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Biomedical subjects

A E Persson

Publications and source records attributed to A E Persson.

At least 19 recordsLinked to original sources
PubMed1992

Lack of effect of intraluminal pressure on renin release from isolated afferent arterioles.

To evaluate the role of the proposed baroreceptor mechanism in the afferent arteriole in regulating renin release, we modified the isolated perfused tubule technique to perfuse afferent arterioles. Arterioles with attached glomeruli were isolated from rabbit kidneys and perfused using standard methods. To stop the arteriolar flow and allow perfusion pressure, as set by a mercury manometer, to be built up in the lumen of the vessel, the glomerulus was sucked into a constriction pipette. The preparation was continuously superfused with Krebs-Ringer solution in the first series of experiment, and a cell culture medium in the second series of experiment. The superfusate droplets were collected under mineral oil with 10-min collection intervals. The renin content of the samples was assayed by radioimmunoassay of the angiotensin I generated. In the two series of experiments we tested the effects of sequential changes in intraluminal pressure on renin release. In the first series of experiments (n = 6) the renin release was 56.3 nGU arteriole-1 min-1 in the first 10 min of sampling. The renin release was then constant for 80 min with an average of 21.6 nGU arteriole-1 min-1. In the last 30 min the renin release was 96.5 nGU arteriole-1 min-1. In the second series of experiments (n = 8) the renin release was 26.5 nGU arteriole-1 min-1 throughout the course of the experiment. These results indicate that under these conditions there is no relation between renin release and intraluminal pressure in afferent arterioles.

Animals↗
PubMed1992

Stimulation of acid secretion increases the gastric gland luminal pressure in the rat.

The gastric mucosal gland luminal pressure was measured in vivo with a pressure-sensitive microelectrode technique (servo-null) in anesthetized rats. A microelectrode was inserted into a gland lumen by means of a micromanipulator at an angle of 30 degrees to the mucosal surface. Acid secretion was estimated by measuring the pH in the solution covering the mucosa. During control conditions, when the mucosa was secreting acid spontaneously, gland luminal pressure was 12.3 +/- 1.2 mm Hg. At about 9 minutes after starting pentagastrin administration, the luminal pressure stabilized at 17.2 +/- 1.7 mm Hg. In the rats given impromidine (500 micrograms.kg-1.h-1) luminal pressure gradually increased (during 9-10 minutes) from a control level of 9.0 +/- 1.9 to 17.3 +/- 2.6 mm Hg. During the majority of experiments, the luminal pressure oscillated at 3-7 cycles per minute. The results show that intraluminal pressure increases during stimulated acid secretion, indicating that a resistance to the volume secretion exists in the upper part of the gastric crypts. This hydrostatic pressure may well be the driving force for creating channels for acid and pepsin to cross the mucus layer covering the mucosal surface.

Animals↗
PubMed1992

Captopril and time dependent changes in post- to pre-glomerular resistance ratios in remnant kidneys of pre-hypertensive rats.

Micropuncture experiments were performed on intact and remnant kidneys of male Sprague-Dawley rats before and after angiotensin converting enzyme inhibition with captopril (0.5 mg kg-1 iv). Partially nephrectomized rats were studied at 2 and 8 weeks post-surgery before the development of systemic hypertension. At 2 weeks, nephrectomized rats had a numerically higher tubular stop-flow pressure than controls (43 +/- 2 mmHg vs. 38 +/- 2 mmHg; P = 0.08) and a higher post- to pre-glomerular resistance ratio (Re/Ra) (0.40 +/- 0.03 vs. 0.31 +/- 0.03; P = 0.08). At 8 weeks, stop-flow pressure and post- to pre-glomerular resistance ratios were similar in remnant and intact kidneys. Captopril had no effect on stop-flow pressure in 2 week post-surgery nephrectomized rats or either control group, but it increased stop-flow pressure in 8 week post-surgery nephrectomized rats (40 +/- 2 to 44 +/- 2 mmHg, P = 0.04). This increase in stop-flow pressure was associated with an increase in the post- to pre-glomerular resistance ratio (0.33 +/- 0.02-0.42 +/- 0.02, P = 0.009). Stop-flow pressure was positively correlated with the post- to pre-glomerular resistance ratio in 2-week post-surgery nephrectomized rats and their respective controls when combined (r = 0.89, P = 0.0001) and 8-week post-surgery nephrectomized rats and their respective controls combined (r = 0.78, P = 0.0001). Stop-flow pressure was not significantly correlated with mean arterial pressures or welling-point pressures in these groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Renal response to volume depletion and expansion in Milan hypertensive rats.

In previous studies on Milan hypertensive (MHS) rats, we found an impaired tubuloglomerular feedback (TGF) response before, during and after development of hypertension. In the present study MHS rats and rats of the Milan normotensive strain (MNS) were investigated after 24 hours of volume depletion (VD) and subsequently after 5% isotonic volume expansion (VE) with respect to whole kidney function, interstitial hydrostatic (P(int)) and oncotic (IIint) pressures, stop-flow pressure characteristics of TGF and changes in early proximal flow rate in response to increased loop of Henle flow. MHS rats had higher mean arterial blood pressure (Pa) than MNS rats (129 vs. 101 mmHg) both after VD and after subsequent VE. No difference in glomerular filtration rate (GFR) was found. Both strains had a low urine flow rate (approximately 1.5 microliters min-1) during VD, which increased fourfold after VE. The interstitium was significantly more dehydrated in MHS, as indicated by a more negative net interstitial pressure (P(int)-IIint than in MNS (-1.3 +/- 0.3 vs. +/- 0.0 +/- 0.5 mmHg) after VE. The TGF mechanism was more activated in MHS during volume depletion, as indicated by a larger drop in stop-flow pressure (Psf) in response to loop of Henle perfusion (7.1 +/- 0.7 vs. 4.7 +/- 0.2 mmHg, P less than 0.05). However, during VD the loop of Henle flow that elicited half maximal response in Psf, the turning point (TP), was equally low in MHS and MNS (13.5 +/- 0.6 and 14.3 +/- 0.4, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Renal interstitial pressure and tubuloglomerular feedback control in rats during infusion of atrial natriuretic peptide (ANP).

Atrial natriuretic peptide (ANP), injected at physiological concentrations, is known to induce both natriuresis and diuresis. It has been suggested by some investigators that these changes result from an increasing glomerular filtration rate (GFR), but others have been unable to demonstrate an increased GFR. The tubuloglomerular feedback (TGF) mechanism is an important regulator of GFR, and the sensitivity of TGF is decreased during ANP administration. Furthermore, resetting of TGF is, in most instances, related to changes in renal interstitial hydrostatic and oncotic pressures. It is also known that ANP may increase capillary permeability which may change renal interstitial pressure. The present study was performed to examine renal interstitial pressures and the TGF mechanism during ANP infusion. In accordance with previous studies, TGF sensitivity was found to be decreased. The tubular flow rate which elicited half the maximal drop in stop-flow pressure (Psf) was increased from 18.5 to 25.7 nl min-1. In contrast, ANP infusion resulted in a decreased interstitial hydrostatic pressure and an increased interstitial oncotic pressure. From previous experiments, such changes in interstitial pressures would be expected to increase TGF sensitivity. The changes in interstitial pressure cannot, therefore, directly explain the resetting of the feedback mechanism. In conclusion, the present paper shows a decreased renal net interstitial pressure after intravenous administration of ANP.

Animals↗
PubMed1992

Captopril and tubuloglomerular feedback in remnant kidneys of prehypertensive rats.

The activity and characteristics of tubuloglomerular feedback (TGF) are altered subsequent to reductions in renal mass or blockade of the renin-angiotensin system. This study assessed the combined effects of renal ablation and captopril on TGF. Renal mass was reduced in male Sprague-Dawley rats by the surgical removal of 1 1/2 kidneys. At 2 and 8 wk postsurgery, TGF was studied by micropuncture before and after the administration of captopril (0.5 mg/kg i.v.) Before captopril, TGF in remnant kidneys (NX) was characterized by a higher tubular perfusion rate required for a 50% maximal response (TGF turning point) as compared with intact kidneys of controls (CNT) at both 2 (NX, 35 +/- 3; CNT, = 19 +/- 1 nL/min; P less than 0.05) and 8 wk (NX, 54 +/- 5; CNT, 20 +/- 1 nL/min; P less than 0.05). Captopril significantly increased the turning point in both intact and remnant kidneys at both 2 (NX, 43 +/- 2; CNT, 25 +/- 2 nL/min) and 8 wk (NX, 61 +/- 5; CNT, 28 +/- 2 nL/min) postsurgery. Captopril also significantly reduced the maximal TGF response in both intact and remnant kidneys at 2 (NX from 13 +/- 3 to 7 +/- 1 mm Hg; CNT from 10 +/- 1 to 5 +/- 1 mm Hg) and 8 wk (NX from 15 +/- 1 to 9 +/- 2 mm Hg; CNT from 13 +/- 1 to 7 +/- 1 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Long-term partial ureteral obstruction and its effects on kidney function.

Previously it has been shown that partial ureteral obstruction present in young rats for 12 weeks results in small morphological changes in the kidney as well as slightly decreased kidney function. In the present study the aim was to examine whether rats obstructed for one year had more advanced changes in morphology and kidney function. The first group of animals examined after three weeks of obstruction showed only modest changes in kidney function with a reduced potassium concentration in the urine but no reduction in the glomerular filtration rate. After one year there was a reduction in urine flow as well as in the excretion of both potassium and sodium. Urine osmolality was also reduced. Glomerular filtration rate measured in this group of animals was reduced in the obstructed kidney by about 60% compared to the contralateral one. There were only small changes in the morphology with no loss in parenchymal weight or compensatory hypertrophy, but there was a significant deformation of the papilla and an increase in inflammatory cells in the parenchyma. In conclusion hydronephrosis during a shorter period is not harmful to kidney function but if sustained for an extended time period kidney function will deteriorate.

Animals↗
PubMed1991

No persistent effect of angiotensin converting enzyme inhibitor treatment in Milan hypertensive rats despite regression of vascular structure.

Milan hypertensive rats were treated, from ages 4 to 24 weeks, with the angiotensin converting enzyme (ACE) inhibitor, perindopril, in doses of 1.5 mg/kg per day or 0.4 mg/kg per day. Controls were untreated Milan hypertensive rats. At age 24 weeks, a mesenteric biopsy was taken, from which two resistance vessels were taken out and mounted on a myograph for structural and functional analysis. Thereafter, treatment was withdrawn and the blood pressure of the rats was followed until age 36 weeks. Perindopril treatment had a dose-dependent effect on blood pressure as well as on both structural (media thickness, media: lumen ratio) and functional (estimated pressure against which vessels could contract) parameters of the resistance vessels. However, when treatment was withdrawn, blood pressure rose to (low-dose perindopril group) or above (high-dose perindopril group) control levels. The results contrast with previous studies using spontaneous hypertensive rats (SHR) where, using the same protocol, blood pressure remains low after withdrawal of treatment with ACE inhibitors, including perindopril, although the effect on resistance vessel parameters is similar. The results show that the persistent effect of ACE inhibitor therapy which has been seen in SHR is not a general feature of genetic hypertension. Furthermore, these results raise doubts as to whether the persistent effect seen in SHR is due to a general effect of ACE inhibitor treatment on vascular structure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Intracellular cytosolic free calcium concentration in the macula densa and in ascending limb cells at different luminal concentrations of sodium chloride and with added furosemide.

The juxtaglomerular apparatus fulfils several important regulatory functions in the kidney, such as tubuloglomerular feedback (TGF) control and control of renin release. The macula densa (MD) cells sense the fluid load by perceiving the distal NaCl concentration via a Na-K-2Cl cotransport system in the luminal cell membrane. It has been proposed that macula densa cell activation may involve changes in intracellular cytosolic free calcium concentration ([Ca2+]i), as one link in the chain of events activating TGF or releasing renin. We therefore investigated the changes in the intracellular calcium concentrations with fura-2, using a video system, in macula densa cells, and compared them with the changes in the corresponding concentrations in the ascending limb of the loop of Henle (c-TAL). The results show that our technique for analysing intracellular cytosolic free calcium in isolated perfused tubules is valid for this purpose, and the Kd value obtained was similar to that found by Grynkiewicz et al. (1985). The intracellular cytosolic free calcium concentration was about 90 nM both in the macula densa and c-TAL cells, and the macula densa cell intracellular cytosolic free calcium concentration increased by about 20 nM when the tubular lumen was perfused with Na and Cl at low concentrations. No significant changes were noted when furosemide was added to the perfusion solutions. We consider it hardly likely that this small change in intracellular cytosolic free calcium concentration can be entirely responsible for full activation of renin release or full inactivation of the TGF control mechanism. It would seem that the signal transmission from the macula densa cells could occur by other routes than through activation of intracellular cytosolic free calcium concentration.

Animals↗
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

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↗
PubMed1991

Mechanisms of renin release from juxtaglomerular cells.

In microdissected, nonperfused afferent arterioles changes in intravascular pressure did not affect renin secretion. On the contrary, renin release from isolated afferent arterioles perfused in a free-flow system has been reported to be sensitive to simultaneous changes in luminal pressure and flow. Hence local blood flow may be involved in the baroreceptor control of renin release. If flow is sensed, the sensor is likely to be located near the endothelial cell layer, where ion channels have been shown to be influenced by variations in shear stress.

Animals↗
PubMed1991

Macula densa cell function.

Studies concerning the sensing step in the tubuloglomerular feedback (TGF) mechanism have been conflicting. To study this step, we measured macula densa (MD) cell volume and membrane potentials in the isolated perfused ascending limb of the loop of Henle with attached glomerulus with MD segments (cTAL-MD). Addition of furosemide reduced cell volume rapidly and the effect could be reversed on removal of the drug. From the time course of cell volume changes hydraulic conductivity could be measured both in the basolateral and apical cell membrane. It was found that the apical cell membrane constituted the main barrier for water flow with a low hydraulic conductance, while the basolateral hydraulic conductance was quite high. Measurements of the basolateral electrical potential in the MD cells have shown a mean electrical potential of -56 mV. This potential was hyperpolarized by the addition of furosemide, the Cl channel blocker NPPB, or during a reduction of luminal NaCl from 150 to 30 mM, and depolarized when bath Cl concentration was reduced from 150 to 30 mM. These results are consistent with the following model for electrolytes transported and similar to the one described in the cTAL [15]. In the luminal cell membrane there is an Na-K-2Cl cotransporter that takes these ions into the MD cells and there is a potassium recycling through a K channel. On the basolateral membrane side there is an Na-K pump and a Cl channel through which chloride is transported out of the MD cell. The Na-K pump activity seems to be only 1/40 of that in the cTAL cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Chloride concentration in macula densa and cortical thick ascending limb cells.

The Cl- transport through the macula densa (MD) cells is believed to be a link in the tubuloglomerular feedback (TGF) believed to be a link in the tubuloglomerular feedback (TGF) mechanism and MD-mediated renin release. One step in this transport is probably the electroneutral and furosemide-sensitive Na(+)-K(+)-2Cl- contransport on the luminal membrane of MD cells. Another step is transport through basolateral Cl- channels. In the present study the intracellular Cl- concentration, [Cl-]i, was measured in the MD and cortical thick ascending limb (cTAL) cells, and the concentration changes elicited by blocking the Na(+)-K(+)-2Cl- cotransport with furosemide or by lowering the luminal NaCl concentration determined. We also investigated the effects of blocking the basolateral Cl- channels. A preparation consisting of a segment of the cTAL, MD cells, and the attached glomerulus was dissected from rabbit kidneys. The preparation was loaded with the Cl(-)-sensitive fluorophore SPQ, and perfused by using the isolated and perfused tubule technique. The intracellular chloride concentration was determined with a video system using digital imaging that measured the intensity of the emitted SPQ fluorescence. The T 1/2 of the leakage of SPQ was found to be (197 +/- 60) min (n = 9). With 150 mM NaCl in the lumen and bath, [Cl-]i in MD cells was 47 +/- 13 mM (n = 8) and 54 +/- 13 mM (n = 5) in cTAL cells. When furosemide (10(-4) M) was added to the luminal perfusion, the MD cell [Cl-]i was reduced to 6 +/- 2 mM. The corresponding value in cTAL cells was 5 +/- 3 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Optical studies on the action of furosemide on macula densa and cortical thick ascending limb cells. Intracellular calcium fluorescence measurements.

The present study shows the successful use of an optical technique that describes the application of both differential interference contrast (DIC) and fluorescence microscopy to the study of structure-function relationships in isolated perfused cTAL-MD segments of the nephron. Image-intensified video microscopy and digital image processing techniques were used to simultaneously and directly visualize and quantify [Ca+2]i in individual cTAL cells and MD cells. This study also indicates that no large changes in MD [Ca+2]i can be observed under maneuvers that are known to affect the autoregulatory mechanisms of single nephron glomerular filtration rate. Therefore, it is less likely that MD [Ca+2]i could be a link in the transmission of the signal from the MD cells to the rest of the cells in the juxtaglomerular apparatus for the release of the TGF mechanism and/or renin. Possibly some other mechanism like the electrolyte transport itself, that can alter the solute concentration and tonicity of the Goormaghtigh cell field (juxtaglomerular interstitium), may be the signal to proceed with the rest of the events developed by the juxtaglomerular apparatus to control single nephron glomerular filtration rate.

Animals↗