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Biomedical subjects

M Lebel

Publications and source records attributed to M Lebel.

At least 55 records · Page 3Linked to original sources
PubMed1996

Eicosanoid modulation of the norepinephrine effect on blood pressure and renal hemodynamics in humans.

The main objective of this study was to investigate the role of eicosanoids in modulating the effect of norepinephrine (NE) on blood pressure and renal hemodynamics during NE administration. Eight healthy volunteers were randomly assigned to three (1 week apart) infusion periods (180 min) with either dextrose 5% or NE, with or without indomethacin pretreatment. Pressor doses of NE induced marked alterations in renal hemodynamics and concomitant increases in eicosanoid excretion rates. The production of the vasodilatory prostacyclin (PGI2), as reflected in the excretion rate of the stable metabolites 6-keto-prostaglandin (PG)F1(alpha) and 2,3-dinor-6-keto-PGF1(alpha), was 2.7 times higher than that of the constrictor thromboxane (TX)A2, which was measured as the stable derivative TXB2. Indomethacin pretreatment blunted the NE-induced augmentation in eicosanoid excretion and resulted in further increases in arterial pressure and in renal vascular resistance. These results demonstrate that PGI2 attenuates the systemic and the renal hemodynamic vasoconstrictor effect of NE in normotensive control normal subjects.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Renal hemodynamics during norepinephrine and low-dose dopamine infusions in man.

OBJECTIVE: To characterize the effects of pressor doses of norepinephrine and low-dose dopamine (3 micrograms/kg/min) on renal hemodynamics in man, as well as to determine the clinical relevance of combining dopamine with norepinephrine. DESIGN: Prospective, single-blind, randomized study. SETTING: Clinical research unit of a tertiary care hospital. SUBJECTS. Six healthy male volunteers ranging in age between 20 and 28 yrs. INTERVENTIONS: The subjects were assigned randomly to four treatments (1 wk apart) in which renal hemodynamics and electrolyte excretion were assessed. Treatments consisted of 180-min infusions of the following: a) 0.9% sodium chloride (control); b) pressor doses of norepinephrine; c) dopamine at 3 micrograms/kg/min; and d) pressor doses of norepinephrine and dopamine at 3 micrograms/kg/min. Pressor doses of norepinephrine was defined as doses required to increase mean arterial pressure (MAP) by 20 mm Hg. MEASUREMENTS AND MAIN RESULTS: Glomerular filtration rate and renal blood flow were derived from inulin and para-aminohippurate clearances, respectively. Urine output and urine solute excretion were also determined. The mean norepinephrine dose required to increase MAP by 22 +/- 2 mm Hg was 118 +/- 30 ng/kg/min (range 76 to 164). After the addition of dopamine, similar doses of norepinephrine resulted in an MAP increase of 15 +/- 4 mm Hg. Glomerular filtration rate and urine output were comparable under all conditions. The infusion of norepinephrine decreased renal blood flow from 1241 +/- 208 to 922 +/- 143 mL/min/1.73 m2 (p = .03). The addition of dopamine returned renal blood flow to baseline values. The clearance of urine sodium increased significantly with the infusion of dopamine alone (p = .03). All subjects completed the four treatment periods. Adverse events, manifested mostly as palpitations and flushing, were rare and self-limiting. CONCLUSIONS: The addition of dopamine (3 micrograms/kg/min) to pressor doses of norepinephrine normalized renal blood flow in healthy volunteers. These hemodynamic changes were not reflected in urine output and glomerular filtration rate; hence, these monitoring parameters may be unreliable indicators of renal function in the setting of vasopressor therapy. In addition, systemic effects were observed with dopamine (3 micrograms/kg/min), as indicated by a decrease in MAP.

Adult↗
PubMed1996

Prostaglandins and renal function in hypertensive patients with unilateral renal artery stenosis and patients with essential hypertension.

OBJECTIVE: This study was designed to compare the effects of prostaglandin synthesis inhibition on calculated preglomerular and postglomerular resistance in hypertensive patients with unilateral renal artery stenosis (RAS) and in patients with essential hypertension. DESIGN AND METHODS: Sixteen patients with suspected renovascular hypertension underwent renal angiography: eight had unilateral renal artery stenosis > or = 70% and eight had normal angiograms or stenosis < or = 40%. Radionuclide renography and 6 h urinary collection were performed twice for each subject, at baseline and after indomethacin administration. Levels of urinary vasodilatory prostaglandins were measured by specific radioimmunoassays. Visual image analysis was performed to determine the parenchymal transit time (PTT). The glomerular filtration rate (GFR) was calculated from the plasma clearance of [99mTc]-diethylenetriamine pentaacetic acid (DTPA). The preglomerular and postglomerular resistances were estimated according to Gomez's equations. RESULTS: The prostaglandin excretion decreased significantly after indomethacin administration both in RAS and in essential hypertension patients. The PTT increased from 230 +/- 10 to 340 +/- 40s in the stenotic kidney compared with the contralateral kidney and the kidneys of essential hypertension patients. The GFR was decreased both in stenotic and in contralateral kidneys (48 +/- 4 to 37 +/- 5 and 60 +/- 4 to 52 +/- 5 ml/min, respectively) but did not decline in the kidneys of essential hypertension patients. The preglomerular resistance increased both in stenotic and in contralateral kidneys, whereas it did not rise significantly in the kidneys of essential hypertension patients. The postglomerular resistance in stenotic and contralateral kidneys of RAS patients was not altered. CONCLUSIONS: Prostaglandins limit GFR decreases in RAS by preventing preglomerular constriction without interfering with postglomerular constriction. Thus, the action of vasoactive prostaglandins on preglomerular resistance might maintain renal function in the short term by limiting the fall in GFR in the stenotic kidney and by increasing the GFR in the contralateral kidney.

Blood Pressure↗
PubMed1995

Effect of recombinant human erythropoietin therapy on ambulatory blood pressure in normotensive and in untreated borderline hypertensive hemodialysis patients.

The effect of recombinant human erythropoietin (r-HuEPO) on ambulatory blood pressure (ABP) was studied in 13 anemic hemodialysis patients. Eight patients were normotensive and five patients had untreated borderline systolic hypertension. Mean hemoglobin increased from 82 +/- 3 g/L to 114 +/- 3 g/L (P < .01) after 3 to 4 months of r-HuEPO therapy (30 to 40 U/kg) administered subcutaneously three times weekly. Mean 24-h systolic and diastolic ABP measurements were significantly increased by 16 +/- 4 mm Hg and 10 +/- 2 mm Hg, respectively (P < .01 for both). Blood pressure was increased in all but one patient. In six patients, the mean 24-h systolic and diastolic ABP measurements were more than 160 mm Hg or 90 mm Hg at the end of the study. The increase in ABP was slightly but not significantly greater during the waking period as compared with the sleeping period and the circadian blood pressure pattern was not modified by r-HuEPO treatment. The blood pressure load (percentage of ABP reading exceeding 140/90 mm Hg during the waking period and 120/90 mm Hg during the sleeping period) was significantly increased (P < .05) after r-HuEPO therapy. Nine of the 13 patients failed to show the expected reduction in blood pressure during the sleeping period and were defined as "nondippers"; the others were defined as "dippers." During r-HuEPO therapy, the increase in ABP was similar in both dippers and nondippers. This suggests that the nondipper condition is not a risk factor for the development of hypertension during r-HuEPO therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Transgenic mice bearing the polyomavirus large T antigen directed by 2.1 kb of the keratin 19 promoter develop bronchiolar papillary tumors with progression to lung adenocarcinomas.

Keratin 19 is an intermediate filament protein produced by cells of simple epithelia and basal cells of stratified epithelia of different organs. These cell types are associated with important human cancers. We have used the keratin 19 promoter to target the expression of the polyomavirus (Py) large T-antigen, an immortalizing oncogene known to bind to the tumor suppressor retinoblastoma gene product, to epithelial cells. Individuals of the transgenic mouse line K19PyLT-6 developed one or two nodules in one of their lungs. By histology, the nodules were papillary tumors that consisted of nonciliated epithelial cells of the terminal bronchioles. In addition, infiltrates emanating from the nodules were consistent with the development of pulmonary adenocarcinomas. In situ hybridization techniques demonstrated large T-antigen expression in the tumors. Primary cultures were established from a lung tumor dissected from a K19PyLT-6 transgenic mouse. These large T-antigen-expressing cell lines produced the keratin proteins reminiscent of the epithelial origin of the lung tumor. However, further molecular studies indicated that these cell lines did not express Clara cells or pneumocytes markers. s.c. injection of the cell lines into nontransgenic syngeneic mice produced tumors in 2 weeks that resembled malignant pulmonary adenocarcinomas. These animals, which display tumor progression in situ, and the cell lines derived thereof provide a useful system for the study of lung tumorigenesis.

Adenocarcinoma↗
PubMed1994

Establishment and characterization of testicular cell lines from MT-PVLT-10 transgenic mice.

Males of the MT-PVLT-10 transgenic mouse line, which expresses the polyomavirus large T-antigen under the control of the metallothionein promoter, develop testicular adenomas and display seminal vesicle enlargement. Histological analysis of adenomatous testis indicates a predominance of Leydig cells, with few normal Sertoli cells or seminiferous tubules remaining. Primary cell cultures established from the testes of control nontransgenic animals (all ages) and young MT-PVLT-10 animals (before the appearance of any phenotype) quickly entered crisis and died. In contrast, permanent cell lines could be derived from pre- and postadenomatous testes from older MT-PVLT-10 mice. All primary cultures and cell lines expressed large T-antigen. A primary culture (D-37) derived from an MT-PVLT-10 male with normal testes but enlarged seminal vesicles has been maintained for over 2 years and experiments indicate that the D-37 culture is unable to form tumors in nude mice. In contrast, a primary culture (D-4) derived from adenomatous testes of an MT-PVLT-10 mouse is also immortal, but injection of this culture into nude mice consistently resulted in tumor formation. Cloning of the D-4 culture resulted in pure Sertoli or Leydig cell clones, neither of which could form tumor upon injection into nude mice. Injection of a mixture of both cell types did result in tumor formation, suggesting a dynamic interaction between these cell types in MT-PVLT-10-induced tumorigenesis.

Animals↗
PubMed1994

Sequence analysis of a novel cDNA which is overexpressed in testicular tumors from polyomavirus large T-antigen transgenic mice.

MT-PVLT-10 transgenic mice express the large T-antigen of polyomavirus under the control of the mouse metallothionein-1 promoter. The males of this transgenic line developed testicular tumor and seminal vesicle engorgement at advanced ages. A novel partial cDNA was identified which hybridized to a 2.6 kilobase mRNA. The expression of this mRNA increased approximately two- to fifteen-fold in immortalized cell lines derived from testicular tumors as compared to similar cell lines derived from pre-adenomatous testes. The in vivo pattern of expression for this cDNA as well as its expression in various primary cultures and established cell lines derived from testis of MT-PVLT-10 mice is presented. Overlapping cDNA clones from liver, testes, and brain cDNA libraries containing the entire coding region for this novel cDNA have been isolated and sequenced. The coding region of this gene comprises 1179 nucleotides and predicts a polypeptide of 393 amino acids (calculated molecular mass 44,318). Motif analysis of the amino acid sequence has revealed that it contains several hydrophobic alpha-helices characteristic of transmembrane proteins.

3T3 Cells↗
PubMed1994

Plasma endothelin levels and blood pressure in hemodialysis and in CAPD patients. Effect of subcutaneous erythropoietin replacement therapy.

We investigated plasma endothelin (ET) concentration and blood pressure in 44 patients with end stage renal failure chronically treated with either hemodialysis (n = 24) or continuous ambulatory peritoneal dialysis (CAPD) (n = 20). Half of the subjects were on chronic erythropoietin (r-HuEPO) replacement therapy (30-60 U/kg) subcutaneously, 3 times weekly. The mean plasma ET level of the whole group was about five fold higher than the normal range. Plasma ET concentration and mean blood pressure were higher in hemodialysis than in CAPD patients (33.3 +/- 2.1 vs 24.8 +/- 1.2 pg/ml, p < 0.01, and 101 +/- 2.4 vs 91 +/- 3 mmHg, p < 0.025). There was a significant correlation between plasma ET levels and systolic blood pressures in both groups (r = 0.45, p < 0.05). Patients (hemodialysis and CAPD) receiving subcutaneous r-HuEPO had higher mean blood pressure (99 +/- 3 vs 85 +/- 4 mmHg, p < 0.01), while their plasma ET levels were similar to untreated patients independent of the dialysis mode. However, a statistically significant correlation between plasma ET and systolic blood pressure was present only in the r-HuEPO treated group (r = 0.46, p < 0.05 vs r = 0.29, N.S., for the untreated group). These results show that plasma ET levels are markedly increased on both dialysis mode, but the values are lower in CAPD patients. Plasma ET concentrations significantly correlated with systolic blood pressures in the whole group of patients, and also in those receiving r-HuEPO replacement therapy.

Adult↗
PubMed1992

EMLA partially relieves the pain of EMG needling.

The aim of this study was to evaluate the efficacy of the topical analgesic cream EMLA in alleviating the pains caused by needling in electromyography (EMG). During the course of regular neurophysiology clinics, 34 Caucasian patients of both sexes, aged 21 to 69 yr (mean 38.5 +/- 11.4 SD), scheduled for electromyography, were studied. The EMLA was spread thickly on two EMG sites on each arm: E site, on the lateral dorsal aspect of the forearm and A site, on the thenar eminence. Randomization was pre-established. Whenever EMLA was applied blindly on one of the sites of the arm, the placebo was applied on the homologous site of the other arm. After at least 45 min of application (range 45-145 min, mean = 72.3 +/- 22.2), the needle was inserted into the skin and into the muscle. Then the electromyographist asked the patient to score his degree of pain on a visual analogue scale (VAS 1-10 cm) for each level of insertion. The results showed that on the skin of E site, the pain was less after EMLA than placebo (VAS = 0.75 +/- 1.36 vs 3.10 +/- 1.75, P = 0.0001). The untreated E site (placebo) was less sensitive than the untreated A site (VAS = 3.10 +/- 1.75 vs 6.09 +/- 1.96, P = 0.0001). Muscle insertion on E site was less painful on the EMLA sites than placebo (VAS = 2.83 +/- 2.45 vs 5.73 +/- 2.30, P = 0.0001). The VAS scores for skin and muscle insertion on A site were identical whether EMLA or placebo had been applied.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1992

Endocrine sodium and volume regulation in familial hyperkalemia with hypertension.

The hormonal regulation of sodium and volume homeostasis was investigated in three patients (two related) with the syndrome of familial hyperkalemic acidosis and hypertension with normal glomerular filtration rate. Recumbent plasma renin activity was low during normal sodium intake (135 mmol daily), and the response to upright posture or to low sodium diet (10 mmol daily) was blunted. Recumbent plasma aldosterone levels were normal in two patients and high in one, and the standing values were elevated in one; responses to upright posture were brisk on low sodium diet. Angiotensin II infusion induced a marked increase in plasma aldosterone. Plasma atrial natriuretic peptide was at the upper limit of normal during normal sodium intake, decreased during diuretic therapy, and increased during sodium chloride infusion in one patient. Basal urinary prostaglandin E2, prostaglandin F2 alpha, and 6-ketoprostaglandin F1 alpha excretion rates were decreased, and thromboxane B2 was increased. Total blood and plasma volumes were subnormal, whereas extracellular fluid volume and exchangeable sodium values were close to or above (in one patient) the mean normal values. Chronic treatment with hydrochlorothiazide in two patients corrected the hyperkalemic acidosis and hypertension, but on its discontinuation (in one patient) all biochemical abnormalities promptly reappeared.

Adult↗
PubMed1991

Effect of short-term administration of cromakalim on renal hemodynamics and eicosanoid excretion in essential hypertension.

Cromakalim, a novel potassium channel-activating drug, was administered for a 3-day period in eight untreated hospitalized patients with established hypertension. The fixed and single dose of 1.5 mg/day produced a significant reduction in systolic and diastolic blood pressure with a small increase in heart rate. Glomerular filtration rate was unchanged and effective renal plasma flow was slightly increased with a concomitant small decrease in filtration fraction and in renal vascular resistance. No significant change was observed in urinary prostaglandin (PG)E2, PGF2 alpha, and thromboxane B2, while 6-keto-PGF1 alpha (the stable metabolite of prostacyclin) rose from 189 +/- 6 to 368 +/- 115 ng/day. The renal excretion of 6-keto-PGF1 alpha correlates with the modification observed in renal plasma flow, suggesting a compensatory role for prostacylin in preserving renal hemodynamics during antihypertensive therapy with cromakalim.

Adult↗
PubMed1991

Arachidonic acid does not share the antihypertensive properties of linoleic acid and fish oil omega-3 fatty acids in a model of angiotensin II-induced hypertension in the rat.

Linoleic acid and fish oil omega-3 fatty acids, but not arachidonic acid, exerted antihypertensive effects in a model of angiotensin II-induced hypertension in rats. Indomethacin did not influence the systolic arterial pressure of arachidonic acid-treated hypertensive rats whereas compound L-641,953, a prostaglandin H2/thromboxane A2 receptor antagonist, caused a notable but statistically nonsignificant decrease in blood pressure in these animals. Although these results do not exclude entirely the possibility that the lack of antihypertensive effect of arachidonic acid may be due, in part, to the concomitant formation of vasoconstrictor prostanoids, they do not support it. These observations, as well as those of a previous study, indicate that linoleic acid and fish oil omega-3 fatty acids exert antihypertensive effects of their own, independently of the prostanoid system, and that these properties are not shared by arachidonic acid.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Renal eicosanoids and renal hemodynamics in early borderline hypertension.

To study the modulatory role of renal eicosanoids on renal hemodynamics and electrolyte excretion, pressor doses of norepinephrine (NE) were infused in 10 control subjects (mean age, 26 y) and 13 patients (mean age, 25 y) with borderline hypertension. The highest NE dose used (150 ng/kg/min) produced comparable increases in mean blood pressure in control subjects (20 +/- 2 mmHg) and in patients (23 +/- 3 mmHg). NE induced a significant increase in renal vascular resistance (p less than 0.01, both groups), with a smaller decrease in glomerular filtration rate resulting in a concomitant increase in filtration fraction (p less than 0.01, both groups). The renal hemodynamic changes tended to be more pronounced in borderline hypertension. NE infusion led to similar decreases in electrolyte clearances in the two groups. Urinary prostaglandin (PG)E2, PGF2 alpha (p less than 0.01), and 6-keto-PGF1 alpha increased with NE infusion. Urinary thromboxane (TX)B2 increased slightly in control subjects and decreased in borderline hypertension (p less than 0.05). The 6-keto-PGF1 alpha/TXB2 ratio, an index of vasodilation, was significantly increased (p less than 0.05) in borderline hypertension. These results demonstrate that in both groups pressor infusion of NE induced significant modifications in renal hemodynamics and in urinary electrolyte and eicosanoid excretion. The vasodilatory component of the renal eicosanoid system appears hyperresponsive in borderline hypertension, which may represent an early antihypertensive defense mechanism.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Effect of captopril injection in patients with moderate to severe hypertension.

The effect of intravenous captopril was studied in 24 white patients who had moderate to severe hypertension. Patients received incremental doses of 1 to 10 mg delivered at 10 min intervals over 50 to 80 min. Blood pressure (BP) was lowered within 5 to 10 min after the initial dose was administered and continued to decline, reaching a maximum response after 20 min (2 to 4 mg). At this time group mean BP fell from 175 +/- 3/111 +/- 1 to 166 +/- 3/97 +/- 2 mm Hg (P less than 0.01). Additional dose increments to an average cumulative dose of 40 mg did not increase the initial effect. No adverse side effects or symptomatic hypotension occurred in any subject. There was a significant correlation between diastolic BP decreases observed in response to intravenous captopril and subsequent long-term oral captopril therapy. The addition of hydrochlorothiazide increased the proportion of patients reaching normotension. We conclude that small intravenous bolus injections of captopril appear to be effective rapidly and are well tolerated in moderate to severe essential hypertension. Short-term intravenous administration seems to predict the response to chronic oral captopril therapy.

Administration, Oral↗
PubMed1990

Prostanoids and aldosterone-induced mild experimental hypertension in rats.

The goal of this study was to determine the role of prostanoids in a new model of mineralocorticoid-dependent hypertension induced by the subcutaneous infusion of aldosterone (1 micrograms/hr) to normal male Sprague-Dawley rats. This regimen caused a mild and gradual increase in systolic pressure over a period of 4 weeks (113 +/- 1 vs. 137 +/- 3 mm Hg) and was associated with an increase in the in vivo formation of prostaglandins I2 and E2 and of thromboxane A2 in the kidney. High sodium intake induced a fall in the urinary levels of prostaglandin E2 and a rise in the arterial pressure of control rats (126 +/- 1 vs. 113 +/- 1 mm Hg) but did not influence aldosterone-induced hypertension. Indomethacin (3.0 mg/kg/day) caused a profound inhibition of the in vivo synthesis of prostaglandin I2 and thromboxane A2 without modifying the renal production of prostaglandin E2. Although indomethacin exerted no effect on aldosterone-induced hypertension in rats fed a normal diet, it caused a further rise in systolic pressure in aldosterone-treated rats fed a high sodium diet (157 +/- 6 vs. 140 +/- 4 mm Hg). The results of this study in a model of aldosterone-induced mild hypertension in the rat indicate that 1) aldosterone exerts a stimulatory effect on the renal synthesis of prostanoid, particularly prostaglandin E2; 2) thromboxane A2 and prostaglandin I2 do not seem to play a role in aldosterone-induced hypertension under conditions of normal dietary salt intake, whereas the role of prostaglandin E2 is unclear; 3) there is enough sodium in a normal diet to allow for the maximal expression of the hypertensive effect of aldosterone; 4) prostaglandin I2 seems to play a significant role in modulating the cardiovascular impact of a high sodium diet in aldosterone-treated rats; and 5) the renal biosynthesis of prostaglandin E2 is particularly resistant to the inhibitory effect of indomethacin in vivo.

6-Ketoprostaglandin F1 alpha↗