Dynamics of tubuloglomerular feedback adaptation to acute and chronic changes in body fluid volume.
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Biomedical subjects
Publications and source records attributed to L C Moore.
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An isomorphic, dynamic model of the antidiuretic medulla and distal tubule was used to determine how vasa recta (VR) plasma flow and the nature of descending limb (DLH) equilibration influences inner medullary urine concentrating ability in the steady state. Four DLH modes were examined: water recycling with limited solute permeability, ideal water recycling, mixed water-solute recycling, and strict solute recycling. Each DLH mode was evaluated with and without thin ascending limb (tALH) NaCl active transport. Results indicate that VR plasma flow strongly affects medullary solute accumulation, that NaCl reabsorption from passive tALH is insufficient to establish a positive corticomedullary NaCl gradient, that even limited DLH solute entry compromises the medulla's ability to establish an axial osmotic gradient without active transport, and that with tALH active NaCl transport, positive inner medullary NaCl and osmotic gradients could be established with all four DLH modes. We conclude that tALH NaCl active transport or some other form of osmotic work must be invoked to account quantitatively for inner medullary concentrating effects in rodents.
A mathematical model of the renal medulla predicted patterns of NaCl and urea concentration and flow rate when a rat undergoing water diuresis receives antidiuretic hormone (ADH), We tested these predictions with micropuncture and clearance experiments in Brattleboro rats lacking endogenous ADH. The model successfully predicted urine flow rate, urea excretion rate, and ascending vasa recta (AVR) solute concentration patterns. A novel result the model correctly foresaw was that AVR urea concentration lagged behind NaCl, because ADH temporarily interrupted urea recycling. The model suggested that this lag would be carried over to descending limb of Henle's loop (DLH) fluid only if DLH permeabilities allowed solutes as well as water to move across the DLH wall, but not if solute movement was negligible. Experimental results showed the lag, therby suggesting significant solute entry into DLH fluid during the transition, and, by extension, in other conditions as well, As shown in a companion paper (Am. J. Physiol. 239 (Renal Fluid Electrolyte Physiol. 8): F57-F71, 1980), solute permeation across DLH limits hypertonic urine formation in the inner medulla unless thin ascending limbs perform active transport of NaCl.
Tubuloglomerular feedback (TGF) mediation of autoregulation was investigated by measuring the response of single nephron glomerular filtration rate (SNGFR) to changes in arterial pressure (AP) following acute or chronic TGF inhibition. In hydropenic rats with intact TGF, distal SNGFR was 25.0 +/- 1.2 (SE) and 23.9 +/- 1.4 nl/min at AP of 111 and 135 mmHg, respectively. In the same 20 nephrons during proximal tubular microinfusion of furosemide, distal SNGFR was 23.6 +/- 1.4 (n = 16) and 29.7 +/- 1.4 nl/min (n = 20) (P less than 0.001, n = 16) at 112 and 133 mmHg. When determined proximally, SNGFR was 25.6 +/- 1.0 and 29.5 +/- 0.9 nl/min (P less than 0.001, n = 31) at 112 and 157 mmHg; kidney GFR increased similarly. These data and the predictions of a GFR model were then used to estimate autoregulatory efficiency. This analysis indicated that partial autoregulation occurred during TGF inhibition. Therefore, TGF is an essential, but probably not the only, mechanism mediating SNGFR autoregulation.
The permeability of the amphibian oocyte nuclear envelope in situ has been determined for three tritiated dextrans. The envelope is a sieve, restricting molecular movement between the cytoplasm and nucleus. The patent radius of its pores is about 45å.
[(3)H]Inulin (mol wt approximately 5,500) solutions are microinjected into the cytoplasm of mature oocytes of Rana pipiens and the subsequent movement of the solute recorded by quantitative ultralow temperature autoradiography. The autoradiographs show transient cellular diffusion gradients, the influence of the nucleus on these gradients, and the nuclear:cytoplasmic distribution of inulin. Analysis leads to the following conclusions: (a) Inulin diffuses in cytoplasm at about 3 x 10(-6) cm(2)/s, or one-fifth as rapidly as in water. Most of this decrease is attributable to the increased tortuosity of the diffusional path due to the presence of inclusions and macromolecules. (b) The nuclear envelope is very permeable to inulin; its resistance to inulin's passage is similar to that of cytoplasm. The envelope appears to play a negligible role in regulating the nucleocytoplasmic movement of solutes smaller than macromolecules, (c) Inulin concentrates in the nucleus to four times its cytoplasmic level; this is attributed to solute exclusion from cytoplasmic water. Evidence is presented that among hydrophilic solutes the degree of exclusion increases with molecular size. The potential significance of cytoplasmic exclusion processes to understanding secretion and the intracellular movement of macromolecules is briefly discussed.
Two days after coronary artery bypass, a 75-year-old woman had sudden dense left-sided hemiplegia. A transthoracic echocardiogram showed a suspicious mass in the right atrium and right ventricle, which was confirmed by transesophageal echocardiography. Transesophageal echocardiography further demonstrated an elongated mass across a patent foramen ovale. Deep femoral venous thrombosis and massive cerebral infarction were also noted by Doppler ultrasonography and head computed tomographic scanning, respectively. Paradoxical embolization was thought to be the cause of the stroke.
The mechanisms responsible for the impairment of renal blood flow (RBF) autoregulation in cyclosporine nephrotoxicity were investigated with clearance and micropuncture studies in anesthetized rats. Early chronic cyclosporine nephrotoxicity (CCN) was induced in male rats by daily intramuscular injection of 10 mg/kg/day cyclosporine-A in olive oil for 7 days; control (CON) rats received vehicle injections. Glomerular filtration rate and RBF were both reduced by 33% in CCN when compared to CON rats. RBF autoregulation was also significantly impaired in CCN, with an autoregulation index (AI) of 0.53 +/- 0.03 vs. 0.16 +/- 0.01 in CON rats. Micropuncture studies showed that the tubuloglomerular feedback (TGF) system is not impaired in CCN. Rather, in CCN there was a slight resetting such that the maximum TGF response was greater and the onset occurred at lower rates of perfusion than in CON. In contrast, further micropuncture studies demonstrated that TGF-independent autoregulation of glomerular capillary pressure was significantly impaired in CCN, with an AI of 0.86 +/- 0.09 vs. 0.57 +/- 0.06 in CON. These results indicate that the loss of autoregulatory ability in rats with CCN results from substantial impairment of the myogenic autoregulatory mechanism that is an intrinsic property of the preglomerular vasculature of the kidney.
Alternative splicing of CREB (cAMP response element binding protein) and CREM (cAMP response element modulator) mRNAs in separated pachytene spermatocyte, round spermatid, and elongated spermatid fractions and the germ cell-derived immortalized cell line GC-2spd(ts) was studied by reverse transcription polymerase chain reaction (RT-PCR). Both primary germ cells and the GC-2spd(ts) cell line expressed the testis-specific CREB splice variant containing exon W. In the CREB C-E exon region, both primary germ cells and GC-2spd(ts) cells produced RT-PCR products that included exon Y. RT-PCR using CREM primers produced multiple bands in primary germ cells. The truncated CREAM deltaC-G form was found in all the germ cell fractions. The smaller splice forms of CREM were more prominent in the GC-2spd(ts) cells. GC-2spd(ts) cells resembled F9 teratocarcinoma cells more closely than primary germ cells with respect to the relative expression of both CREB and CREM alternative splice products. In Sertoli cells, RT-PCR products of CREB exon lacking W and the product corresponding to CREM delta C-G were most prominent. These data show that the GC-2spd(ts) cell line retains some qualitative characteristics of primary germ cells with respect to alternative splicing of CREB and CREM mRNA.