Influence of salt on response to nitrendipine by Dahl rat kidney

1987 ◽  
Vol 252 (3) ◽  
pp. F487-F490
Author(s):  
T. H. Steele ◽  
L. Challoner-Hue

We examined the responses to the calcium channel blocker, nitrendipine, of isolated perfused kidneys from Dahl salt-sensitive (DS) and salt-resistant (DR) rats that had been stabilized on high- and low-NaCl diets. Blood pressures of high-salt DS rats exceeded those of the other three groups. After norepinephrine vasoconstriction sufficient to increase renal vascular resistance (RVR) by 50%, the superimposition of 10(-5) M nitrendipine increased the glomerular filtration rate (GFR) of high-salt DS rat kidneys by 125% over control values but returned the GFR of high-salt DR kidneys only to control. Nitrendipine superimposition increased the GFR of low-salt DS and DR rat kidneys by 124 and 40% over control values, respectively, and partially restored the RVR toward control. Nitrendipine alone, without norepinephrine, did not affect the GFR or RVR. The persistence within the DS kidney of an exaggerated glomerular circulatory “rebound” response to nitrendipine following the development of hypertension suggests the possibility of a maladaptation of DS kidney cell calcium regulation. The DR kidney manifests a similar response during salt restriction, but this disappears on a high-NaCl diet.

1998 ◽  
Vol 274 (6) ◽  
pp. R1588-R1593 ◽  
Author(s):  
Christopher S. Wilcox ◽  
Xiaolin Deng ◽  
William J. Welch

Micropuncture studies of single nephrons have shown that macula densa solute reabsorption via a furosemide-sensitive pathway activates nitric oxide (NO) generation via neuronal NO synthase (nNOS). This pathway is enhanced during salt loading. We investigated the hypothesis that changes in NO generation via nNOS in the macula densa contribute to changes in whole kidney NO generation and action during alterations in salt intake. Groups of rats ( n = 6–10) were equilibrated to high-salt (HS) or low-salt (LS) diets and were administered a vehicle (Veh), 7-nitroindazole (7-NI; a relatively selective inhibitor of nNOS), or furosemide (F; an inhibitor of macula densa solute reabsorption) with volume replacement. Compared with LS, excretion of the NO metabolites, NO2 plus NO3(NOX) was increased during HS (LS: 9.0 ± 0.5 vs. HS: 15.7 ± 0.8 μmol/24 h; P < 0.001), but this difference was prevented by 7-NI (LS: 7.4 ± 1.3 vs. HS: 9.4 ± 1.6 μmol/24 h; NS). During nonselective blockade of NOS with N G-nitro-l-arginine methyl ester (l-NAME), renal vascular resistance (RVR) increased more in HS than LS (HS: +160 ± 17 vs. LS: +83 ± 10%; P < 0.001). This difference in response to nonselective NOS inhibition was prevented by pretreatment with 7-NI (HS: +28 ± 6 vs. LS: +34 ± 8%; NS) or F with volume replacement (HS: +79 ± 11 vs. LS: +62 ± 4%; NS). In conclusion, compared with salt restriction, HS intake increases NO generation and renal action that depend on nNOS and macula densa solute reabsorption.


1987 ◽  
Vol 65 (8) ◽  
pp. 1638-1643 ◽  
Author(s):  
A. D. Baines

Current information suggests that α2-adrenoceptors do not directly influence vascular resistance or Na reabsorption in the rat kidney. To reexamine the effects of α2-agonists we used isolated rat kidneys perfused at 37.5 °C with precise measurement of renal artery pressure and flow. The recirculating perfusate contained pyruvate as the sole metabolic substrate which enabled us to use gluconeogenesis as an index of proximal tubular α1-responses. Clonidine and guanfacine in 100 nM concentrations decreased phosphate excretion without altering Na, Cl, or K reabsorption or gluconeogenesis; 500 nM concentrations increased vascular resistance and decreased glomerular filtration rate and Na, Cl, and K excretion with no significant effect on gluconeogenesis. Prior thyroparathyroidectomy prevented the antiphosphaturic but not the antinatriuretic or vascular responses. Clonidine, an α2-agonist with some α1-activity, was a more potent vasoconstrictor than methoxamine or guanfacine. In the presence of prazosin (1 μM), norepinephrine (60 nM) stimulated phosphate reabsorption; norepinephrine alone did not stimulate phosphate reabsorption which indicates α1-antagonism of this α2-response to NE. These results and a literature review suggest that increased renal α2-adrenoceptors could raise renal vascular resistance, reduce renin secretion, and antagonize parathyroid hormone effects on Pi Ca, HCO3, and Na reabsorption to produce a low renin type of hypertension with increased proximal Na reabsorption and abnormal Ca and Pi excretion.


2018 ◽  
Vol 48 (2) ◽  
pp. 87-95
Author(s):  
Tatsuyoshi Ikenoue ◽  
Kiyomi Koike ◽  
Shingo Fukuma ◽  
Satoshi Ogata ◽  
Kunitoshi Iseki ◽  
...  

Background: Although some clinical practice guidelines regarding hemodialysis recommend salt restriction, few studies have examined the association between salt intake and clinical outcomes in hemodialysis patients. This study aimed to clarify the association between salt intake and mortality in hemodialysis patients. Methods: This retrospective cohort study was based on the Japanese Society for Dialysis Therapy renal data registry database (2008) and included 88,115 adult patients who had received hemodialysis for at least 2 years. Estimated salt intake was the main predictor and was calculated from intra-dialytic weight loss and pre- and post-dialysis serum sodium levels. Nonlinear logistic regression was used to determine the association between salt intake and mortality, adjusting for potential confounders. The outcomes considered were all-cause mortality and cardiovascular death at 1 year. Results: The median (25–75th percentile) salt intake at baseline was 6.4 (4.6–8.3) g/day. At 1 year, all-cause mortality occurred in 1,845 (2.1%) patients, including 807 cardiovascular deaths. The low salt intake group (< 6 g/day) demonstrated the highest all-cause mortality and cardiovascular deaths. No association was observed between high salt intake, all-cause mortality and cardiovascular deaths. The lowest risk for all-cause mortality and cardiovascular death occurred among patients with an estimated salt intake of 9 g/day. Conclusion: Low salt intake, but not high salt intake, was associated with all-cause and cardiovascular mortality in Japanese hemodialysis patients. Further studies to justify including a lower limit of salt intake for hemodialysis patients are suggested.


1992 ◽  
Vol 262 (1) ◽  
pp. H162-H167 ◽  
Author(s):  
M. D. Johnson ◽  
B. K. Richmond

Experiments were conducted to test the hypothesis that chronic administration of an opioid receptor antagonist, naloxone, would affect the outcome of the developmental phase of hypertension in Dahl salt-sensitive (S/JR strain) rats. Accordingly, S/JR rats were maintained on either a low-salt (0.45% NaCl) or a high-salt (7% NaCl) diet for 4 wk. Half of the animals of each dietary group were treated with naloxone (100-130 micrograms/h) by osmotic minipump. Food and water intakes of the high-salt animals were measured for the first 25 days, and blood pressure was measured at the end of the 4 wk via an indwelling femoral arterial catheter. Naloxone treatment slightly but significantly reduced the level of hypertension attained in the high-salt animals (158 +/- 2 mmHg in naloxone-treated animals vs. 168 +/- 3 mmHg in control animals; P less than 0.05) and also attenuated food (and hence salt) and water intakes. Naloxone did not affect the blood pressure of the low-salt animals. To determine whether the slight attenuation of hypertension might be secondary to a reduction of salt intake, a group of control S/JR animals were fed a moderately high-salt diet (2% NaCl), and naloxone-treated S/JR animals were salt-intake matched to this group by daily adjustment of the dietary salt content. Blood pressures after 4 wk of treatment were not different between these two groups. Finally, acute administration of 1 and 30 mg/kg of naloxone failed to lower blood pressure of animals with established hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)


1984 ◽  
Vol 62 (3) ◽  
pp. 272-276 ◽  
Author(s):  
Andrew D. Baines ◽  
Rosa Drangova

We used isolated perfused rat kidneys to examine dopamine (DA) production and its relation to renal function. Both innervated and chronically surgically denervated kidneys perfused with a solution containing neither albumin nor tyrosine, excreted 0.2 ± 0.1 ng DA∙min−1∙g wet weight−1 during the 10-min collection period between 30 and 40 min after starting perfusion. When perfused with 6.7% albumin, without tyrosine, innervated kidneys excreted 1.0 ± 0.06 ng DA∙min−1∙g−1 and denervated kidneys excreted 1.0 ± 0.07 DA∙min−1∙g−1. When 0.03 mM tyrosine was included in the albumin perfusate, innervated kidneys excreted 1.2 ± 0.1 ng DA∙min−1∙g−1 (p < 0.1). Under these conditions DA excretion continued for at least 100 min at which time it was 0.6 ng∙min−1∙g−1 and 86 ng/g kidney weight had been excreted. Denervated kidneys perfused with albumin + tyrosine excreted 0.9 ± 0.13 ng DA∙min−1∙g−1. Renal stores of free DA, conjugated DA, and dihydroxyphenylalanine (DOPA) could have provided at the most 30 ng/g of DA. Carbidopa inhibited DA excretion completely. DA excretion did not correlate with renal vascular resistance, inulin clearance, or fractional sodium excretion. In summary, nonneural tissue in isolated perfused kidneys produced DA at the same rate as denervated kidneys in vivo. Less than one-third of the DA produced by isolated kidneys could have come from intrarenal stores of DOPA, free DA, and conjugated DA; the rest was synthesized from unknown precursors. Circulating DOPA and tyrosine were not the DA precursors, but albumin was required to obtain production rates similar to those in vivo. Nonneuronal DA production did not influence renal hemodynamics, glomerular filtration rate (GFR), or sodium excretion.


1995 ◽  
Vol 89 (1) ◽  
pp. 37-43 ◽  
Author(s):  
M. Sutters ◽  
R. Duncan ◽  
W. S. Peart

1. We have previously described a progressive antidiuresis in response to low-dose vasopressin infusion during salt restriction in man, despite stable or even declining plasma vasopressin concentration. In the present study we examine the hypothesis that renal sensitivity to the antidiuretic effect of arginine vasopressin may be enhanced by salt restriction. 2. Extremely low-dose infusions of arginine vasopressin were given to normal subjects after equilibration to high (260 mmol/day) and low (20 mmol/day) sodium intakes. 3. Salt restriction increased the antidiuretic effect of arginine vasopressin (2 fmol min−1 kg−1 arginine vasopressin increased urine osmolality from 67.8 ± 2.6 to 196.3 ± 35.7 mosmol/l in the high-salt study and from 268.3 ± 49 mosmol/l in the low-salt study; P < 0.05 between sodium intakes). Glomerular filtration rate, estimated from inulin clearance, was unchanged during arginine vasopressin infusion irrespective of salt intake (high salt 116.5 ± 9.4 to 118.9 ± 6.4 ml/min; low salt, 135.1 ± 9.2 to 111.2 ± 12.4 ml/min). Renal plasma flow, estimated from para-aminohippurate clearance, fell further during infusion of 2 fmol min−1 kg−1 arginine vasopressin in the low-salt study than in the high-salt study (low salt, from 555.7 ± 22.7 to 298.3 ± 27.6 ml/min; high salt, from 544.5 ± 30.2 to 452.9 ± 28.9 ml/min; P < 0.05 between sodium intakes). 4. Plasma atrial natriuretic peptide concentration increased during infusion of 2 fmol min−1 kg−1 arginine vasopressin in the low-salt study (to 136.5% ± 19.9% of baseline, P < 0.05), if anything falling in the high-salt study (to 90.5% ± 13.6% of baseline). Packed cell volume fell during arginine vasopressin infusion in the low-salt study (high salt, to 98.2% ± 0.4% of baseline; low salt, to 95.7% ± 0.4% of baseline, P < 0.05 for the low-salt study only). 5. Plasma arginine vasopressin concentration was constant throughout each study (high salt 0.48 ± 0.12 to 0.48 ± 0.1 pmol/l; low salt, 0.38 ± 0.05 to 0.4 ± 0.04 pmol/l). 6. Our findings suggest that renal sensitivity to the hydro-osmotic and vascular effects of arginine vasopressin is enhanced by salt restriction.


2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Ranna Chou ◽  
Anna Hara ◽  
DongDong Du ◽  
Namiko Shimizu ◽  
Hiroe Sakuyama ◽  
...  

We investigated the influence of maternal salt restriction during mating or gestation on birth rate and offspring growth in Dahl salt-sensitive rats (DS). DS were divided into 5 groups: DS fed a low-salt (0.3% NaCl, w/w) (DS-low) or high-salt (4% NaCl, w/w) diet (DS-high) during mating and DS-high or DS-low during gestation, and DS fed regular chow (0.75% NaCl, w/w) (DS-regular) throughout mating and gestation. During the unspecified periods, the rats were given regular chow. DS-low during mating delivered fewer infants than high-salt mothers (P<0.05). The birth rate on regular chow was 87%. Six out of 11 DS-low rats during pregnancy produced pups while the rats fed a high-salt diet all delivered pups (P<0.025). The pup survival rate was 67% for high-salt mothers during mating and 54% for mothers on a low-salt diet. The pup survival rate was 95% for mothers on a high-salt diet during pregnancy and 64% for mothers on a low-salt diet (P<0.0001). Seven out of 8 DS-regular rats during mating delivered 59 neonates. However, 66% of the neonates survived. A low-salt diet during mating or pregnancy lowers birth rate and the neonates from low-salt mothers during pregnancy were more likely to die than those from high-salt mothers.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Gangyi Zhu ◽  
Yanting Yu ◽  
Xiaoyan Wang

Candesartan is one of angiotensin II type1 receptor blockers(ARB) and commonly used as first-line antihypertensive treatment. Low salt diet is often recommended by clinicians to the patients with hypertension and kidney diseases. However,it is not clear whether salt restriction is beneficial to the patients taking ARB. In order to explore this problem, the impacts of different salt diets on blood pressure (BP),renal function and oxidative stress were determined in 2-3 months old male Sprague Dawley rats treated with candesartan. The rats were randomly divided into 4 groups fed agar-gelled food rationally with NaCl content at 0.01%, 0.8%, 2% and 4% respectively(4-7 rats/group) while all rats were intraperitoneally injected with candesartan at 1mg / kg / day for 7 days. SBP started to decline on day 2 in all except 4% NaCl groups relative to day 0 (recorded 5-6 hrs before the first injection). On day 6, systolic BP (mmHg, tail-cuff, Softron,BP-98A) was lower in 0.8% (103.7+2.3) & 0.01% (101.6+3) groups than 2% (113.5+4.1) & 4% (129.9+4.6) groups (one way ANOVA,LSD test, P<0.05) and correlated positively with food NaCl intakes (R 2 =0.9832). DBP was changed in a similar pattern as SBP. Serum creatinine (μmol/L) was higher in 0.01% group (225+39) than groups of 0.8% (1328+350), 2% (2095+242) and 4% (1576+703) while creatinine clearance (ml/day) was lower in 0.01% group (69.3+9) than groups of 0.8% (43.7+9), 2%(27.7+2) and 4%(29+0.6). In order to determine whether oxidative stress plays any role in the BP regulation and renal function maintenance, we also checked renal protein expression of ROS components. Relative to 0.8% group, renal NOXs were not altered in 0.01% group while NOX1 (145+18,% of 0.8% group), NOX2 (240+54) and NOX4 (197+41) was higher in 2% group than other groups. Mn-SOD (77+7.8), not Cu-Zn SOD, was decreased while HO1 (170+16), not HO2, was increased in 0.01% group. Renal abundance of nitrotyrosine was lower in 0.01% than other groups indicating a decreased oxidative stress, possibly caused by increase in HO1. We concluded that salt restriction with candesartan is beneficial to antihypertensive effect of AT1R blockade but disadvantage to maintenance of renal function. Thus, cautions to choice of low salt intakes are necessary when taking ARB agents.


1986 ◽  
Vol 49 (6) ◽  
pp. 423-427 ◽  
Author(s):  
K.-D. HENRY CHIN ◽  
P. E. KOEHLER

Two factors, salt concentration and incubation temperature, were examined for their effect on the formation of histamine, phenethylamine, tryptamine and tyramine during miso (soybean paste) fermentation. Misos containing 5 and 10% NaCl were prepared and incubated at 25 and 35°C. The effect of each factor was determined from the chemical and microbiological changes in the misos during fermentation. Salt level was a significant factor in the formation of amines. Higher amine levels were found in low-salt (5% NaCl) formulations than in high-salt (10% NaCl) misos. Incubation temperature within the range of 25 to 35°C during fermentation had little effect on amine formation in misos.


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