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A E Persson

Publications and source records attributed to A E Persson.

At least 37 records · Page 2Linked to original sources
PubMed1997

Angiotensin II induces a tachyphylactic calcium response in the rabbit afferent arteriole.

The influence of repeated administration of angiotensin II (AII) on smooth muscle calcium concentration ([Ca2+]i) was studied in isolated rabbit renal afferent arterioles loaded with the calcium-sensitive fluorescent probe Fura-2. [Ca2+]i was evaluated in the proximal and distal parts of the afferent arterioles. AII (10(-8) M) increased the [Ca2+]i in both these regions. A second administration of AII, however, did not elicit any response in [Ca2+]i. The response to noradrenaline administration at the end of the experiment was not affected, i.e. there was no fading or cross-desensitization. Since this desensitization was specific for AII, it was of the tachyphylaxis type. Increasing doses of AII (10(-11)-10(-8) M) did not reverse the tachyphylaxis. However, in the proximal part, pretreatment with the voltage-sensitive calcium channel blocker nifedipine (10(-6) M) blunted the tachyphylactic effect of a second administration of AII. When L-arginine (L-Arg) was administered to the bath solution, thus activating the NO system, the development of tachyphylaxis was suppressed in the proximal region. Pretreatment with the protein kinase C (PKC) inhibitor chelerythrine (10(-6) M) did not affect the tachyphylaxis. We conclude that the calcium response to AII in the isolated rabbit afferent arteriole shows tachyphylaxis. This tachyphylaxis cannot be reversed by applying increasing doses of AII (10(-11)-10(-8) M). PKC does not seem to be involved in the tachyphylactic phenomenon in this preparation. It was also found that nifedipine and NO reduced the tachyphylaxis.

Alkaloids↗
PubMed1997

Effects of stimulation and inhibition of protein kinase C on the cytosolic calcium concentration in rabbit afferent arterioles.

The effect of the protein kinase C (PKC) inhibitor chelerytrine (Ch) and the PKC activator 12-0-tetradecanoyl-phorbol-13-acetate (TPA) on the cytosolic calcium concentration ([Ca2+]i) in isolated intact rabbit afferent arterioles was investigated. [Ca2+]i was measured in the proximal and distal parts of the arteriole. Administration of 1 microM Ch gave rise to a peak followed by an elevated level of [Ca2+]i in both these parts. Neither the peak nor the elevated level of [Ca2+]i was significantly reduced by 1 microM nifedipine. The relative peak increase in [Ca2+]i in response to 1 microM noradrenaline (NA) or to 10 nM angiotensin II (AII) was significantly blunted in both parts after preincubation with 1 microM Ch. Depolarization with 25 mM K+ increased [Ca2+]i in both parts. Preincubation with Ch did not affect the increase in [Ca2+]i induced by 25 mM K+. TPA (10 and 100 nM) did not significantly affect the basal [Ca2+]i in the afferent arteriole. The [Ca2+]i response to NA or 25 mM K+ was not affected by TPA. We conclude that blockade of PKC increases [Ca2+]i in afferent arteriolar smooth muscle by a mechanism independent of L-type voltage-sensitive calcium channels. Inhibition of PKC blunts the relative increase in [Ca2+]i in response to AII and, to a lesser extent, that induced by NA. We conclude that PKC might be important in modulating the calcium changes that occur in response to these vasoconstrictors.

Adrenergic alpha-Agonists↗
PubMed1996

Effects of acute and chronic unilateral renal denervation on the tubuloglomerular feedback mechanism.

We recently observed a time-dependent resetting of the tubuloglomerular feedback (TGF) sensitivity to a subnormal level after acute unilateral renal denervation (aDNX). The present investigation compares the effects of aDNX with those of chronic unilateral renal denervation (cDNX), i.e one week after aDNX. All experiments were performed in anaesthetized rats prepared for micropuncture. cDNX led to increases in urine, sodium and potassium excretion in denervated kidneys, while contralateral kidneys showed reduced excretion of these parameters. GFR was increased in denervated kidneys, but unchanged on the contralateral side. TGF activity was determined by measuring the maximal stop-flow pressure response (delta Psf) and the tubular flow rate at which 50% of the maximal response occurred (turning point; TP). cDNX decreased TGF sensitivity, as indicated by an increased TP from 19.1 nL/min in sham-DNX to 26.1 nL/min. Concomitantly, TP in contralateral kidneys was significantly decreased to 15.9 nL/min, aDNX led to a greater sensitivity reduction: TP increased from 19.8 to 34.0 nL/min and contralaterally TP decreased to 14.0 nL/min. delta Psf in cDNX increased by 63% compared to sham-DNX, while on the contralateral side this was unchanged. No difference in delta Psf was found between control, DNX and contralateral kidneys in the aDNX group. In summary, these experiments show that the previously reported decrease in TGF sensitivity in aDNX kidneys still persists after one week, although less pronounced. As a result of the decreased TGF sensitivity, GFR is kept on a high level in cDNX kidneys. Contralateral kidneys show reversed resetting.

Animals↗
PubMed1996

Inhibitory effects on the DNA binding of AP-1 transcription factor to an AP-1 binding site modified by benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide diastereomers.

Benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide is an established carcinogen, known to covalently bind to DNA, in particular to the exocyclic aminogroup of dG, and thereby cause conformational changes to the double helix. AP-1 is a well-studied transcription factor that specifically binds to the DNA sequence 5'-d(TGAGTCA). The effects of more or less randomly distributed BPDE adducts on DNA have been studied in different contexts, as well as the effects of different stimuli on transcription factor binding affinity and expression, but so far no investigation has been made concerning the effect of specific modification of a transcription factor binding site. In this study we have specifically modified the binding site of the transcription factor AP-1 with the (+)-anti- or (-)-syn-enantiomers of BPDE, and have studied how this affects the binding of the Fos-Jun proteins. Both (-)-syn- and (+)-anti-BPDE, giving rise to a cis- and a trans-adduct, respectively, have been used and, in both cases, the binding of AP-1 like proteins from HeLa cell nuclear extracts to the modified binding site decreased by approximately 50% as compared to controls. There was no apparent difference in response between the different diastereomers, so it seems that the binding geometry of the adduct (either intercalated or pointing towards the 5'-end in the minor groove, respectively) is of less importance. An interesting feature was the apparent yield of three differently shifted bands using the modified binding site. This can be due to conformational changes of the complex and/or the presence of less specific complexes as an effect of the adduct. Recombinant, truncated Fos-Jun proteins completely failed to bind to modified binding sites when performing the same experiments as detailed above and their binding to unmodified oligonucleotide was 50% less than for native proteins from the nuclear extract. Supershift assays, using antibodies specific for c-Fos and c-Jun proteins, and competition experiments with various unlabelled oligonucleotides, were performed in order to check the specificity of binding in the observed bands. The results using the oligonucleotide containing the unmodified binding sequence and HeLa cell nuclear extract were fully consistent with binding of c-Fos and c-Jun, whereas the binding to oligonucleotides containing BPDE-modified binding sequences was not. This implies involvement of other proteins in this event.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1996

Impaired effect of nitric oxide synthesis inhibition on tubuloglomerular feedback in hypertensive rats.

Experiments were conducted to compare the effects of intratubular inhibition [N omega-nitro-L-arginine (L-NNA)] of nitric oxide (NO) on the tubuloglomerular feedback (TGF) mechanism between anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) and between the Milan hypertensive (MHS) and the Milan normotensive (MNS) strains of rats. Changes in proximal tubular stop-flow pressure (Psf) in response to various loop of Henle perfusion rates and measurements of early proximal flow rate (EPFR) were used to characterize TGF. Maximal drop in Psf (delta Psf) were used to indicate TGF reactivity and the flow rate eliciting half-maximal delta Psf (turning point; TP) to indicate TGF sensitivity. Under control conditions, TGF sensitivity was significantly higher in SHR than in WKY, but, after L-NNA infusion, TP was decreased in WKY and not in SHR. L-NNA infusion increased delta Psf by 95% in WKY but to a lesser extent (by 26%) in SHR. In the same way, L-NNA decreased TP in MNS but not in MHS. The increase in delta Psf was 99% in MNS but only 32% in MHS. The EPFR reduction after TGF activation was significantly increased in WKY and MNS but relatively unchanged in SHR and MHS. The results show that the effect of intratubular NO synthase inhibition on TGF is impaired in both strains of hypertensive rats.

Animals↗
PubMed1995

Acute renal denervation causes time-dependent resetting of the tubuloglomerular feedback mechanism.

Renal effects of acute renal denervation (DNX) were studied in anaesthetized rats. In a first series, whole kidney clearance measurements were made 120 and 240 min after unilateral DNX. At 240 min, urine production was 3.59 +/- 0.87 microL min-1 in control kidneys and 7.74 +/- 1.97 microL min-1 in denervated kidneys. The corresponding values for sodium excretion were 0.56 +/- 0.17 and 1.41 +/- 0.34 mumol min-1, potassium excretion 0.48 +/- 0.08 and 0.97 +/- 0.37 mumol min-1 and glomerular filtration rate (GFR) 0.83 +/- 0.08 and 1.05 +/- 0.16 mL min-1, respectively. In a second series, tubuloglomerular feedback (TGF) characteristics were determined with the stop-flow pressure (Psf) technique. With increasing time, the sensitivity of the TGF mechanism diminished in denervated rats, as indicated by an increased turning point (TP). TP was significantly increased 2 h after DNX from 19.1 +/- 1.13 in control to 25.9 +/- 1.10 nL min-1. TP was further increased 4 h after DNX to 37.3 +/- 3.12 nL min-1. However, the maximal TGF response to increased flow in the late proximal tubule was not altered. But, Psf was significantly higher in DNX rats than in the controls (47.4 +/- 1.01 vs. 43.0 +/- 1.53 mmHg) in spite of a lower blood pressure (107 +/- 2.9 vs. 119 +/- 2.2 mmHg). We conclude that intact renal nerves are essential for the setting of the TGF sensitivity and hence the regulation of GFR.

Animals↗
PubMed1995

A new method for exchange of perfusion fluid during in vivo micropuncture.

The first step in the tubuloglomerular feedback (TGF) mechanism is postulated to be the sensing of changes in tubular NaCl concentration by the macula densa (MD) cells. Despite this, few in vivo studies using different tubular NaCl concentrations administered to the MD site have been completed. Methodological problems associated with retrograde perfusion might possibly explain this. In the present study we present a modification of a method used in in vitro tubular perfusion experiments which makes it possible to determine the TGF response using retrograde perfusion with a single perfusion pipette. The system is based on the use of a fluid exchange pipette introduced through a chamber in the holder of the perfusion pipette all the way to the tip of this pipette. The perfusion flow was regulated by a pressure head, and by regulating the outflow from the chamber. The flow was determined for different tip diameters and for different perfusion pressures. Using a tip diameter of 4 microns, the flow through the tip was in the range 18-25 nL min-1 at a pressure of 60-70 mmHg. The fluid-exchange pipette was tested in vivo by measuring proximal tubular stop-flow pressure while perfusing the macula densa region with different NaCl concentration.

Animals↗
PubMed1994

Cell calcium concentration in glomerular afferent and efferent arterioles under the action of noradrenaline and angiotensin II.

The glomerular arterioles in the juxtaglomerular apparatus seem to function as effectors of the tubuloglomerular feedback mechanism. In this mechanism increased delivery of fluid to the distal nephron activates the macula densa cells through transport via an Na-2Cl-K cotransporter. This activation may lead to vasoconstriction of the afferent arteriole. Furthermore, vasoactive substances seem to affect both afferent and efferent arterioles. There are morphological differences along the afferent arteriole, some parts containing epithelioid cells with renin granules and others regular smooth muscle cells. The aim of the present experiments was to determine whether noradrenaline (10(-6) M) and angiotensin II (10(-6) M) had differential effects on the cell calcium concentration [Ca2+]i and on contraction in isolated perfused afferent and efferent arterioles and in the mesangial region. [Ca2+]i was measured with fura-2, an intensified videocamera and a digital imaging system. From the proximal to the distal part of the arteriole [Ca2+]i increased from about 100 to 250 nM. A [Ca2+]i increase and a contraction were caused by noradrenaline alone in the proximal part of the afferent arteriole and by angiotensin II alone in the distal part of this arteriole. In the mesangial region there was a high basal [Ca2+]i but no response to the vasoactive substances. In the efferent arteriole, application of both noradrenaline and angiotensin II led to an increase in [Ca2+]i and a contraction. The present experiments indicate that the two vasoactive substances tested act in a similar fashion along the whole length of the efferent arteriole, while in the afferent arteriole their actions are not equally distributed.

Angiotensin II↗
PubMed1994

Inhibition of locally produced nitric oxide resets tubuloglomerular feedback mechanism.

This study was designed to compare the effects of systemic and intratubular infusions of the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine (L-NNA) on the tubuloglomerular feedback (TGF) mechanism in anesthetized rats. We recently showed that intravenous infusion of L-NNA led to increases in mean arterial blood pressure (Pa), proximal tubular stop-flow pressure (Psf), and enhanced TGF sensitivity and reactivity. To avoid major systemic effects, in this study TGF was studied after intratubular NO inhibition. Intratubular infusion of L-NNA (10(-3) M) yielded similar results as shown with intravenous infusion, without systemic effects. TGF sensitivity and reactivity were increased, indicated by decreased turning point (TP) from 19.8 +/- 1.0 to 15.2 +/- 0.7 nl/min and increased delta Psf from 10.0 +/- 0.8 to 23.9 +/- 1.9 mmHg (24.3 vs. 59.1%). L-NNA at a concentration of 10(-4) M showed significant changes in both TP (from 20.9 +/- 1.1 to 17.8 +/- 1.0 nl/min) and delta Psf (from 7.6 +/- 0.6 to 13.9 +/- 0.7 mmHg), whereas 10(-5) M only increased delta Psf (9.7 +/- 1.0 vs. 12.1 +/- 1.1 mmHg). However, at low tubular perfusion rates Psf was not influenced by L-NNA. The early proximal flow rate (EPFR) showed no change at low tubular perfusion rates with L-NNA. At maximal TGF activation (40 nl/min), delta EPFR was increased from 34% in control to 62%. Our results suggest that NO not only regulates glomerular capillary pressure but also decreases the sensitivity of the TGF mechanism.

Amino Acid Oxidoreductases↗
PubMed1993

The cytosolic chloride concentration in macula densa and cortical thick ascending limb cells.

It is believed that chloride transport through the macula densa (MD) cells is a factor involved in the tubuloglomerular feedback (TGF) mechanism and in MD-mediated renin release. In this study isolated and perfused rabbit kidney cortical thick ascending limb (cTAL) segments containing MD plaques and attached glomeruli were loaded with chloride (CL-sensitive) 6 methoxy-1-fluorophore (sulphanate-propyl) quinolinium (SPQ). MD and cTAL intracellular chloride concentration ([Cl-]i) was determined by using image-intensified video microscopy and digital image-processing for measuring the intensity of the emitted SPQ fluorescence. With 150 mM NaCl in lumen and bath the [Cl-]i in MD and cTAL cells was 58.8 +/- 7.2 mM (n = 20) and 68.7 +/- 9.8 mM (n = 14), respectively. When the presumed luminal Na(+)-2Cl(-)-K+ co-transporter was blocked by adding 10(-4)M furosemide, the [Cl-]i was reduced in both, MD and cTAL cells from 55.5 +/- 11.9 to 28.6 +/- 10.0 mM (n = 10) and from 43.8 +/- 2.6 to 13.1 +/- 4.5 mM (n = 5), respectively. A reduction in luminal NaCl from 150 to 30 mM also decreased both, MD and cTAL [Cl-]i from 69.4 +/- 9.1 to 36.5 +/- 5.1 mM (n = 9) and from 82.9 +/- 14.5 to 49.4 +/- 8.0 mM (n = 8), respectively. Basolateral addition of the Cl(-)-channel blocker NPPB increased MD [Cl-]i from 31.1 +/- 2.0 to 100.7 +/- 17.0 mM (n = 5) and cTAL [Cl-]i from 44.4 +/- 12.9 to 89.7 +/- 11.7 mM (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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↗