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R Unwin

Publications and source records attributed to R Unwin.

At least 19 recordsLinked to original sources
PubMed2000

Blood pressure and Turner syndrome.

INTRODUCTION: Elevated blood pressure (BP) is an important predictor of morbidity and mortality from cardiovascular disease. Patients with Turner syndrome (TS) have a higher morbidity and mortality in middle age than the normal population. As BP in childhood or early adulthood is predictive of BP later in adult life, we assessed manual and 24 h ambulatory BP in patients with TS to determine whether the BP pattern is altered at an early stage in these patients who are known to be at risk of cardiovascular disease. PATIENTS AND METHODS: We studied manual and 24 h ambulatory BP profiles in 75 girls with Turner syndrome, age range 5.4-22.4 years. A monitor with an oscillometric device (SpaceLabs model 90207) and an appropriate sized cuff was used. BP was measured during the day-time (0800-2000 h) and the night-time periods (2200-0800 h). The BP measured were compared with population standards. The effect of different growth promoting agents on BP was also evaluated. RESULTS: Mean manual and 24 h ambulatory BP measurements were 118/77 mmHg (range 95/60-140/102) and 115/70 mmHg (range 93/57-154/99), respectively. There was minimal difference between the two methods with a positive bias of 2.4 mmHg for diastolic BP and a negative bias of 2.1 mmHg for systolic BP. The mean standard deviation scores (SDS) corresponding to the mean BP recordings were 24 h systolic + 0. 81 (range - 1.26 to + 4.45), 24 h diastolic + 0.43 (range - 0.85 to + 3.42), day-time systolic + 1.08 (range - 0.95 to + 4.72), day-time diastolic + 0.70 (range - 0.94 to + 3.71), night-time systolic + 0. 22 (range -2.2 to + 3.64) and night-time diastolic - 0.18 (range -2. 0 to + 2.43). The SDS for both the mean 24 h and day-time systolic and diastolic BP were shifted to the right of the normal distribution. 57% of the girls had less than the normal 10% reduction in nocturnal systolic blood pressure. 17% had diastolic and 21% had systolic blood pressure above the 95th percentile for age and sex. There was no significant difference in the BP SDS between girls on no treatment and those receiving treatment. CONCLUSION: Over 50% of girls with Turner syndrome have an abnormal BP circadian rhythm, which is similar to adult patients with secondary hypertension. Patients with Turner syndrome have higher blood pressure measurements compared to published population standards, as evidenced by the shift to the right of both the systolic and diastolic BP SDS. These findings suggest that girls with Turner syndrome should be carefully monitored in childhood and adulthood for blood pressure and other cardiovascular risk factors.

Adolescent↗
PubMed2000

The influence of renal and cardiovascular abnormalities on blood pressure in Turner syndrome.

INTRODUCTION: Patients with Turner syndrome (TS) are at an increased risk of morbidity and mortality from cardiovascular disease. This study was undertaken to establish the prevalence of hypertension in patients with TS and to establish to what extent cardiovascular or renal abnormalities contribute to the measured blood pressure. PATIENTS AND METHODS: 62 patients with TS, age 5.4-22.4 years, had 24 h-ABPM (ambulatory blood pressure monitoring), echocardiography, renal imaging and measurement of recumbent plasma renin activity (PRA). Blood pressure was compared with population standards. RESULTS: 21% of the TS study population had mean systolic and 17% mean diastolic 24 h-ABPM measurements above the 95th percentile for age and sex (i.e. mild hypertension). Borderline blood pressure (i.e. 90th to 95th percentile) was found in another 17% of the patients. 57% of the patients had a blunted (i.e. less than 10%) fall in the night-time blood pressure. 24% of the patients had a detectable cardiac abnormality, 42% a detectable renal abnormality and 52% were found to have raised plasma renin activity. The presence of a cardiac or renal abnormality had no significant effect on blood pressure. Blood pressure of patients on growth and/or pubertal therapy was not different from those patients on no such treatment. CONCLUSION: Over 30% of patients with Turner syndrome were found to be mildly hypertensive and over 50% had an abnormal diurnal blood pressure profile. In this study we were unable to demonstrate that the presence of renal or cardiac abnormalities had an effect on recorded blood pressure. The use of growth hormone and oestrogen to manage growth failure and pubertal delay did not seem to affect blood pressure. This study suggests that there is a high prevalence of raised blood pressure in Turner syndrome patients. The 24 h-ambulatory blood pressure monitoring profile suggests that this may be secondary in origin, but we were unable to demonstrate an underlying mechanism with the renal and cardiac investigations performed.

Adolescent↗
PubMed2000

Induction of proliferation and apoptotic cell death via P2Y and P2X receptors, respectively, in rat glomerular mesangial cells.

BACKGROUND: Cell surface receptors for adenosine 5'-triphosphate (ATP; P2 receptors) have been subdivided into two families: ligand-gated ion channels (P2X1-7) and G-protein-coupled (P2Y1-8) receptors. We investigated the potential role of P2 receptors on rat glomerular mesangial cells. METHODS: To investigate cell proliferation, DNA synthesis was assayed by measuring [3H]thymidine incorporation into DNA. For detecting apoptosis, morphological features, DNA fragmentation, and exposure of phosphatidylserine on the outside surface of the cell membrane were investigated. Expression of mRNA and distribution of receptors were detected by reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. RESULTS: ATP triggered a dose-dependent increase in DNA synthesis. This response was also induced by uridine triphosphate (UTP), an agonist equipotent with ATP at P2Y2 and P2Y4 receptors; both P2Y2 and P2Y4 mRNA are expressed in glomerular mesangial cells and isolated glomeruli. In contrast, the P2X7 receptor agonist 2'-83'-O-(4-benzoyl benzoyl) ATP (BzATP) caused a decrease in cell number. BzATP produced DNA cleavage and exposure of phosphatidylserine on the outside of the cell membrane. P2X7 receptors were distributed heterogeneously in unstimulated cells. The expression of P2X7 mRNA was maintained at a low level, but was induced by tumor necrosis factor-alpha. CONCLUSIONS: Stimulation of glomerular mesangial cells via P2Y2 and/or P2Y4 and via P2X7 receptors can induce proliferation and apoptotic cell death, respectively. The balance between proliferation and apoptosis will depend on the relative stimulation and expression of these P2 receptor subtypes, and could play an important role in normal and abnormal glomerular function.

Adenosine Triphosphate↗
PubMed2000

Inhibition of neutral endopeptidase potentiates the effects of atrial natriuretic peptide on acute cyclosporin-induced nephrotoxicity.

BACKGROUND: The use of cyclosporin A (CyA) is limited by its significant nephrotoxicity. Atrial natriuretic peptide (ANP) has been shown to ameliorate the reduction in glomerular filtration rate (GFR) induced by CyA, but its effect is transient. One explanation may be the rapid breakdown of this hormone by neutral endopeptidase (NEP) which is highly active in the kidney. In the present study, we examined the effect of the NEP inhibitor thiorphan on the acute fall in GFR induced by CyA. METHODS: After a first set of experiments to investigate the renal hemodynamic effects of CyA (20 mg.kg(-1), i.v. bolus), we studied four additional conditions where acute CyA treatment was followed by the administration of: (2) ANP alone (10 microg.kg(-1) i.v. as bolus and a maintenance infusion of 1 microg. kg(-1).min(-1)); (3) thiorphan alone (5 mg.kg(-1) i.v. as bolus and a maintenance infusion of 0.5 mg.kg(-1). min(-1)); (4) ANP plus thiorphan (as in 2 and 3), and (5) an infusion of 0.9% saline, increased from 1.2 to 3 ml.h(-1). The GFR was measured as the clearance of (3)H-methoxyinulin (ml.min(-1).100 g(-1) body weight). RESULTS: The data show: (1) the GFR fell from 1.06 +/- 0.15 to 0.59 +/- 0.09 ml.min(-1).100 g(-1) (p < 0.01) 60 min after CyA and remained depressed for at least 2 h; (2) ANP caused a marked initial rise in GFR from 0.49 +/- 0.07 to 1.23 +/- 0.18 ml.min(-1).100 g(-1) (p < 0.005 vs. CyA) which declined rapidly to the value seen after CyA injection alone, despite continuing ANP infusion; (3) thiorphan caused a modest, but significant increase in GFR within 15 min from 0.48 +/- 0.04 to 0.69 +/- 0.10 ml.min(-1).100 g(-1) (p < 0.05 vs. CyA) which was sustained during infusion and for at least 30 min after stopping infusion; (4) ANP plus thiorphan produced a marked increase in GFR from 0.58 +/- 0.09 to 1.39 +/- 0.44 ml.min(-1).100 g(-1) (p < 0.05 vs. CyA) which then decreased, but remained above the post-CyA injection value, until infusion of both drugs ended; (5) more than doubling the saline infusion rate per se had no significant effect on the GFR response to CyA. The blood pressure decreased significantly during ANP infusion, but more so when combined with thiorphan. CONCLUSION: These data indicate that the inhibition of NEP by thiorphan is able to ameliorate partially the reduction in GFR induced by CyA and to enhance, and prolong, the vasodilator and diuretic effects of ANP.

Acute Disease↗
PubMed1999

An automated technique for the simultaneous determination of cations in nanoliter volumes.

BACKGROUND: The study of ion transport along the renal tubule in vivo or in vitro requires a technique capable of analyzing ion concentrations in sample volumes of only a few nanoliters. This article describes a method for the analysis of cations at physiological concentrations in samples of tubular fluid taken from single renal tubules in vivo. Method. A background electrolyte composed of 2-[N-Morpholino] ethane-sulfonic acid (MES) (50 mmol/liter) and L-histidine (50 mmol/liter; pH congruent with 6.2), with the additives 18-crown-6 (1 mmol/liter) and methanol (30%) was used for the cation separation combined with conductivity detection. RESULTS: Capillary zone electrophoresis was used to separate NH4, K, Na, Ca, Li, Mg, and Ba in six minutes. Simultaneous quantitative analysis was performed for sodium and potassium, providing detection limits of 0.2 pmol for sodium and 30 fmol for potassium. The calibration plots were linear over three orders of magnitude, including the range of interest to clinical analysis. Data on the reproducibility and repeatability of peak areas and of the repeatability of migration times are reported. CONCLUSION: The results for sodium and potassium are in close agreement with those obtained by atomic absorption spectrometry, indicating that this is a suitable technique for the routine measurement of these cations in tubule fluid samples.

Automation↗
PubMed1999

The relationship between distal tubular proton secretion and dietary potassium depletion: evidence for up-regulation of H+ -ATPase.

BACKGROUND: Dietary potassium depletion is associated with elevated plasma bicarbonate concentration and enhanced bicarbonate reabsorption in the distal tubule. The relationship between distal proton secretion and potassium status was investigated by in vivo microperfusion of the superficial distal tubule. METHODS: Experiments were performed on anaesthetized rats that had been maintained on either a low-potassium or control diet for 3-5 weeks prior to experimentation. The distal tubules were perfused at 10 nl/min with either a standard or a barium chloride-containing solution, and the late distal tubular transepithelial potential difference (Vte) and pH of the luminal fluid were recorded using a double-barrelled voltage and ion-sensitive microelectrode. RESULTS: In control rats, the Vte was -40.7+/-2.4 mV and the tubular fluid pH was 6.44+/-0.07; in potassium-depleted animals, the Vte was -15.0+/-1.4 mV and the pH was 6.76+/-0.03. The pH values in both groups of animals were significantly lower than would be predicted from the Vte and systemic pH for passive H+ distribution, indicating active proton secretion. Moreover, in hypokalaemic rats, this difference from predicted pH was significantly greater than in control animals (control = 0.27+/-0.06 vs. low-potassium = 0.46+/-0.03; P<0.01), suggesting enhanced active proton secretion. During perfusion with a solution containing BaCl2, the late distal tubule Vte became lumen positive in potassium-depleted rats, contrasting with an increased lumen negativity in potassium-replete controls. The barium-induced lumen-positive potential difference observed in the hypokalaemic rats was abolished by intravenous administration of acetazolamide. CONCLUSION: These data are consistent with enhanced electrogenic proton secretion (H+ -ATPase) during dietary potassium deprivation.

Animals↗
PubMed1997

Enhancing endogenous effects of natriuretic peptides: inhibitors of neutral endopeptidase (EC.3.4.24.11) and phosphodiesterase.

Because diuretic drugs remain the main treatment for disorders of sodium and water metabolism, the quest for improved diuretic and natriuretic agents continues in the hope of achieving fewer side effects and a more rational basis in pathophysiology. One aim has been to enhance endogenous diuretic and natriuretic activity by selective manipulation of atrial natriuretic peptide and related compounds. The first approach has been to inhibit degradation of these peptides using inhibitors of their main catabolic enzyme, neutral endopeptidase, and to offset any antagonistic effect of the renin-angiotensin system by combination with an angiotensin-converting enzyme inhibitor. The second and more recent approach has been to inhibit breakdown of the second messenger of atrial natriuretic peptide, cGMP, using phosphodiesterase inhibitors. As yet, neutral endopeptidase inhibition has not advanced successfully beyond animal experimentation and phosphodiesterase inhibition is still in its infancy. Both strategies suffer from the problem that, on the one hand, neutral endopeptidase metabolizes a variety of bioactive peptides, including endothelin, and it is not possible to develop inhibitors that will be selective for a given peptide; whereas, on the other hand, there are several phosphodiesterase isoforms metabolizing cGMP and cAMP, both second messengers for many different bioactive compounds, and selective inhibitors are still under development.

Animals↗
PubMed1997

The effects of respiratory alkalosis and acidosis on net bicarbonate flux along the rat loop of Henle in vivo.

We have studied the effects of acute respiratory alkalosis (ARALK, hyperventilation) and acidosis (ARA, 8% CO2), chronic respiratory acidosis (CRA; 10% CO2 for 7-10 days), and subsequent recovery from CRA breathing air on loop of Henle (LOH) net bicarbonate flux (JHCO3) by in vivo tubule microperfusion in anesthetized rats. In ARALK blood, pH increased to 7.6, and blood bicarbonate concentration ([HCO3-]) decreased from 29 to 22 mM. Fractional urinary bicarbonate excretion (FEHCO3) increased threefold, but LOH JHCO3 was unchanged. In ARA, blood pH fell to 7.2, and blood [HCO3-] rose from 28 to 34 mM; FEHCO3 was reduced to < 0.1%, but LOH JHCO3 was unaltered. In CRA, blood pH fell to 7.2, and blood [HCO3-] increased to > 50 mM, whereas FEHCO3 decreased to < 0.1%. JHCO3 was reduced by approximately 30%. Bicarbonaturia occurred when CRA rats breathed air, yet LOH JHCO3 increased (by 30%) to normal. These results suggest that LOH JHCO3 is affected by the blood-to-tubule lumen [HCO3-] gradient and HCO3- backflux. When the usual perfusing solution at 20 nl/min was made HCO3- free, mean JHCO3 was -34.5 +/- 4.4 pmol/min compared with 210 +/- 28.1 pmol/min plus HCO3-. When a low-NaCl perfusate (to minimize net fluid absorption) containing mannitol and acetazolamide (2 x 10(-4) M, to abolish H(+)-dependent JHCO3) was used, JHCO3 was -112.8 +/- 5.6 pmol/min. Comparable values for JHCO3 at 10 nl/min were -35.9 +/- 5.8 and -72.5 +/- 8.8 pmol/min, respectively. These data indicate significant backflux of HCO3-along the LOH, which depends on the blood-to-lumen [HCO3-] gradient; in addition to any underlying changes in active acid-base transport mechanisms, HCO3- permeability and backflux are important determinants of LOH JHCO3 in vivo.

Acidosis, Respiratory↗
PubMed1996

Bladder epithelial oxygen tension--a new means of monitoring regional perfusion? Preliminary study in a model of exsanguination/fluid repletion.

OBJECTIVE: To assess whether monitoring of bladder epithelial oxygen tension (BEOT) would provide an indication of regional (renal) organ perfusion in an exsanguination/fluid repletion animal model. DESIGN: Prospective non-randomized laboratory study. SETTING: Research laboratory. INTERVENTIONS: Eight anaesthetised, spontaneously breathing Sprague-Dawley male rats weighing approximately 200 g were instrumented. They received 1-ml aliquots of fluid until no further haemodynamic improvement was seen, followed by removal of 1-ml aliquots of blood until renal blood flow fell by 50%. The animal was then resuscitated with repeated 1 to 2-ml aliquots of fluid until no further improvement was achieved and, finally, progressively exsanguinated to cardiovascular collapse. MEASUREMENTS AND RESULTS: A continuous Clark-type oxygen electrode lying in contact with the inside wall of the bladder measured changes in BEOT during these exsanguination and fluid repletion manoeuvres. Changes in BEOT closely mirrored both systemic (blood pressure and aortic blood flow) and regional (renal blood flow) haemodynamic changes. A direct correlation existed between percentage change in BEOT and base deficit, and an indirect correlation was seen with arterial oxygen tension. CONCLUSIONS: Measurement of BEOT may be a useful and relatively non-invasive means of monitoring regional organ perfusion. Further studies are warranted.

Animals↗
PubMed1996

Ambulatory blood pressure profiles and plasminogen activator inhibitor (PAI-1) activity in lean women with and without the polycystic ovary syndrome.

OBJECTIVE: Hyperinsulinaemic women with the polycystic ovary syndrome (PCOS) may be at increased risk of vascular disease later in life, mediated by blood pressure or lipid abnormalities or by elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1) activity. PAI-1 may also be involved in ovarian follicle development and ovarian connective tissue remodelling. We measured plasma PAI-1 activity and 24-hour ambulatory blood pressure records in women with and without PCOS. DESIGN: Cross-sectional study of three groups. PATIENTS: Twenty-four non-obese women with a classic ovarian ultrasound appearance of PCO and extreme menstrual disturbance (Group 1), 26 matched controls with a normal menstrual cycle and an ultrasound appearance of PCO (Group 2) and 10 matched controls with a normal menstrual cycle and normal ovarian ultrasound (Group 3). MEASUREMENTS: Twenty-four hour ambulatory blood pressure recordings (Spacelabs 90207), ovarian ultrasonography, fasting plasma insulin and glucose, plasma PAI-1 activity, HDL and total cholesterol, triglycerides, gonadotrophins and testosterone. Family history of premature vascular disease. RESULTS: Median fasting plasma insulin was significantly higher in Group 1 (45.8 pmol/l, range 12.9-161.9) than in Group 2 (28.1 pmol/l; range 13.6-91; P < 0.05) or Group 3 (26.0 pmol/l; range 13.5-63.3; P < 0.05). There were no differences between groups in 24-hour, daytime or night-time ambulatory blood pressure measurements, and no relation between plasma insulin and any blood pressure variable. Mean plasma PAI-1 activity was higher in Group 1 (10.0 +/- 7.1 AU/l) than in Group 2 (6.0 +/- 4.6 AU/l; P < 0.05) or Group 3 (5.1 +/- 3.5 AU/l; P = 0.06). There was a significant independent direct relation between fasting plasma insulin and PAI-activity (r = 0.41, R2 = 0.154; F1,59 = 11.38; P = 0.001). Groups did not differ in parental history of premature vascular disease, or in mean HDL or fasting triglyceride levels. CONCLUSIONS: The only measurable vascular risk factor associated with hyperinsulinaemia and menstrual disturbance in non-obese women with PCOS is an elevated plasma PAI-1 activity. These women did not differ from controls in ambulatory blood pressure profiles, lipid measurements or in a parental history of premature vascular disease. PAI-1 and plasminogen are involved in ovarian follicle maturation and the present finding suggests a biologically plausible link between hyperinsulinaemia, anovulation and vascular risk in PCOS.

Adult↗
PubMed1995

Bicarbonate transport along the loop of Henle effects of adrenal steroids.

The role of adrenal steroids in the regulation of bicarbonate absorption in the loop of Henle was studied by in vivo microperfusion. Bicarbonate transport (JHCO3) was measured by microcalorimetry and fluid reabsorption by [14C]inulin, 7-10 days after surgery, in 1) sham-operated control rats, 2) adrenalectomized (Adx) rats, 3) Adx rats receiving dexamethasone (1.2 micrograms.100 g body wt-1.24 h-1) and a low dose of aldosterone (0.5 micrograms.100 g body wt-1.24 h-1), 4) Adx rats receiving dexamethasone, 5) Adx rats receiving a low dose of aldosterone, and 6) Adx rats receiving a high dose of aldosterone (1.0 micrograms.100 g body wt-1.24 h-1). JHCO3 along the loop of Henle was decreased by 40% in Adx rats. JHCO3 was increased by dexamethasone alone and by dexamethasone plus a low dose of aldosterone to rates observed in fully supplemented Adx rats. Aldosterone given alone at a low physiological dose had no effect, but, when administered at a high dose, returned JHCO3 to normal.

Absorption↗
PubMed1994

The effect of acute metabolic alkalosis on bicarbonate transport along the loop of Henle. The role of active transport processes and passive paracellular backflux.

The loop of Henle (LOH) reabsorbs approximately 15% of filtered HCO3- via a luminal Na(+)-H+ exchanger and H+ATPase. During acute metabolic alkalosis (AMA) induced by i.v. HCO3- infusion, we have observed previously inhibition of LOH net HCO3- reabsorption (JHCO3-), which contributes to urinary elimination of the HCO3- load and correction of the systemic alkalosis. To determine whether the activities of the Na(+)-H+ exchanger and/or H(+)-ATPase are reduced during AMA, two inhibitors believed to be sufficiently specific for each transporter were delivered by in vivo LOH microperfusion during AMA. AMA reduced LOH JHCO3- from 205.0 +/- 10.8 to 96.2 +/- 11.8 pmol.min-1 (P < 0.001). Luminal perfusion with bafilomycin A1 (10(-4) mol.l-1) caused a further reduction in JHCO3- by 83% and ethylisopropylamiloride (EIPA; 5.10(-4) mol.l-1) completely abolished net HCO3- reabsorption. The combination of bafilomycin A1 and EIPA in the luminal perfusate was additive, resulting in net HCO3- secretion (-66.6 +/- 20.8 pmol.min-1; P < 0.001) and abolished net fluid reabsorption (from 5.0 +/- 0.6 during AMA to 0.2 +/- 1.1 nl.min-1; P < 0.001). To establish whether HCO3- secretion via luminal stilbene-sensitive transport mechanism participates in LOH adaptation to AMA, we added diisothiocyanato-2,2'-stilbenedisulphonate (DIDS; 10(-4) mol.l-1) to the perfusate. No effect was found.(ABSTRACT TRUNCATED AT 250 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Potassium and sodium transport along the loop of Henle: effects of altered dietary potassium intake.

We assessed the effects of changes in potassium (K+) balance on the function of the loop of Henle by a combination of renal clearance and microperfusion experiments. Rat superficial cortical nephrons were perfused in vivo at 20 nl.min-1 from late proximal to early distal tubule with an artificial end-proximal solution containing either 3.8 or 1.8 mM potassium. Rats were fed a control diet, a low-potassium diet for at least three weeks, or a high-potassium diet for 10 to 14 days. When compared with the appropriate end-proximal potassium concentration in the perfusion fluid, potassium absorption along the loop of Henle (JK) increased in potassium-depletion whereas sodium (JNa) and fluid (Jv) absorption decreased. In rats fed a high-potassium diet, absorption of potassium, sodium and fluid was depressed. We propose that changes of external potassium balance affect the transport of electrolytes and fluid along the loop of Henle in vivo by modulating the transport of potassium and sodium primarily in the thick ascending limb. Changes in potassium reabsorption may also be affected by alterations of potassium-recycling.

Animals↗
PubMed1994

Gene transfer into the rat renal glomerulus via a mesangial cell vector: site-specific delivery, in situ amplification, and sustained expression of an exogenous gene in vivo.

To evaluate the pathophysiological function of specific molecules in the renal glomerulus, selective, sustained, and modifiable expression of such molecules will be required. Towards achieving this end, we devised a gene transfer system using the glomerular mesangial cell as a vector for gene delivery. A reporter gene which encodes bacterial beta-galactosidase was introduced into cultured rat mesangial cells, and the stable transfectants were transferred into the rat kidney via the renal artery, leading to selective entrapment within the glomeruli. In the normal kidney, the reporter cells populated into 57 +/- 13% of glomeruli site specifically, and the expression of beta-galactosidase was sustained for 4 wk and declined thereafter. Within the glomerulus, some of the reporter cells remained in the glomerular capillaries, while others repopulated the mesangial area and, in part, extended their cytoplasmic processes toward the surrounding capillaries. When the cells were transferred into glomeruli subjected to transient mesangiolysis induced by monoclonal antibody 1-22-3, in situ expression of beta-galactosidase was amplified 7-12-fold, and the enhanced level of expression continued for up to 8 wk. The mesangial cell vector system thus achieves site-specific delivery of an exogenous gene into the glomerulus and is amenable to in situ amplification and sustained expression by preconditioning of the target site.

Animals↗
PubMed1994

Bicarbonate transport along the loop of Henle. II. Effects of acid-base, dietary, and neurohumoral determinants.

The loop of Henle contributes to renal acidification by reabsorbing about 15% of filtered bicarbonate. To study the effects on loop of Henle bicarbonate transport (JHCO3) of acid-base disturbances and of several factors known to modulate sodium transport, these in vivo microperfusion studies were carried out in rats during: (a) acute and chronic metabolic acidosis, (b) acute and chronic (hypokalemic) metabolic alkalosis, (c) a control sodium diet, (d) a high-sodium diet, (e) angiotensin II (AII) intravenous infusion, (f) simultaneously intravenous infusion of both AII and the AT1 receptor antagonist DuP 753, (g) acute ipsilateral mechanicochemical renal denervation. Acute and chronic metabolic acidosis increased JHCO3; acute metabolic alkalosis significantly reduced JHCO3, whereas chronic hypokalemic alkalosis did not alter JHCO3. Bicarbonate transport increased in animals on a high-sodium intake and following AII administration, and the latter was inhibited by the AII (AT1) receptor antagonist DuP 753; acute renal denervation lowered bicarbonate transport. These data indicate that bicarbonate reabsorption along the loop of Henle in vivo is closely linked to systemic acid-base status and to several factors known to modulate sodium transport.

Acid-Base Imbalance↗
PubMed1993

Renal and extrarenal sites of action of diuretics.

This paper provides (a) a survey of the basic tubule transport mechanisms of sodium and potassium ions along the nephron, (b) a comparison of the overall renal effects of two diuretic agents (torasemide and furosemide), as assessed by renal clearance techniques, (c) an analysis of the tubule sites of action of torasemide evaluated by free-flow micropuncture and microperfusion techniques, and (d) a brief evaluation of some extrarenal transport effects of loop diuretics.

Animals↗