded any marked fall in pressure. Both groups showed an increase in hematocrit and a decrease in plasma volume (measured by T-1824 dilution) which became marked at the end of 5 hours of exposure to heat. The decrease in GFR and RPF appears directly related to the hyperthermia for upon rapid cooling GFR and RPF increases towards normal in spite of the persisting decreased blood pressure and plasma volume and increased hematocrit.

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.

Effects of X-Irradiation on Renal Function of Rats

1957 ◽  
Vol 188 (2) ◽  
pp. 367-370 ◽  
Author(s):  
L. H. Smith ◽  
W. R. Boss
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Urine Flow ◽  
Whole Body ◽  
Irradiation Damage ◽  
X Rays

In a study of the direct effects of irradiation on the renal function of rats whose exteriorized kidneys were exposed to massive doses of x-rays, significant augmentation of the urine flow was observed 28 days after 2500 r. On the 7th day after 2500, 3000 and 4000 r the urine flow was slightly above that of control rats. The glomerular filtration rate was enhanced on the 7th day after 2500 and 3000 r. Conversely, 28 days after these x-ray doses the filtration rate was slightly below the control values. In the 4000-r, 28-day group, the glomerular filtration rate was 43% below that of the controls. No significant changes in the renal plasma flow occurred on the 7th day after 2500, 3000 and 4000 r. An insignificant increase in the renal plasma flow was noted 28 days after 2500 and 3000 r. On the 28th day after 4000 r, however, the renal plasma flow was 51% below that of the controls. We concluded that both augmentation and depression of renal function were the result of the direct action of x-rays on the kidneys. The results also suggest that renal failure resulting from direct irradiation damage to the kidneys is not a major factor that contributes to deaths occurring within 7 days after the exposure of rats to 4000 r or less of whole-body x-rays.

Effects of High- and Low-Osmolar Contrast Media on Renal Plasma Flow and Glomerular Filtration Rate in Euvolaemic and Dehydrated Rats

1989 ◽  
Vol 30 (4) ◽  
pp. 383-389 ◽  
Author(s):  
A. Nygren ◽  
H. R. Ulfendahl ◽  
A. Fasching
Keyword(s):  
Renal Function ◽  
Body Weight ◽  
Glomerular Filtration Rate ◽  
Adverse Effects ◽  
Contrast Media ◽  
Glomerular Filtration ◽  
Intravenous Injection ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow

The effects of a slow intravenous injection of contrast media (CM) on renal function and haemodynamics were investigated in euvolaemic and dehydrated rats. Iodine-equivalent doses (1600 mg I/kg body weight) of ioxithalamate, ioxaglate, iopamidol and iohexol were used. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were assessed with clearance techniques. In euvolaemic rats no statistically significant decrease in GFR or RPF was found after CM injections. In the dehydrated rats the changes in GFR were more pronounced and this was significantly decreased in the ioxithalamate and iopamidol groups while RPF was still not decreased. This study indicates that dehydration potentiates adverse effects of CM on GFR and that there may be differences between the effects of low-osmolar and high-osmolar CM on GFR and also between different low-osmolar CM.

scholarly journals SERIAL RENAL CLEARANCES IN DOGS WITH NEPHROGENIC AND SPONTANEOUS HYPERTENSION

1949 ◽  
Vol 90 (6) ◽  
pp. 511-524 ◽  
Author(s):  
J. Stamler ◽  
L. N. Katz ◽  
S. Rodbard
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Kidney Function ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Spontaneous Hypertension ◽  
Focal Lesions ◽  
Renal Clearances

Evidence is presented on the occurrence of spontaneous hypertension in dogs. All dogs with spontaneous hypertension exhibited normal renal plasma flow and glomerular filtration rate. Clearances on nephrogenic hypertensive dogs revealed that some exhibited normal kidney function, while others had significant depression of renal plasma flow and glomerular filtration rate. In the latter, the filtration fraction may or may not be elevated. Serial renal clearances were done at intervals on 3 dogs with spontaneous hypertension during their 3rd year of known hypertension. They exhibited no tendency to develop impaired renal function in the face of prolonged benign hypertension. Serial renal clearances on nephrogenic hypertensive dogs revealed no tendency for kidney function to become progressively impaired. This was true, whether the immediate postoperative clearance values were normal or depressed. It was also true regardless of the duration of the hypertension. It is suggested that mechanisms other than elevated blood pressure per se operate to produce progressive kidney damage and impairment of renal function. No tendency was revealed over the course of a year or more for the kidney function to improve in Goldblatt dogs exhibiting depressed clearances immediately postoperatively. This is interpreted as evidence against the postoperative development in persistently hypertensive Goldblatt dogs of a renal collateral circulation sufficient to augment significantly effective renal blood flow. Pathological studies on 2 dogs with spontaneous hypertension revealed slight to moderate chronic focal lesions in the kidneys, and bilateral adrenal cortical adenomatous hyperplasia. Both lesions may have no pathogenetic significance. In accord with previous observations, autopsies on 3 Goldblatt dogs revealed minimal renal changes in one, and unilateral kidney atrophy with contralateral hypertrophy in the 2 others. The adrenals were normal. In general, data on renal clearances showed correlation with postmortem kidney findings. However, normal renal clearances are found in the presence of anatomically abnormal kidneys. The findings in canine spontaneous and nephrogenic hypertension are compared and contrasted with data obtained in human essential hypertension. Pathogenetic relationships are discussed.

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