scholarly journals ETA receptor blockade attenuates the hypertension but not renal dysfunction in DOCA-salt rats

1998 ◽  
Vol 275 (1) ◽  
pp. R245-R252 ◽  
Author(s):  
Graham H. Allcock ◽  
Richard C. Venema ◽  
David M. Pollock
Keyword(s):  
Renal Function ◽  
Creatinine Clearance ◽  
Filtration Rate ◽  
Tap Water ◽  
Receptor Blockade ◽  
Salt Treatment ◽  
Excretory Function ◽  
Salt Hypertension ◽  
Eta Receptor ◽  
Food And Water Intake

Endothelin (ET)-1 has potent renal and systemic vasoconstrictor properties, and thus we investigated whether ET-1 plays a role in increasing blood pressure and decreasing renal function in DOCA-salt hypertension. After a right nephrectomy, rats had DOCA or placebo pellets implanted subcutaneously and were given saline or tap water to drink, respectively. Additional groups of rats were given the ETA receptor antagonist A-127722 in their water. Rats were maintained in metabolic cages for monitoring excretory function and food and water intake. Three weeks after surgery, mean arterial pressure (MAP) was recorded in the conscious rats via a carotid artery catheter. As expected, DOCA-salt rats had significantly higher MAP compared with uninephrectomized controls (197 ± 6 vs. 133 ± 3 mmHg). Creatinine clearance, used as an estimate of glomerular filtration rate, was significantly reduced in DOCA-salt rats (2.9 ± 0.4 vs. 6.8 ± 0.3 dl ⋅ day−1 ⋅ 100 g−1 body wt in controls). ETA receptor blockade with A-127722 significantly reduced MAP (156 ± 8 mmHg) but had no effect on creatinine clearance of DOCA-salt-treated rats (2.8 ± 0.3 dl ⋅ day−1 ⋅ 100 g−1 body wt). Plasma ET-1 levels were significantly raised after DOCA-salt treatment (1.4 ± 0.5 pg/ml vs. 0.4 ± 0.1 pg/ml in controls). A-127722 treatment increased circulating ET-1 levels in both placebo (2.3 ± 0.5 pg/ml) and DOCA-salt (5.6 ± 0.7 pg/ml) rats. However, ET-1 mRNA expression in renal cortical and medullary tissue was not affected by either A-127722 or DOCA-salt treatments. Thus ETA receptors appear to play a role in the maintenance and development of DOCA-salt hypertension but not in the accompanying reduction of renal function.

scholarly journals Inflammatory Mediators Release in Urine from Mice Injected withCrotalus durissus terrificusVenom

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
A. Hernández Cruz ◽  
L. Barbosa Navarro ◽  
R. Z. Mendonça ◽  
V. L. Petricevich
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Creatinine Clearance ◽  
Filtration Rate ◽  
Fractional Excretion ◽  
Renal Tissue ◽  
Total Proteins ◽  
Crotalus Durissus Terrificus ◽  
Inflammatory Status ◽  
Crotalus Durissus

In this study, we investigated in groups of female BALB/c mice injected withCrotalus durissus terrificusvenom (Cdt) the renal function based on creatinine clearance, percentage of fractional excretion cytokines and histological examination of renal tissue.Cdtcaused renal alterations that induced proteinuria during the initial hours post-venom and reduced creatinine clearance 15 min. up to 2 hours post-venom administration. In urine from mice injected withCdtinduced a decrease in IL-4 levels. More pronounced increments of IL-5, IL-6 and IFN-γwere observed after 15 and 30 min, respectively. The highest levels of TNF and IL-10 were observed at 1 and 4 hs, respectively. The ratios of pro- and anti-inflammatory cytokines in animals injected withCdt, which may be manifested in the inflammatory status during the envenoming. In groups of animals treated withCdtwere observed a decreasing in creatinine clearance and its effect on glomerular filtration rate was accompanied by decreased fractional excretion of cytokines and morphologic disturbances. This loss of change selectively in envenomation could thus explain why the relatively excretion of cytokines is reduced while of total proteins increases. In conclusion the fractional excretion of cytokines is significantly reduced in mice injected withCdt, despite proteinuria.

Assessment of renal function by inulin clearance: comparison with creatinine clearance as determined by enzymatic methods.

1989 ◽  
Vol 35 (2) ◽  
pp. 312-314 ◽  
Author(s):  
F S Apple ◽  
P Benson ◽  
P A Abraham ◽  
T G Rosano ◽  
C E Halstenson
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Creatinine Clearance ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
The Other ◽  
Inulin Clearance ◽  
Urinary Creatinine ◽  
Single Slide ◽  
Enzymatic Methods

Abstract We compared creatinine clearances determined by enzymatic (Kodak Ektachem 700 single-slide, Boehringer Mannheim creatinine PAP) and nonenzymatic (Jaffé, HPLC) methods with glomerular filtration rate measured by inulin clearance in patients with varying degrees of renal function. The Kodak enzymatic assay gave values for creatinine 2 to 3 mg/L higher than the other methods. This resulted in significantly lower creatinine clearances than inulin clearances and creatinine clearances determined by the other methods. However, correlations between all methods for serum and urinary creatinine values and clearances were good. To avoid between assay (enzymatic vs nonenzymatic) discrepancies, manufacturers should agree to an acceptable standard of calibration under the usual conditions used with patients.

scholarly journals DOCA-salt treatment enhances responses to endothelin-1 in murine corpus cavernosumThis article is one of a selection of papers published in the special issue (part 1 of 2) on Forefronts in Endothelin.

2008 ◽  
Vol 86 (6) ◽  
pp. 320-328 ◽  
Author(s):  
Fernando S. Carneiro ◽  
Fernanda R.C. Giachini ◽  
Victor V. Lima ◽  
Zidonia N. Carneiro ◽  
Kênia P. Nunes ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Tap Water ◽  
Corpus Cavernosum ◽  
Rho Kinase ◽  
Electrical Field Stimulation ◽  
Salt Treatment ◽  
Rho Kinase Inhibitor ◽  
Salt Hypertension ◽  
Selection Of ◽  
Added Salt

The penis is kept in the flaccid state mainly via a tonic activity of norepinephrine and endothelins (ETs). ET-1 is important in salt-sensitive forms of hypertension. We hypothesized that cavernosal responses to ET-1 are enhanced in deoxycorticosterone acetate (DOCA)-salt mice and that blockade of ETA receptors prevents abnormal responses of the corpus cavernosum in DOCA-salt hypertension. Male C57BL/6 mice were unilaterally nephrectomized and treated for 5 weeks with both DOCA and water containing 1% NaCl and 0.2% KCl. Control mice were uninephrectomized and received tap water with no added salt. Animals received either the ETA antagonist atrasentan (5 mg·day−1·kg−1 body weight) or vehicle. DOCA-salt mice displayed increased systolic blood pressure (SBP), and treatment with atrasentan decreased SBP in DOCA-salt mice. Contractile responses in cavernosal strips from DOCA-salt mice were enhanced by ET-1, phenylephrine, and electrical field stimulation (EFS) of adrenergic nerves, whereas relaxations were not altered by IRL-1620 (an ETB agonist), acetylcholine, sodium nitroprusside, and EFS of nonadrenergic noncholinergic nerves. PD59089 (an ERK1/2 inhibitor), but not Y-27632 (a Rho-kinase inhibitor), abolished enhanced contractions to ET-1 in cavernosum from DOCA-salt mice. Treatment of DOCA-salt mice with atrasentan did not normalize cavernosal responses. In summary, DOCA-salt treatment in mice enhances cavernosal reactivity to contractile, but not to relaxant, stimuli, via ET-1/ETA receptor-independent mechanisms.

ETA receptor blockade prevents hypertension associated with exogenous endothelin-1 but not renal mass reduction in the rat.

1997 ◽  
Vol 8 (7) ◽  
pp. 1054-1060
Author(s):  
D M Pollock ◽  
J S Polakowski
Keyword(s):  
Drinking Water ◽  
Arterial Pressure ◽  
Renal Mass ◽  
Tap Water ◽  
Receptor Activation ◽  
Receptor Blockade ◽  
Mass Reduction ◽  
Endothelin 1 ◽  
Eta Receptor ◽  
Series Of Experiments

The purpose of this study was to determine the effect of chronic ETA receptor blockade, using the orally active antagonist A-127722 in rats with reduced renal mass. The initial series of experiments was designed to characterize the effects of the ETA-selective antagonist A-127722 on arterial pressure and renal function when administered via drinking water over a 4-wk period. Male Sprague-Dawley rats were acclimated to metabolism cages, and baseline 24-h urine collections were obtained. A-127722 was placed in the drinking water at concentrations that delivered doses of 1 to 10 mg/kg per d. The compound had no effect on any of the variables measured, including arterial pressure, food and water intake, urine volume, and sodium and potassium excretion. In a separate group of rats, ETA receptor blockade was verified after 3 d of drinking water containing A-127722. Rats were anesthetized, a jugular vein catheter was inserted for infusions, and a femoral artery catheter was used for monitoring arterial pressure. The pressor response to intravenous injection of Big endothelin-1 (1 nmol/kg, intravenously) was inhibited by > 50% in rats given A-127722 at 10 mg/kg per d, which confirms the efficacy of A-127722 in blocking ETA-mediated responses when placed in drinking water. In an additional series of experiments, rats were anesthetized, the right kidney was removed, and two of three major branches of the left renal artery were ligated. After recovery, rats were returned to their cages and given A-127722 in the drinking water to deliver 1 or 10 mg/kg per d. Control rats underwent the same surgical procedures but were given tap water to drink. After 4 wk, rats that were treated with A-127722 developed similar increases in arterial pressure and urinary protein excretion as rats that received tap water. Therefore, although the ETA receptor antagonist A-127722 can inhibit ETA-mediated hypertension, it has no effect on hypertension produced by a reduction in renal mass. It is concluded that ETA receptor activation does not play a significant role in the functional derangements associated with renal mass reduction in the rat.

Assessment of renal function by serum creatinine and creatinine clearance: glomerular filtration rate estimated by four procedures.

1989 ◽  
Vol 35 (12) ◽  
pp. 2326-2330 ◽  
Author(s):  
F Van Lente ◽  
P Suit
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Serum Creatinine ◽  
Creatinine Clearance ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Wide Range ◽  
Clear Method ◽  
Serum And Urine

Abstract We compared creatinine concentrations in serum and urine and creatinine clearances determined by two Jaffé (Beckman's "Astra," Boehringer Mannheim Diagnostics) and two enzymatic (Kodak, Boehringer Mannheim Diagnostics) methods. Serum creatinine and creatinine clearances determined by each method were also compared with the glomerular filtration rate as measured with use of sodium [125I]iothalamate in patients with a wide range of renal function. Results between methods correlated excellently, but we saw clear method-dependent biases of up to 2.9 mg/L for serum. The highest serum creatinine values and the lowest creatinine clearances were obtained with Boehringer Mannheim Diagnostics' Jaffé method. The reciprocal of the serum creatinine and the creatinine clearance also correlated well with the glomerular filtration rate, but all methods over-estimated the glomerular filtration rates to varying degrees. Appropriate standardization of methods appears to be as important as method principle for establishing an accurate relationship between creatinine determinations and glomerular filtration rate.

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