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P Morsing

Publications and source records attributed to P Morsing.

31 records · Page 2Linked to original sources
PubMed1991

Kinin and tubuloglomerular feedback in normal and hydronephrotic rats.

The role of bradykinin in resetting the tubuloglomerular feedback (TGF) mechanism was studied with the stop-flow technique in control and hydronephrotic Inactin-anesthetized rats. Glomerular function was assessed by measuring stop-flow pressure (Psf); the maximal decrease in stop-flow pressure (delta Psf) with increased loop of Henle perfusion and the perfusion that elicited half-maximal delta Psf, the turning point (TP), were determined. Bradykinin infusion resulted in resetting of TGF in both control and hydronephrotic rats but in different directions. A decreased sensitivity was found in control rats (TP increased from 18.6 to 26.4 and 16.8 to 22.1 nl/min on systemic and intratubular administration, respectively). In hydronephrotic rats the sensitivity of TGF increased. TP decreased from 19.9 to 15.2 nl/min with bradykinin administered systemically and from 18.4 to 15.0 nl/min on intratubular administration. These results show that exogenous kinin administration mimics the effects of extracellular volume expansion on TGF resetting and demonstrate a difference in resetting in hydronephrotic and control kidneys.

Animals↗
PubMed1991

Adaptation of distal convoluted tubule of rats. II. Effects of chronic thiazide infusion.

Mammalian distal tubules adapt structurally and functionally when NaCl concentration in tubule fluid is altered chronically. These experiments were designed to test the hypothesis that chronic administration of hydrochlorothiazide (HCTZ), a drug that blocks Na and Cl uptake across apical membranes of rat distal tubule cells, would reduce intrinsic transport capacity of distal tubules and reduce the number of thiazide-sensitive transporters. Osmotic pumps were implanted into rats to deliver 3.75 mg/day HCTZ or vehicle for 10-14 days. All animals were offered a solution containing 0.8% NaCl and 0.1% KCl as drinking fluid. Free-flow micropuncture after 10-14 days indicated that Na and Cl delivery to distal tubule was not significantly different in HCTZ- and vehicle-treated animals. Microperfusion in vivo with an artificial interstitial solution, with no thiazide, indicated that 10-14 days of HCTZ infusion did reduce Na transport capacity of distal tubules from 390 +/- 32 to 203 +/- 24 pmol/min (P less than 0.01). In contrast, the number of thiazide-sensitive NaCl transporters, determined as high-affinity receptors for [3H]metolazone in renal cortical membranes, was higher in HCTZ group than in controls (2.2 +/- 0.4 vs. 1.0 +/- 0.1 pmol/mg protein, P less than 0.01). These data support the hypothesis that chronic blockade of NaCl entry across apical membranes of distal tubule cells reduces NaCl transport capacity, an effect that occurs despite an increase in the number of thiazide receptors. They indicate that thiazide receptor binding studies should be interpreted in combination with direct functional measurements.

Adaptation, Physiological↗
PubMed1991

Tubuloglomerular feedback in obstructive uropathy.

The tubuloglomerular feedback (TGF) mechanism was studied in rats with chronic partial ureteral occlusion (hydronephrosis) with the use of the stop-flow pressure techniques and measurements of single nephron glomerular filtration rate. In hydropenic conditions, TGF was normal in hydronephrotic kidneys, but TGF sensitivity and activity increased in response to extracellular volume expansion, which is the opposite of normal resetting. The increased sensitivity may be due to an increased production of thromboxane A2 in the hydronephrotic kidney, since both inhibition of thromboxane synthetase and blockade of thromboxane/prostaglandin endoperoxide receptors normalized the resetting during volume expansion. Pelvic pressure in hydronephrotic kidneys was low in hydropenia and increased moderately during volume expansion. Thromboxane synthesis inhibition before volume expansion allowed pelvic pressure to increase by more than 100% as compared with untreated hydronephrotics. Also, when pelvic pressure increases were prevented during volume expansion, TGF resetting was normalized. An increased thromboxane synthesis during volume expansion may be protective in hydronephrotic kidneys, in that TGF resets to a higher sensitivity to prevent increases in glomerular filtration rate and urine formation which otherwise would increase pelvic pressure. A resetting to a higher sensitivity was also elicited by intraarterial or intratubular administration of bradykinin. This suggests that thromboxane release may be mediated through an increased bradykinin production during volume expansion in hydronephrotics. In contrast, bradykinin resets TGF to a lower sensitivity in control kidneys.

Animals↗
PubMed1990

Resetting of the pressure range for blood flow autoregulation in the rat kidney.

Both a myogenic response and the tubuloglomerular feedback control mechanism seem to be involved in autoregulation of glomerular filtration rate (GFR) and renal blood flow (RBF). Earlier experiments have shown that clamping of renal arterial perfusion pressure, below the autoregulatory range, reduces single-nephron GFR, and that this low value is maintained during the first 10-15 min after release of the clamp. It was also found that the tubuloglomerular feedback mechanism in the early declamp phase was strongly activated to reduce GFR. These findings can not be easily understood with the current knowledge of autoregulation, but would suggest a resetting of RBF and GFR autoregulation to a new level. To test this, left renal arterial perfusion pressure was reduced from 100 to 60 mmHg during 20 min with and without angiotensin converting enzyme inhibition (0.5 mg i.v. enalapril). Renal blood flow was measured with laser-Doppler flowmetry. When arterial perfusion pressure was reduced from 100 to 60 mmHg for 20 min, RBF was reduced to 77% of control and remained at this low level during the first minutes of declamp. In this situation there was an autoregulation to a new level. Renal blood flow was then slowly normalized (16.1 min). In the enalapril-treated animals RBF was only reduced to 85% during the 20 min of clamping and returned immediately to the control level at declamp. Thus, these experiments demonstrate that if renal blood flow is decreased by reducing the perfusion pressure below the normal autoregulatory range the pressure range for blood flow autoregulation resets to a lower level and that this change is mediated via the renin-angiotensin system.

Animals↗
PubMed1989

Effect of thromboxane inhibition on tubuloglomerular feedback in hydronephrotic kidneys.

The tubuloglomerular feedback (TGF) system is less sensitive after extracellular volume expansion (VE). In rats with partial ureteral obstruction, however, we have previously found increased TGF sensitivity during such expansion. Thromboxane A2 (TXA2) has been reported to be increased in the hydronephrotic kidney, and the present study was undertaken to investigate whether TXA2 might be responsible for these findings. The TGF characteristics were studied, by means of the stop-flow technique, in control and hydronephrotic rats before and after intravenous injection of either a thromboxane synthetase inhibitor or a thromboxane receptor antagonist during hydropenia. After VE, TGF was studied again. Proximal tubular stop-flow pressure (Psf) was measured during perfusion of the loop of Henle with a modified Ringer's solution, the maximal response (delta Psf) to an increased tubular flow rate was determined and the tubular perfusion rate which elicited a half-maximal decrease in Psf, designated the turning point, was recorded. In hydropenic control or hydronephrotic animals, TXA2 did not permanently change the TGF characteristics. During VE of the TXA2-blocked hydronephrotic animals, blocked both with synthetase inhibitor or receptor-antagonist, TGF was reset to a lower sensitivity like VE controls, as indicated by a high turning point and a low delta Psf. It was therefore concluded that thromboxane A2 inhibition does not influence the TGF system in hydropenia, but that the production of thromboxane A2 is responsible for the resetting of the TGF system during VE in hydronephrotic animals.

Animals↗
PubMed1988

A micropuncture assessment of the effects of contrast media of different osmolality.

The pathophysiology of radiographic contrast media-induced acute renal failure is unclear. Different causes are suggested, including hypertonicity, charged molecules, and toxicity of the media. This study deals with hemodynamic changes after injection of contrast media of high osmolarity iohexol, and metrizoate. Proximal tubular free-flow and stop-flow pressure (Psf), (the latter a marker of glomerular capillary pressure) were measured before, during, and afer injection of contrast media into the renal artery, compared with saline injection, in both normal rats and rats with ureteral obstruction (UO). Urine and electrolyte excretion also were examined. Metrizoate caused an initial decrease in Psf, from 37 to 20 mm Hg, followed by an increase to 81 mm Hg, and the value remained high for 10 minutes. During UO, the elevation of Psf was prolonged. Iohexol injection had a less marked effect. The change in glomerular capillary pressure may be dependent on the osmolarity of the contrast agent.

Animals↗
PubMed1988

Back-leak of pelvic urine to the bloodstream.

The aim of the present investigation was to measure the back-leak of pelvic urine to the blood circulation. In normopenic hydronephrotic, dehydrated hydronephrotic and dehydrated control kidneys the back-leak was estimated from a servocontrolled machine which regulated infused saline to keep a present pelvic pressure constant. The disappearance of fluid from the renal pelvis could be measured at different pressure levels, and a pressure-dependent outflow of fluid was found. From these measurements a back-leak conductance could be calculated which proved to be independent of pressure. In the lower pressure range (15-20 mmHg) there was a significantly lower conductance in the dehydrated controls compared with the dyhydrated hydronephrotic kidneys, while in the higher pressure range (25-30 mmHg) no difference was found. From electron microscopical studies the pyelorenal back-leak of fluid in both hydronephrotic and control animals seemed to be most pronounced in the fornix region, as documented by a heavy presence of horseradish peroxidase in the intracellular spaces there. Other experiments with radioactively labelled inulin, which was injected into the pelvic cavity, indicated that most of the back-leak occurred via the renal blood vessels and not through the lymphatic system. The importance of this back-leak was evident from the measurements of the total kidney glomerular filtration rate (GFR) at a slightly increased pelvic pressure, where some of the urine with radioactive tracer flows back to circulation. The back-leak of pelvic urine could also affect the concentration mechanism by removing diluted urine which had flowed over the renal papilla, and through water and urea diffusion increased papillary interstitial osmolarity.

Animals↗
PubMed1987

Tubuloglomerular feedback in animals with unilateral, partial ureteral occlusion.

Previous experiments have shown that the sensitivity of the tubuloglomerular feedback system (TGF) is reduced by volume expansion in normal rats. This reduction in sensitivity is probably mediated by changes in the renal interstitial pressure. The present study was designed to investigate the TGF control system during volume expansion in rats with chronic, partial ureteral occlusion--hydronephrosis. Hydronephrosis was induced on the left or right side according to the method described by Ulm and Miller, in weanling Sprague-Dawley rats three weeks old. Three to six weeks later the rats were prepared for whole kidney and micropuncture experiments. Sham-operated animals were used as controls. Net interstitial pressure (that is, interstitial hydrostatic pressure minus interstitial oncotic pressure) was higher in the hydronephrotic, volume expanded animals than in the volume expanded controls. From findings in earlier investigations this increase in interstitial pressure would have been expected to reduce TGF sensitivity but this sensitivity was increased in the hydronephrotic kidneys, as indicated by a reduction in the turning point, the tubular flow rate at which 50% of the maximal stop-flow pressure response was observed (14.4 nl/min, sham-operated control 33.4 nl/min). Strong activity of the TGF mechanism was also indicated by a large proximal-distal difference in the single-nephron glomerular filtration rate (11.9 nl/min versus 3.3 nl/min in sham-operated controls) in the hydronephrotic kidney during volume expansion. Thus, in hydronephrotic kidneys in the latter condition the TGF mechanism was highly sensitive and activated to reduce the glomerular filtration rate. This mechanism may protect the diseased kidney from high intrapelvic pressures which otherwise could damage the kidney during saline volume expansion.

Animals↗
PubMedDate not supplied

Pelvic pressure and tubuloglomerular feedback in hydronephrosis.

From previous studies on hydronephrotic rats in our laboratory, an increased sensitivity of the tubuloglomerular feedback (TGF) mechanism was found during extracellular volume expansion (VE). In contrast, the mechanism resets to a lower sensitivity during VE in control animals. The resetting in hydronephrotic rats was reversed by blocking the thromboxane (Tx) system. The present study was performed to measure changes in pelvic pressure (Pp) in hydronephrotic kidneys during VE, and the effect of Tx inhibition on those changes. In addition, TGF was characterized during VE of hydronephrotic rats while Pp was kept at the pre-VE level. On VE, Pp increased moderately from a control value of 2.9 mm Hg to a plateau with a mean value of 6.0 mm Hg (control, 0.7 vs. 2.1 mm Hg). After Tx inhibition, Pp was increased by more than 100%, with a plateau value of 13.6 mm Hg. When Pp was normalized and fixed, the direction of resetting of TGF was normal. The results from this study indicate that the resetting of TGF is of importance to keep glomerular filtration rate low and reduce Pp in the hydronephrotic kidney. Tx and Pp are involved in the resetting of TGF.

Animals↗
PubMedDate not supplied

Effect of prostaglandin synthesis inhibition on the tubuloglomerular feedback control in the rat kidney.

It is known that intact prostaglandin synthesis is of some importance for tubuloglomerular feedback (TGF). In this study the effects of cyclooxygenase inhibition by oral fenflumizole, an imidazole derivative, on TGF in rats after acute elevation of ureteral pressure were investigated by comparison with the TGF mechanism in untreated rats. The effects of fenflumizole on the TGF mechanism were also compared with those of indomethacin injection. To characterize the TGF mechanism proximal tubular stop-flow pressure (Psf) was measured during perfusion of the loop of Henle with an artificial perfusion solution with a composition resembling that of the proximal fluid. The perfusion rate was varied from 0 to 40 nl.min-1, in steps of 2.5-5 nl.min-1, permitting measurement of the maximal pressure response delta Psf, to increased tubular perfusion, and the perfusion rate which elicited a half-maximal drop in Psf, designated the turning point (TP). Both cyclooxygenase inhibitors caused a significant increase in TP from a control value of 21 to approximately 27 nl.min-1. TP remained at this level in fenflumizole-treated rats, even after elevation of ureteral pressure, a situation in which TGF is normally not detectable. From these and earlier investigations we conclude that the prostaglandin system is of importance for a normally operating TGF control mechanism, both under normal conditions and, especially, in conditions in which resetting of TGF is observed.

Animals↗
PubMedDate not supplied

Tubuloglomerular feedback in rats with chronic partial bilateral ureteral obstruction.

UNLABELLED: Rats with chronic partial unilateral ureteral obstruction (UUO) have a paradoxical resetting of the tubuloglomerular feedback (TGF) mechanism. During extracellular fluid volume expansion (VE) in control animals, a decrease in TGF sensitivity is normally noted. In rats with partial UUO, however, TGF sensitivity in the obstructed kidney was increased, associated with a relative reduction in single nephron glomerular filtration rate. In the present study, we examined the tubular and interstitial pressures, whole kidney function and the TGF system in rats with chronic partial bilateral ureteral obstruction. The rats were divided into preferentially ipsilaterally and preferentially contralaterally obstructed, as judged by pelvic volume. Measurements were performed both during hydropenia and during VE. During hydropenia TGF characteristics were the same in the 2 groups. During VE, however, TGF sensitivity was unchanged in the most obstructed kidneys (ipsilateral), while if the obstruction was preferentially contralateral, TGF-sensitivity decreased. This opposite change in TGF sensitivity resulted in higher electrolyte and water excretion from the least obstructed kidney. The change in TGF sensitivity was not correlated to renal interstitial pressure. IN CONCLUSION: rats with moderate chronic partial bilateral ureteral obstruction have an almost preserved function with regard to renal hemodynamics and excretion during hydropenia. During volume expansion, however, different responses were found in the least and most obstructed kidneys, with a decreased sensitivity of TGF in the least obstructed kidney, while TGF sensitivity was unchanged in the most obstructed kidney.

Animals↗