Direct effects of endothelin in the rat kidney

1990 ◽  
Vol 258 (2) ◽  
pp. F397-F402 ◽  
Author(s):  
T. Katoh ◽  
H. Chang ◽  
S. Uchida ◽  
T. Okuda ◽  
K. Kurokawa
Keyword(s):  
Renal Artery ◽  
Rat Kidney ◽  
Renal Plasma Flow ◽  
Urine Volume ◽  
Fractional Excretion ◽  
Left Renal Artery ◽  
Dependent Manner ◽  
Direct Effects ◽  
Dose Dependent

In the present study, we tested the direct effects of endothelin (ET) on rat kidney in vivo. ET was infused into the left renal artery of anesthetized rats at a rate of 0.5, 5, 20, or 40 pmol/h. ET reduced ipsilateral urine volume (V), clearance of inulin (CIN), and clearance of p-aminohippuric acid (CPAH) in a dose-dependent manner. Thus ET at 20 pmol/h did not change V but decreased renal plasma flow (RPF) and glomerular filtration rate (GFR) by 27.6 +/- 14.3 and 30.8 +/- 10.4%, respectively, in the ipsilateral kidney. ET at 0.5 pmol/h was without effect and at 5 pmol/h had only minor effects on CIN and CPAH of ipsilateral kidney. At 40 pmol/h, ET reduced ipsilateral V, GFR, and RPF by 52.3 +/- 21.4, 58.4 +/- 14.5, and 72.5 +/- 10.6%, respectively. Filtration fraction and fractional excretion of Na remained unchanged during ET infusion. ET, 40 pmol/h, infused into the renal artery together with atrial natriuretic peptide (ANP) at a rate of 12 pmol/h reduced the ipsilateral V, GFR, and RPF by 33.2 +/- 6.3, 26.1 +/- 6.0, and 27.2 +/- 7.1%, respectively, decrements less than those with ET alone. When a calcium-channel blocker nicardipine was infused at a rate of 2.5 micrograms/h into the renal artery together with ET, 20 pmol/h, there was little change in the ipsilateral V, RPF, and GFR; ET, 40 pmol/h, with nicardipine did not change V and decreased GFR and RPF by 25.9 +/- 5.6 and 23.1 +/- 10.8%, respectively, decrements less than those without nicardipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Permissive role of dopamine in renal action of ANP in volume-expanded rats

1989 ◽  
Vol 257 (2) ◽  
pp. F300-F309 ◽  
Author(s):  
T. Katoh ◽  
S. Sophasan ◽  
K. Kurokawa
Keyword(s):  
Renal Plasma Flow ◽  
Sch 23390 ◽  
Urine Volume ◽  
Fractional Excretion ◽  
Systemic Circulation ◽  
Left Renal Artery ◽  
Renal Effects ◽  
Renal Action ◽  
Permissive Role

A possible role of dopamine in the diuretic and natriuretic action of atrial natriuretic peptide (ANP) was evaluated in the rat. ANP was infused into the left renal artery of anesthetized rats whose kidneys were denervated. ANP both at 12 and 1.2 pmol/h caused immediate ipsilateral increases in urine volume (V), urine Na excretion (UNaV), and fractional excretion of Na (FENa). Ipsilateral glomerular filtration rate (GFR) and renal plasma flow (RPF) increased with 12 pmol/h ANP but not with 1.2 pmol/h ANP. Intravenous infusion of haloperidol, Sch-23390, or carbidopa markedly attenuated the increase in V, UNaV, and FENa with 12 pmol/h ANP and completely abolished the increases in GFR and RPF. Haloperidol, Sch-23390, and carbidopa also completely abolished the renal effects of 1.2 pmol/h ANP. In the presence of carbidopa, a small dose of dopamine infused into the systemic circulation, which by itself has no effects on blood pressure, V, GFR, RPF, and UNaV, restored the diuretic and natriuretic effects of ANP. In addition, an increase in urinary guanosine 3',5'-cyclic monophosphate by ANP was not affected by either haloperidol or carbidopa. These data indicate that dopamine may be necessary, as a permissive agent, for the renal effects of ANP to manifest and that the effects of dopamine may be independent of ANP-stimulated guanylate cyclase activation.

Effect of acetylcholine, atropine, and physostigmine on renal function in the dog

1964 ◽  
Vol 206 (3) ◽  
pp. 492-498 ◽  
Author(s):  
Arthur J. Vander
Keyword(s):  
Renal Artery ◽  
Renal Plasma Flow ◽  
Left Kidney ◽  
Urine Volume ◽  
Indirect Evidence ◽  
Urine Osmolality ◽  
Sodium Concentration ◽  
Sodium Reabsorption ◽  
Left Renal Artery ◽  
Parasympathetic Innervation

Acetylcholine (1–500 µg/min), atropine (.002–.12 mg/kg min), or physostigmine (.01–.08 mg/min) was infused directly into the left renal artery of anesthetized dogs, and right and left kidney functions were compared. Acetylcholine produced variable changes in glomerular filtration rate (–30 to +55%), but always increased renal plasma flow (4–115%), sodium excretion (20–365 µm/min), potassium excretion (1–56 µm/min), and urine volume (.25–3.1 ml/min). Filtration fraction, urine osmolality, and medullary sodium concentration were always reduced. These changes could all be reversed or prevented by atropine. Stop-flow studies failed to demonstrate any distal tubular inhibition of sodium reabsorption by acetylcholine. Neither atropine nor physostigmine, when infused into the renal artery by itself, produced any changes in renal hemodynamics or electrolyte excretion. These data demonstrate that acetylcholine can decrease renal arteriolar resistance and inhibit tubular sodium reabsorption. They also provide indirect evidence which supports, but does not prove, the hypothesis that the kidney lacks parasympathetic innervation.

Cyclosporin and quinidine inhibition of renal digoxin excretion: evidence for luminal secretion of digoxin

1992 ◽  
Vol 263 (4) ◽  
pp. F613-F622 ◽  
Author(s):  
I. A. De Lannoy ◽  
G. Koren ◽  
J. Klein ◽  
J. Charuk ◽  
M. Silverman
Keyword(s):  
Renal Artery ◽  
Renal Vein ◽  
Left Renal Vein ◽  
Basolateral Membrane ◽  
Resistant Cell Line ◽  
Dilution Method ◽  
Left Renal Artery ◽  
Recovery Ratio ◽  
Dependent Manner

We studied the in vivo luminal and contraluminal uptake of [3H]digoxin in dog kidney using the single-pass multiple indicator dilution method. A bolus tracer of 125I-albumin (plasma reference), creatinine, or L-[14C]glucose [extracellular reference (ecf)] and [3H]digoxin (or [3H]ouabain) was injected into the left renal artery, and timed serial samples were collected from the left renal vein (basolateral uptake) and left and right ureters (luminal uptake). [3H]ouabain was excreted solely by filtration and exhibited saturable and irreversible binding at the basolateral surface. Uptake of [3H]digoxin across the basolateral membrane was large and nonsaturable. Despite urine flow-dependent reabsorption and approximately 20% protein binding, the urine recovery ratio for [3H]-digoxin/glomerular (ecf) marker was 0.97 +/- 0.04 (n = 29), indicating net digoxin secretion. After intravenous infusions of cyclosporin in Cremophor EL (0.5-3.5 microM), the urine recovery ratio decreased in a dose-dependent manner from control values of 1.13 +/- 0.06 (n = 12) to 0.62 +/- 0.03 (n = 14). There was no change in the relative renal vein recovery. Left renal artery infusion of quinidine (37.5 micrograms.min-1.kg-1) decreased the relative urine recovery of [3H]digoxin by 46% (n = 6) but had no effect on postglomerular extraction. Cyclosporin and quinidine are known inhibitors of P-glycoprotein. But digoxin did not compete with [3H]azidopine for binding in rat brush-border membranes or membranes prepared from the multidrug-resistant cell line CHRC5. The exact mechanism for renal digoxin secretion remains to be determined, but our results point to a luminal localization of this secretory system.

Effects of NO-Donors on Thrombus Formation and Microcirculation in Cerebral Vessels of the Rat

1996 ◽  
Vol 76 (01) ◽  
pp. 111-117 ◽  
Author(s):  
Yasuto Sasaki ◽  
Junji Seki ◽  
John C Giddings ◽  
Junichiro Yamamoto
Keyword(s):  
Blood Flow ◽  
Thrombus Formation ◽  
Dependent Manner ◽  
Red Cell ◽  
Cell Velocity ◽  
Red Cell Velocity ◽  
The Mean ◽  
Wall Shear ◽  
Dose Dependent

SummarySodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), are known to liberate nitric oxide (NO). In this study the effects of SNP and SIN-1 on thrombus formation in rat cerebral arterioles and venules in vivo were assessed using a helium-neon (He-Ne) laser. SNP infused at doses from 10 Μg/kg/h significantly inhibited thrombus formation in a dose dependent manner. This inhibition of thrombus formation was suppressed by methylene blue. SIN-1 at a dose of 100 Μg/kg/h also demonstrated a significant antithrombotic effect. Moreover, treatment with SNP increased vessel diameter in a dose dependent manner and enhanced the mean red cell velocity measured with a fiber-optic laser-Doppler anemometer microscope (FLDAM). Blood flow, calculated from the mean red cell velocity and vessel diameters was increased significantly during infusion. In contrast, mean wall shear rates in the arterioles and venules were not changed by SNP infusion. The results indicated that SNP and SIN-1 possessed potent antithrombotic activities, whilst SNP increased cerebral blood flow without changing wall shear rate. The findings suggest that the NO released by SNP and SIN-1 may be beneficial for the treatment and protection of cerebral infarction

scholarly journals Anti-tumor activity of a novel proteasome inhibitor D395 against multiple myeloma and its lower cardiotoxicity compared with carfilzomib

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Xuxing Shen ◽  
Chao Wu ◽  
Meng Lei ◽  
Qing Yan ◽  
Haoyang Zhang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Proteasome Inhibitor ◽  
Osteoclast Differentiation ◽  
Dependent Manner ◽  
Serum Enzyme ◽  
Herg Channels ◽  
Anti Tumor Activity ◽  
Dose Dependent

AbstractCarfilzomib, a second-generation proteasome inhibitor, has significantly improved the survival rate of multiple myeloma (MM) patients, but its clinical application is still restricted by drug resistance and cardiotoxicity. Here, we identified a novel proteasome inhibitor, D395, and assessed its efficacy in treating MM as well as its cardiotoxicity at the preclinical level. The activities of purified and intracellular proteasomes were measured to determine the effect of D395 on the proteasome. CCK-8 and flow cytometry experiments were designed to evaluate the effects of D395 on cell growth and apoptosis. The effects of D395 and carfilzomib on serum enzyme activity, echocardiography features, cardiomyocyte morphology, and hERG channels were also compared. In our study, D395 was highly cytotoxic to MM cell lines and primary MM cells but not normal cells, and it was well tolerated in vivo. Similar to carfilzomib, D395 inhibited osteoclast differentiation in a dose-dependent manner. In particular, D395 exhibited lower cardiotoxicity than carfilzomib in all experiments. In conclusion, D395 is a novel irreversible proteasome inhibitor that has remarkable anti-MM activity and mild cardiotoxicity in vitro and in vivo.

scholarly journals Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 386
Author(s):  
Tung-Hu Tsai ◽  
Yu-Jen Chen ◽  
Li-Ying Wang ◽  
Chen-Hsi Hsieh
Keyword(s):  
Stereotactic Body Radiation Therapy ◽  
In Vivo Studies ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Hep G2 ◽  
Time Curve ◽  
Dose Dependent

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).

Papaya shoot tip associated endophytic bacteria isolated from in vitro cultures and host–endophyte interaction in vitro and in vivo

2007 ◽  
Vol 53 (3) ◽  
pp. 380-390 ◽  
Author(s):  
Pious Thomas ◽  
Sima Kumari ◽  
Ganiga K. Swarna ◽  
T.K.S. Gowda
Keyword(s):  
Culture Medium ◽  
Carica Papaya ◽  
In Vitro Cultures ◽  
Dependent Manner ◽  
16S Rdna Sequence ◽  
16S Rdna Sequence Analysis ◽  
Single Organism ◽  
Dose Dependent

Fourteen distinct bacterial clones were isolated from surface-sterilized shoot tips (~1 cm) of papaya (Carica papaya L. ‘Surya’) planted on Murashige and Skoog (MS)-based papaya culture medium (23/50 nos.) during the 2–4 week period following in vitro culturing. These isolates were ascribed to six Gram-negative genera, namely Pantoea ( P. ananatis ), Enterobacter ( E. cloacae ), Brevundimonas ( B. aurantiaca ), Sphingomonas , Methylobacterium ( M. rhodesianum ), and Agrobacterium ( A. tumefaciens ) or two Gram-positive genera, Microbacterium ( M. esteraromaticum ) and Bacillus ( B. benzoevorans ) based on 16S rDNA sequence analysis. Pantoea ananatis was the most frequently isolated organism (70% of the cultures) followed by B. benzoevorans (13%), while others were isolated from single stocks. Bacteria-harboring in vitro cultures often showed a single organism. Pantoea, Enterobacter, and Agrobacterium spp. grew actively on MS-based normal papaya medium, while Microbacterium, Brevundimonas, Bacillus, Sphingomonas, and Methylobacterium spp. failed to grow in the absence of host tissue. Supplying MS medium with tissue extract enhanced the growth of all the organisms in a dose-dependent manner, indicating reliance of the endophyte on its host. Inoculation of papaya seeds with the endophytes (20 h at OD550 = 0.5) led to delayed germination or slow seedling growth initially. However, the inhibition was overcome by 3 months and the seedlings inoculated with Pantoea, Microbacterium, or Sphingomonas spp. displayed significantly better root and shoot growths.

Triphenyltin chloride induces spindle microtubule depolymerisation and inhibits meiotic maturation in mouse oocytes

2014 ◽  
Vol 26 (8) ◽  
pp. 1084 ◽  
Author(s):  
Yu-Ting Shen ◽  
Yue-Qiang Song ◽  
Xiao-Qin He ◽  
Fei Zhang ◽  
Xin Huang ◽  
...  
Keyword(s):  
Polar Body ◽  
Meiotic Maturation ◽  
Dependent Manner ◽  
Germinal Vesicle Breakdown ◽  
Mouse Oocytes ◽  
First Polar Body ◽  
Triphenyltin Chloride ◽  
Dose Dependent

Meiosis produces haploid gametes for sexual reproduction. Triphenyltin chloride (TPTCL) is a highly bioaccumulated and toxic environmental oestrogen; however, its effect on oocyte meiosis remains unknown. We examined the effect of TPTCL on mouse oocyte meiotic maturation in vitro and in vivo. In vitro, TPTCL inhibited germinal vesicle breakdown (GVBD) and first polar body extrusion (PBE) in a dose-dependent manner. The spindle microtubules completely disassembled and the chromosomes condensed after oocytes were exposed to 5 or 10 μg mL–1 TPTCL. γ-Tubulin protein was abnormally localised near chromosomes rather than on the spindle poles. In vivo, mice received TPTCL by oral gavage for 10 days. The general condition of the mice deteriorated and the ovary coefficient was reduced (P < 0.05). The number of secondary and mature ovarian follicles was significantly reduced by 10 mg kg–1 TPTCL (P < 0.05). GVBD decreased in a non-significant, dose-dependent manner (P > 0.05). PBE was inhibited with 10 mg kg–1 TPTCL (P < 0.05). The spindles of in vitro and in vivo metaphase II oocytes were disassembled with 10 mg kg–1 TPTCL. These results suggest that TPTCL seriously affects meiotic maturation by disturbing cell-cycle progression, disturbing the microtubule cytoskeleton and inhibiting follicle development in mouse oocytes.

scholarly journals The Antiinfective Effects of Velvet Antler of Formosan Sambar Deer (Cervus unicolor swinhoei) onStaphylococcus aureus-Infected Mice

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Ting-Yeu Dai ◽  
Chih-Hua Wang ◽  
Kun-Nan Chen ◽  
I-Nung Huang ◽  
Wei-Sheng Hong ◽  
...  
Keyword(s):  
Lipoteichoic Acid ◽  
Lavage Fluid ◽  
Dependent Manner ◽  
Protective Mechanisms ◽  
Velvet Antler ◽  
Sambar Deer ◽  
Dose Dependent ◽  
Cervus Unicolor

We assayed the effects of velvet antler (VA) of Formosan sambar deer (Cervus unicolor swinhoei) and its extracts on the anti-infective activity against pathogenicStaphylococcus aureus in vitroandin vivoin this study.In vitrodata indicated that the VA extracts stimulated the proliferation of resting splenocytes and macrophages in a dose-dependent manner up to the highest concentration used (150 μg mL−1). The production of proinflammatory cytokines (TNF-α, IL-6, IL-12) by lipoteichoic acid was significantly suppressed after being cocultured with the VA extracts in a dose-dependent manner. Animal test inS. aureus-infected mice demonstrated that the numbers of bacteria determined in the kidneys and peritoneal lavage fluid ofS. aureus-infected mice were significantly higher than those found in the same organs of mice pretreated with the VA samples. Moreover, the highly enhanced phagocytic activity of macrophages was further verified afterin vitrotreatment with the VA samples. The protective mechanisms of the VA samples might include an immune enhancer and an inflammatory cytokine suppressor.

Immunomodulatory activities of whey fractions in efferent prefemoral lymph of sheep

1996 ◽  
Vol 63 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Chun W. Wong ◽  
Geoffrey O. Regester ◽  
Geoffrey L. Francis ◽  
Dennis L. Watson
Keyword(s):  
Immune Responses ◽  
Bovine Milk ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Milk Whey ◽  
Significant Difference ◽  
Lymphocyte Phenotypes ◽  
Dose Dependent

SummaryStudies on the immunomodulatory activities of ruminant milk and colostral whey fractions were undertaken. By comparing with boiled colostral whey in a preliminary experiment, a putative heat-labile immunostimulatory factor for antibody responses was found to be present in ovine colostral whey. Studies were then undertaken in sheep in which the efferent prefemoral lymphatic ducts were cannulated bilaterally, and immune responses in the node were measured following subcutaneous injection in the flank fold of whey protein preparations of various purities. A significant sustained decline of efferent lymphocyte output was observed following injection with autologous crude milk whey or colostral whey preparations, but no changes were observed in interferon-gamma levels in lymph plasma. Two bovine milk whey fractions (lactoperoxidase and lactoferrin) of high purity were compared in bilaterally cannulated sheep. A transient decline over the first 6 h was seen in the efferent lymphocyte output and lymph flow rate after injection of both fractions. A significant difference was seen between the two fractions in interferongamma levels in lymph at 6 h after injection. However, no significant changes in the proportion of the various efferent lymphocyte phenotypes were seen following either treatment. Whereas both fractions showed a significant inhibitory effect in a dose-dependent manner on the proliferative response of T lymphocytes, but not B lymphocytes, to mitogenic stimulation in vitro, no similar changes were seen following in vivo stimulation with these two fractions.

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