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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
PubMed2001

Pressure flow measurement of hydronephrosis in children: a new approach to definition and quantification of obstruction.

PURPOSE: Hydronephrosis due to obstruction of the ureteropelvic junction is not uncommon in children. The critical level of outflow resistance characterizing obstruction remains to be established. It was previously found in our laboratory that the outflow resistance could be calculated in an animal model by servoregulating the infused flow to preset pressure levels. We determine whether this procedure is also feasible in patients with hydronephrosis. MATERIALS AND METHODS: A total of 46 patients with 48 hydronephrotic kidneys were examined. There were 32 boys and 14 girls with a diagnosis of hydronephrosis and suspected ureteropelvic junction obstruction who underwent a pressure flow study under general anesthesia for evaluation before possible surgery. The kidney was punctured percutaneously under ultrasonic guidance, and the study was performed under fluoroscopy. Flow levels were measured when steady state flow was achieved at pressures 5, 10, 15, 20, 25 and 30 mm. Hg greater than the intra-abdominal pressure. A conventional Whitaker test at an infusion rate of 10 ml. per minute was performed for comparison. The patient then underwent pyeloplasty if the kidney was considered obstructed. RESULTS: There were 2 patients excluded from evaluation because of significant leakage of contrast medium. Stable and repeatable recordings were obtained in all pressure flow studies but only in 7 of 46 Whitaker tests. A total of 41 kidneys were considered obstructed at pressure flow studies and operated on. The resistance was pressure dependent. Thus, mean resistance in the previous range 5 to 15 mm. Hg was considered a good overall measure of outflow resistance. Mean resistance less than 0.75 was normal and greater than 1.25 obstruction. There were 7 patients who had crossing vessels and a high mean resistance (3 or greater). CONCLUSIONS: The Whitaker test proved to be of no value for calculating the outflow resistance in ureteropelvic junction obstruction. The pressure flow study is superior to the Whitaker test for determining the outflow resistance and also allowing categorization of ureteropelvic junction obstruction.

Child↗
PubMed2001

Effects of long-term inhibition of neuronal nitric oxide synthase on blood pressure and renin release.

Nitric oxide (NO) produced by neuronal NO-synthase (nNOS) in macula densa cells may be involved in the control of renin release. 7-Nitro indazole (7-NI) inhibits nNOS, and we investigated the effect of short- (4 days) and long-term (4 weeks) 7-NI treatment on blood pressure (BP), plasma renin concentration (PRC) and glomerular filtration rate (GFR) in rats on different salt diets. Rats were divided into three groups and given low-salt (LS), normal (C) and high-salt (HS) diets. Each diet group was subdivided into two groups treated either with 7-NI or vehicle. Long-term 7-NI-treated rats (LS and C) showed increased BP compared with controls (LS: 149 +/- 4 vs. 133 +/- 3; C: 146 +/- 4 vs. 127 +/- 4 mmHg). Blood pressure in HS rats did not differ from that in controls. Plasma renin concentration was stimulated in LS-rats (251 +/- 64 mGU mL(-1)) compared with C and HS rats (42 +/- 8 and 39 +/- 5 mGU mL(-1), respectively) but was not significantly affected by chronic 7-NI treatment (350 +/- 103, 49 +/- 10 and 50 +/- 15 mGU mL(-1) in LS, C and HS, respectively). In rats treated with 7-NI for 4 days, no effect on BP was seen, but PRC was increased in 7-NI treated LS rats compared with vehicle treated LS rats (107 +/- 15 vs. 56 +/- 1 mGU mL(-1)). Stimulation of PRC in LS rats was further enhanced by 7-NI after 4 days of treatment, but not affected in rats treated for 4 weeks. This suggests that inhibition of nNOS stimulates renin release but that this stimulatory effect in the long run might be depressed by the increase in blood pressure.

Administration, Oral↗
PubMed2001

Effect of thromboxane and nitric oxide blockade on renal blood flow increase during volume expansion in hydronephrotic rats.

OBJECTIVE: It has recently been found that hydronephrotic rats, despite low diuresis, show a significant increase in renal blood flow (RBF) during volume expansion. The present experiments were designed to evaluate the mechanisms underlying this phenomenon. MATERIAL AND METHODS: Three-week-old Sprague-Dawley rats underwent partial obstruction of the left ureter using the Ulm-Miller psoas groove technique. The effects on RBF were studied 3 weeks later under general anesthesia using real-time ultrasound flowmetry, first during normohydration and then during extracellular volume expansion, in both untreated animals, and after prior blockade of either thromboxane or nitric oxide. RESULTS: Significant hydronephrosis developed in all cases. RBF was normal under control conditions. During volume expansion RBF increased significantly in untreated experimental animals (mean 7.5%). In contrast to this finding, RBF remained unchanged during volume expansion in both the thromboxane and nitric oxide blockade groups. CONCLUSION: It is concluded that a thromboxane- and/or nitric oxide-dependent RBF redistribution takes place in hydronephrotic kidneys during volume expansion.

Animals↗
PubMed2001

Abolished tubuloglomerular feedback and increased plasma renin in adenosine A1 receptor-deficient mice.

The hypothesis that adenosine acting on adenosine A1 receptors (A1R) regulates several renal functions and mediates tubuloglomerular feedback (TGF) was examined using A1R knockout mice. We anesthetized knockout, wild-type, and heterozygous mice and measured glomerular filtration rate, TGF response using the stop-flow pressure (P(sf)) technique, and plasma renin concentration. The A1R knockout mice had an increased blood pressure compared with wild-type and heterozygote mice. Glomerular filtration rate was similar in all genotypes. Proximal tubular P(sf) was decreased from 36.7 +/- 1.2 to 25.3 +/- 1.6 mmHg in the A1R+/+ mice and from 38.1 +/- 1.0 to 27.4 +/- 1.1 mmHg in A1R+/- mice in response to an increase in tubular flow rate from 0 to 35 nl/min. This response was abolished in the homozygous A1R-/- mice (from 39.1 +/- 4.1 to 39.2 +/- 4.5 mmHg). Plasma renin activity was significantly greater in the A1R knockout mice [74.2 +/- 14.3 milli-Goldblatt units (mGU)/ml] mice compared with the wild-type and A1R+/- mice (36.3 +/- 8.5 and 34.1 +/- 9.6 mGU/ml), respectively. The results demonstrate that adenosine acting on A1R is required for TGF and modulates renin release.

Adenosine↗
PubMed2001

Renal blood flow increase during volume expansion in hydronephrotic rats.

PURPOSE: We assessed the renal blood flow pattern in experimental hydronephrosis during normal hydration and extracellular volume expansion. MATERIALS AND METHODS: Partial obstruction of the left ureter was created in 3-week-old Sprague-Dawley rats by embedding the ureter in a psoas muscle groove. Moderate hydronephrosis without kidney weight reduction developed in all cases. The effects on renal hemodynamics were studied with real-time ultrasound flowmetry 3 weeks later during normal hydration and then during volume expansion. The degree of hydronephrosis was classified as mild, moderate or severe. RESULTS: Under baseline conditions renal blood flow was normal in mild and moderate hydronephrosis but low in severe hydronephrosis. During volume expansion renal blood flow increased significantly in all experimental animals (mean 14%) compared to that in controls, which remained unaffected or decreased (mean -3%). The flow increase was related to the degree of dilatation, which was 2% in mild, 13% in moderate and 44% in severe hydronephrosis when the groups were considered separately. CONCLUSIONS: A significant increase in renal blood flow proportional to the degree of hydronephrosis occurred as a result of volume expansion. This finding may be explained by a state of vasodilatation combined with a reduction in the filtration coefficient.

Animals↗
PubMed2000

Analysis of p53 mutations in single cells obtained from histological tissue sections.

We have previously reported on direct sequence analysis of the p53 gene in laser-dissected single cells from tissue sections, where each allele of two fragments (exons 7 and 8) could be accurately analyzed in only 14% of the cells due to the high frequency of exon and allele dropout. Here in an effort to minimize this problem, we have investigated various approaches for sample preparation and gene amplification. By pinpointing some critical steps in the procedure, we could increase the number of investigated exons and substantially improve the genetic analysis of single cells obtained from histochemically stained frozen tissue sections. The biggest improvement was achieved by minimizing DNA degradation using EDTA as a nuclease inhibitor in all sample preparation steps. Efforts to increase primer annealing, by increasing the concentration of template and primers, in addition to prolonging the annealing and extension times, also improved the amplification efficiency. With these measures we can now amplify six individual exons of the p53 gene (exons 4-9) in 70% of the cells and in 50% of these cells both alleles are amplified. This allows application of the method in various investigations such as within the field of tumor pathology.

Alleles↗
PubMed2000

The influence of beta-adrenergic activation on noradrenergic alpha1 activation of rabbit afferent arterioles.

The aim of the present investigation was to examine the effect of beta-adrenergic stimulation on smooth muscle calcium concentration ([Ca2+]i) in resting conditions and after administration of norepinephrine (NE) to stimulate alpha-adrenoceptors in isolated rabbit afferent arterioles loaded with the calcium-sensitive fluorescent probe fura-2. [Ca2+]i was evaluated in the proximal and distal parts of the arterioles. NE (4x10(-7) M) increased [Ca2+]i in both these regions. The alpha1-adrenoceptor antagonist prazosin (10(-7) M) totally abolished the NE-induced increase in [Ca2+]i, while the alpha2-adrenoceptor antagonist yohimbine (5x10(-7) M) had no influence on the response to NE. When beta-adrenoceptors were stimulated, using isoproterenol (10(-7) M), the NE-induced increase in [Ca2+]i was significantly lower in both regions. Activation of beta-adrenoceptors with isoproterenol did not affect the [Ca2+]i increase in response to depolarization with K+. Since beta-adrenoceptor stimulation raises the smooth muscle cell levels of cAMP, an adenylate cyclase stimulator, forskolin (10(-5) M) was administered prior to NE application. This maneuver also blunted the increase in [Ca2+]i in both regions. We conclude that the calcium response to NE in the isolated rabbit afferent arteriole is mediated by an alpha1-adrenoceptor. beta-Adrenoceptor stimulation and forskolin blunt the increase in [Ca2+]i induced by NE stimulation, indicating that cAMP counteracts the NE-induced activation of alpha1-adrenoceptors.

Adenylyl Cyclases↗
PubMed2000

Impaired effect by NO synthase inhibition on tubuloglomerular feedback in rats after chronic renal denervation.

Acute unilateral renal denervation (aDNX) is associated with reduced tubuloglomerular feedback (TGF) sensitivity. Six days after denervation (cDNX) TGF sensitivity is somewhat restored, but TGF reactivity increased. This study aimed to investigate if the increased TGF reactivity that was seen in cDNX kidneys was owing to reduced production of nitric oxide (NO). TGF characteristics were determined with micropuncture experiments in anaesthetized rats, using the stop-flow pressure (PSF) technique. Maximal drop in PSF (DeltaPSF) was used as an index of TGF reactivity and the loop of Henle perfusion rate that elicited half-maximal DeltaPSF, the turning point (TP) was used as a measure of TGF sensitivity. In cDNX kidneys, TP was higher than in control rats (25.4 +/- 1.5 nL min-1 vs. 19.1 +/- 1.1 nL min-1), but clearly lower than in aDNX rats (37. 3 +/- 3.1 nL min-1). TGF was more reactive in cDNX rats (DeltaPSF=14. 7 +/- 1.1 mmHg) than in aDNX (7.9 +/- 1.1 mmHg) and control rats (9. 6 +/- 0.9 mmHg). Intratubular inhibition of NO synthase N omega-nitro-L-arginine (L-NA) in sham-DNX animals, decreased TP to 13.9 +/- 2.2 nL min-1 and DeltaPSF was increased with 92%. In cDNX kidneys TP was not significantly reduced by L-NA, and TGF reactivity was only moderately increased by 31%. Intratubular infusion of L-arginine (L-Arg) reduced DeltaPSF from 10.2 +/- 0.7 to 6.5 +/- 0.6 mmHg in sham-DNX kidneys, but TP was unaffected. In cDNX kidneys, there was no effect on either DeltaPSF or TP by the addition of L-Arg. However, when NO was delivered via sodium nitroprusside in the tubular perfusate, a clear reduction of DeltaPSF was seen in both sham-DNX and cDNX kidneys (from 9.9 +/- 0.5 to 4.4 +/- 1.0 and from14.9 +/- 1.3 to 8.1 +/- 1.5 mmHg, respectively). This indicates that cDNX is a state of low renal NO production and that this low level of NO resets TGF to a higher sensitivity and more pronounced reactivity.

Animals↗
PubMed2000

Renal NO production and the development of hypertension.

The juxtaglomerular apparatus (JGA) has the very important functions of detecting the fluid flow rate to the distal tubule and thus controlling the glomerular filtration rate (GFR) (tubuloglomerular feedback mechanism [TGF]) and renin release from the afferent arteriole. In studies of the TGF it has been evident that the sensitivity of this mechanism can be reset. Volume expansion will reset it to a low sensitivity leading to a high GFR and urine excretion rate, while dehydration will sensitize the TGF mechanism, giving rise to a low GFR and low urine excretion rate. Furthermore, we have found that in animals that spontaneously develop hypertension there is initially a sensitization of the TGF, leading to a reduced GFR and urine excretion rate, with fluid volume retention in the body and a consequent rise in blood pressure. When the pressure is raised, the TGF characteristics are normalized. In the macula densa (MD) cells in the JGA, there is a large production of NO from neuronal NOS. This production continuously reduces TGF sensitivity and is apparently impaired in animals that spontaneously develop hypertension. When we added an nNOS inhibitor to the drinking water for several weeks while measuring blood pressure, we found an increase in blood pressure after 3-4 weeks of treatment. This effect was abolished by a high salt diet. From these investigations, it also appeared as if nNOS-derived NO inhibited renin release. Experiments have also indicated that NO may resensitize inhibited G-protein coupled purinergic receptors.

Animals↗
PubMed2000

Constitutive nitric oxide synthesis in the kidney--functions at the juxtaglomerular apparatus.

Tubulo-vascular information transfer at the renal juxtaglomerular apparatus (JGA) serves to adjust the biosynthesis and release of renin, the key enzyme of the renin angiotensin system, and to regulate glomerular arteriolar muscle tone. The macula densa serves as a sensor of tubular NaCl. Concentration-dependent salt uptake through the Na-K-2Cl cotransporter located in the apical membrane of macula densa cells triggers a signal transduction cascade that involves the synthesis of nitric oxide (NO) through a type 1 NO synthase (NOS1) which is described with respect to its complex mRNA structure and regulatory aspects. The anatomical and functional targets of the NO-soluble guanylyl cyclase-cGMP pathway at the JGA are reviewed.

Animals↗
PubMed1999

Calcium response to adenosine and ATP in rabbit afferent arterioles.

The effects of purine compounds in the renal vasculature are almost exclusively restricted to pre-glomerular vessels. Although their physiological role as extracellular messengers is not clear, there are extensive data indicating the importance of adenosine and ATP in the regulation of renal haemodynamics. This study was undertaken to characterize the calcium response of rabbit afferent arteriole to adenosine, ATP and other nucleotides. Experiments were performed in isolated afferent arterioles, microdissected from rabbit kidneys and loaded with fura-2. Intracellular calcium concentration ([Ca2+]i) was measured by video in proximal and distal parts of the afferent arteriole. Application of 100 microM adenosine or ATP increased [Ca2+]i in both arteriolar regions. In all cases the response had two well distinguishable phases: a quick peak increase and a plateau phase that equilibrated at a [Ca2+]i significantly higher than the basal level. UTP (100 microM) had no effect on the arteriole. Removal of extracellular calcium (2.5 mM EGTA) abolished only the plateau phase in response to adenosine, without significantly changing the peak increase. In contrast, the response to ATP was completely abolished in both arteriolar regions, where [Ca2+]i decreased upon application of the agonist and rapidly increased after restoration of calcium concentration to plasma level. We conclude that P1 and P2X receptors are present along the rabbit afferent arteriole and mediate calcium mobilization, with the same distribution in the proximal and distal segments.

Adenosine↗
PubMed1999

Oxygen-dependent inhibition of respiration in isolated renal tubules by nitric oxide.

BACKGROUND: The partial pressure (tension) of oxygen (PO2) in the kidney medulla has been established to be lower than that of the cortex. The kidney medulla has been shown to be particularly sensitive to hypoxia. However, the measured PO2 in the kidney medulla is sufficient to support maximal respiration. It has been recently shown that endogenously produced nitric oxide (NO) may inhibit oxygen consumption in the kidney. We studied whether NO plays a role in hypersensitivity of the kidney medulla to hypoxia. METHODS: We studied the effect of added NO on isolated cortical and outer medullary renal tubules in simultaneous oxygen consumption and NO measurements at different oxygen concentrations. RESULTS: We found that NO could potently and reversibly inhibit respiration at nanomolar concentrations. The inhibitory effect of NO was markedly increased at low physiological oxygen concentrations. The effect of NO was cGMP independent because the selective guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) at a 10 microM concentration had no effect on basal or NO-inhibited respiration. The value for half-maximal NO-mediated inhibition of respiration was virtually identical to that found in isolated mitochondria, and therefore, NO was most likely directly acting on mitochondria. Interestingly, we found no differences in sensitivity to NO-mediated inhibition between outer medullary and cortical tubules. CONCLUSIONS: We suggest that because of its low PO2, the renal outer medulla is more sensitive to hypoxia, not because of the low PO2 as such, but probably because of the competition between NO and oxygen to control respiration.

Adenosine Triphosphate↗
PubMed1998

Renal nerve stimulation restores tubuloglomerular feedback after acute renal denervation.

Renal nerves play an important role in the setting of the sensitivity of the tubuloglomerular feedback (TGF) mechanism. We recently reported a time-dependent resetting of TGF to a lower sensitivity 3-4 h after acute unilateral renal denervation (aDNX). This effect persisted after 1 week, but was then less pronounced. To determine whether normal TGF sensitivity could be restored in aDNX kidneys by low-frequency renal nerve stimulation (RNS), the following experiments were performed. Rats with aDNX were prepared for micropuncture. In one experimental group proximal tubular free flow (Pt) and stop flow pressures (Psf) were measured during RNS at frequencies of 2, 4 and 6 Hz. In another series of experiments the TGF sensitivity was evaluated from the Psf responses at different loop perfusion rates after 20 min of RNS at a frequency of 2 Hz. The maximal drop in Psf (delta Psf) and the tubular flow rate at which half the maximal response in delta Psf was observed (turning point, TP), were recorded. At RNS frequencies of 2, 4 and 6 Hz, Pt decreased from the control level of 14.1 +/- 0.8-13.1 +/- 1.0, 12.4 +/- 1.1 and 11.2 +/- 0.8 mmHg (decrease 21%, P < 0.05), respectively, while at zero perfusion and during RNS at 2 and 4 Hz Psf decreased from 42.5 +/- 1.6 to 38.2 +/- 1.4 and 32.8 +/- 4.3 mmHg (decrease 23%, P < 0.05), respectively. The TGF characteristics were found to be reset from the normal sensitivity with TP of 19.0 +/- 1.1 nL min-1 and delta Psf of 8.7 +/- 0.9 mmHg to TP of 28.3 +/- 2.4 nL min-1 (increase 49%, P < 0.05) and delta Psf of 5.8 +/- 1.2 mmHg (decrease 33%) after aDNX. After 20 min of RNS at 2 Hz TP was normalized and delta Psf was 33% higher. Thus the present findings indicate that the resetting of the TGF sensitivity that occurred 2-3 h after aDNX could be partially restored by 20 min of RNS at a frequency of 2 Hz. These results imply that renal nerves have an important impact on the setting of the sensitivity of the TGF mechanism.

Animals↗
PubMed1998

Hypertension and impaired renal angiotensin II response in rats after chronic neuronal nitric oxide synthase inhibition.

Nitric oxide (NO) produced by the macula densa cells is important for the control of tubuloglomerular feedback (TGF). Reduced production of NO by these cells activates TGF and could result in hypertension, although the TGF activity is then normalized in the hypertensive state. The normalization of TGF in this form of hypertension might be explained by an impaired ability of angiotensin II to constrict renal vessels or by up-regulation of some other vasodilator not affected by NO synthase inhibitors.

Angiotensin II↗
PubMed1998

Nitric oxide and renal blood pressure regulation.

In the mammalian body the kidney might be the most important organ for long-term blood pressure regulation. Nitric oxide seems to play a particular role in the control of renal haemodynamics, and changes in renal nitric oxide synthesis should therefore be of great importance for the renal control of blood pressure.

Animals↗
PubMed1997

Increased blood pressure in rats after long-term inhibition of the neuronal isoform of nitric oxide synthase.

In the kidney, nitric oxide synthase (NOS) of the neuronal isoform (nNOS) is predominantly located in the macula densa cells. Unspecific chronic NOS inhibition in rats leads to elevated blood pressure (P(A)), associated with increased renal vascular resistance. This study was designed to examine the effect of chronic selective inhibition of nNOS with 7-nitro indazole (7-NI) on P(A), GFR, and the tubuloglomerular feedback (TGF) system. P(A) was repeatedly measured by a noninvasive tail-cuff technique for 4 wk in rats treated orally with 7-NI, and in control rats. After treatment, the animals were anesthetized and renal excretion rates, GFR, and TGF activity were determined. After 1 wk of 7-NI treatment P(A) was increased from 129+/-4 to 143 2 mmHg. GFR (1.85+/-0.1 vs. 1.97+/-0.2 ml/min in controls) was unchanged, but micropuncture studies revealed a more sensitive TGF than in controls. After 4 wk of 7-NI treatment P(A) was 152+/-4 mmHg, but no change in GFR (1.90+/-0.5 ml/min) or TGF sensitivity was detected. Acute administration of 7-NI to nontreated rats did not affect P(A), but decreased GFR (1.49+/-0.1 ml/min) and increased TGF sensitivity. In conclusion, chronic nNOS inhibition leads to increased P(A). Our results suggest that the elevated P(A) could be caused by an initially increased TGF sensitivity, leading to decreased GFR and an increased body fluid volume.

Animals↗
PubMed1997

Effect of inhibition of pentagastrin-stimulated acid secretion on gastric mucosal gland luminal pressure.

We demonstrated previously that hydrochloric acid secreted from the gastric glands traverses the mucus layer in channels above the gland openings. The driving force for creation of these channels is most probably the hydrostatic pressure generated in the gastric gland lumen during stimulation of acid secretion. Here we investigated the effect of total inhibition of acid secretion on gland luminal pressure. Glandular pressure was measured in vivo with a pressure-sensitive microelectrode technique in Inactin-anaesthetized Sprague Dawley or Lewis x DA F1 rats. Glandular pressure was significantly reduced after ranitidine inhibition of acid secretion, from 17.2 +/- 2.1 mmHg during pentagastrin stimulation to 11.2 +/- 1.2 mmHg. This was also true when pentagastrin infusion was continued after inhibition of secretion with ranitidine. Omeprazole, however, did not significantly alter gland luminal pressure although it totally inhibited acid secretion. With continuation of pentagastrin infusion after omeprazole inhibition, glandular pressure increased significantly from 17.6 +/- 3.4 to 20.1 +/- 3.3 mmHg. In conclusion, total inhibition of acid secretion with ranitidine reduces but does not abolish gland luminal pressure. After omeprazole inhibition of acid secretion the gastric gland luminal pressure persisted or even increased. Since the volume secretion is lower after omeprazole administration than during pentagastrin stimulation, the outflow resistance most probably had increased after omeprazole injection. Suggestions for increased outflow resistance are narrowing in the upper part of the gland lumen by conformational changes of the cells or muscle contractions, and/or an increase in mucus secretion or viscosity.

Animals↗