Biomedical subjects

B L Jensen

Publications and source records attributed to B L Jensen.

At least 19 recordsLinked to original sources

PubMed2006

Intercellular calcium signaling and nitric oxide feedback during constriction of rabbit renal afferent arterioles.

Vasoconstriction and increase in the intracellular calcium concentration ([Ca(2+)](i)) of vascular smooth muscle cells may cause an increase of endothelial cell [Ca(2+)](i), which, in turn, augments nitric oxide (NO) production and inhibits smooth muscle cell contraction. This hypothesis was tested in microperfused rabbit renal afferent arterioles, using fluorescence imaging microscopy with the calcium-sensitive dye fura-2 and the NO-sensitive dye 4-amino-5-methylamino-2',7'-difluorescein. Both dyes were loaded into smooth muscle and endothelium. Depolarization with 100 mmol/l KCl led to a transient vasoconstriction which was converted into a sustained response by N-nitro-l-arginine methyl ester (l-NAME). Depolarization increased smooth muscle cell [Ca(2+)](i) from 162 +/- 15 nmol/l to a peak of 555 +/- 70 nmol/l (n = 7), and this response was inhibited by 80% by the l-type calcium channel blocker calciseptine. After a delay of 10 s, [Ca(2+)](i) increased in endothelial cells immediately adjacent to reactive smooth muscle cells, and this calcium wave spread in a nonregenerative fashion laterally into the endothelial cell layer with a velocity of 1.2 microm/s. Depolarization with 100 mmol/l KCl led to a significant increase in NO production ([NO](i)) which was inhibited by l-NAME (n = 5). Acetylcholine caused a rapid increase in endothelial [Ca(2+)](i), which did not transfer to the smooth muscle cells. l-NAME treatment did not affect changes in smooth muscle [Ca(2+)](i) after depolarization, but it did increase the calcium sensitivity of the contractile apparatus. We conclude that depolarization increases smooth muscle [Ca(2+)](i) which is transferred to the endothelial cells and stimulates NO production which curtails vasoconstriction by reducing the calcium sensitivity of the contractile apparatus.

Acetylcholine↗

PubMed2006

Cyclooxygenase type 2 is increased in obstructed rat and human ureter and contributes to pelvic pressure increase after obstruction.

Prostanoids exert physiological effects on ureteral contractility that may lead to pressure changes and pain during obstruction. In the present study, we examined whether (1) obstruction changes the expression of the two cyclooxygenase (COX) isoforms, COX-1 and COX-2 in human and rat ureters and (2) administration of a selective COX-2 inhibitor influences the pelvic pressure change after experimental ureteral obstruction. Rats were subjected to bilateral ureter obstruction. Ureters were removed and dissected into a proximal dilated and distal non-dilated segment. RNA and protein were extracted and analyzed for cyclooxygenase expression by quantitative polymerase chain reaction and Western blotting. Human ureter samples were obtained from patients undergoing radical nephrectomy. Rat and human ureteral samples were processed for immunohistochemistry. COX-1, but not COX-2 mRNA, was readily detected in the normal rat ureter. COX-2 mRNA and protein expression was increased in the proximal dilated ureter compared to distal non-dilated ureter. This increased COX-2 expression was associated with increased urinary prostaglandin E2 (PGE2) excretion after release of obstruction. Immunohistochemistry showed increased COX-2 labeling in surface epithelium and smooth muscle layers in both rat and human obstructed ureters compared to control ureters. Furthermore, contractile PGE2-EP1 and thromboxane TP receptors were expressed in ureteral smooth muscle. Systemic treatment with the COX-2 selective inhibitor parecoxib (5 mg/kg/day) attenuated the pelvic pressure increase during obstruction. In summary, COX-2 expression is significantly increased in the ureteral wall in response to obstruction in the rat and human ureter and COX-2 activity contributes to increased pelvic pressure after obstruction.

Animals↗

PubMed2005

Adrenomedullin expression during hypoxia in fetal sheep.

AIM: We asked how adrenomedullin (AM), a vasodilator peptide, was distributed in fetal sheep organs and whether expression of AM would be upregulated in response to moderate acute fetal hypoxia in vivo. METHODS: In four sheep at day 126-130 of gestation, nitrogen was added to the inspired air by tracheal infusion to reduce fetal arterial oxygen content for a period of 4 h. Control fetuses were from four ewes given a tracheal infusion of room air. Fetal and maternal blood samples were taken prior to and during hypoxia/sham hypoxia. Fetal tissue samples were frozen for RNA analysis and fixed for immunohistochemistry. RESULTS: In hypoxic fetuses, arterial oxygen content was significantly reduced to 50% compared with sham fetuses with no change in arterial pH in either group. Plasma ACTH levels rose significantly at 2 and 4 h in hypoxic fetuses only. Initial plasma concentrations of AM in control and hypoxic fetuses were 457 +/- 20 and 430 +/- 35 pg mL(-1) and did not change during the experiment. The relative abundance of AM mRNA was placental cotyledons >> lung > cerebral cortex approximately equal to renal cortex > left ventricle approximately equal to right ventricle > adrenal gland > renal medulla > aorta approximately equal to liver. Immunohistochemical staining for AM confirmed distinct labelling in organs with significant expression. AM mRNA level increased significantly in cerebral cortex of hypoxic fetuses. CONCLUSION: Our results show expression of AM in placenta and in several fetal organs in late gestation sheep. AM may participate in the cerebral vasodilatation that is an integral part of the fetal response to hypoxia.

Actins↗

PubMed2005

Reduced activity of 11beta-hydroxysteroid dehydrogenase type 2 is not responsible for sodium retention in nephrotic rats.

AIM: In mineralocorticoid target cells 11-beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) converts glucocorticoids into non-active metabolites thereby protecting the mineralocorticoid receptor (MR) from stimulation by glucocorticoids. In nephrotic syndrome, a decreased activity of 11betaHSD2 has been suggested to allow glucocorticoids to stimulate MR, thereby contributing to sodium retention. We tested this hypothesis in the puromycin aminonucleoside model of nephrotic syndrome in rats. METHODS: Complete sodium and potassium intakes and excretions (faeces and urine) were measured in rats in metabolic cages. RNase protection assay of mRNA and Western blotting of protein were used to estimate renocortical expression of 11betaHSD2 and of the MR downstream effector serum and glucocorticoid induced kinase (SGK). In an intervention series, dexamethasone was given [10 microg (100 g bw)(-1)] to suppress endogenous glucocorticoids in the proteinuric stage during active sodium retention. RESULTS: Nephrotic rats developed proteinuria, positive sodium balance, decreased plasma aldosterone concentration, and decreased urinary Na(+)/K(+) ratio. 11betaHSD2 mRNA expression was down-regulated but protein expression was unchanged. SGK mRNA and phosphorylated SGK protein were up-regulated while total SGK protein expression was unchanged. Dexamethasone treatment, which suppressed plasma corticosterone concentration, did not correct sodium balance or fluid retention in nephrotic rats. CONCLUSION: Our results do not support the hypothesis that stimulation of the MR by endogenous glucocorticoids induces sodium and fluid retention in experimental nephrotic syndrome in rats.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

PubMed2004

Membrane potential and cation channels in rat juxtaglomerular cells.

The relationship between membrane potential and cation channels in juxtaglomerular (JG) cells is not well understood. Here we review electrophysiological and molecular studies of JG cells demonstrating the presence of large voltage-sensitive, calcium-activated potassium channels (BK(Ca)) of the ZERO splice variant, which is also activated by cAMP. These channels explain the hyperpolarization, which has been observed after stimulation of renin release with cAMP. In addition, there is now evidence that JG cells express functional L-type voltage-dependent calcium channels (Ca(v) 1.2), which in situations with strong depolarization lead to calcium influx and inhibition of renin release. In most in vivo situations the membrane potential is probably protected against depolarization by the BK(Ca) channels.

Animals↗

PubMed2004

Rapid non-genomic effects of aldosterone on rodent vascular function.

The main role of aldosterone is to maintain body sodium homeostasis by promoting salt reabsorption in the collecting ducts of the kidney. In the cardiovascular system, aldosterone may be harmful in a number of disease states by inducing fibrosis and vascular dysfunction. The present review describes novel results from several laboratories, which show that aldosterone also has beneficial effects in the cardiovascular system by stimulating the production of nitric oxide (NO) from the endothelium. The effect of aldosterone is seen within minutes, and is not inhibited by blockers of gene transcription, thus pointing to a non-genomic mechanism. Furthermore, this potentially beneficial effect is observed at low physiological concentrations of aldosterone (0.1-10 pm). The effect is mediated by the classical mineralocorticoid receptor, and it involves heat shock protein 90, phosphatidylinositol (PI)-3 kinase, protein kinase B, endothelial nitric oxide synthase, and liberation of NO. It is proposed that in healthy individuals with a functioning NO system, the detrimental effects of aldosterone on cardiovascular function are balanced by activation of the potentially beneficial effect of NO. However, in situations with endothelial dysfunction, such as congestive heart failure and hypertension, the negative effects of aldosterone are unopposed and inhibition of aldosterone is warranted.

Aldosterone↗

PubMed2004

The renin-angiotensin system in kidney development: role of COX-2 and adrenal steroids.

Recent data from studies in rodents with targeted gene disruption and pharmacological antagonists have shown that the renin-angiotensin-aldosterone system (RAAS) and cyclooxygenase type-2 (COX-2) are necessary for late stages of kidney development. The present review summarizes data on the developmental changes of RAAS and COX-2 and the pathways by which they are activated; their possible interplay and the mechanisms by which they affect kidney development. Intrarenal and circulating renin and angiotensin II (ANG II) are stimulated at birth in most mammals. In rats, renin and ANG II stay significantly elevated in the suckling period while aldosterone stabilizes at an adult level. COX-2 is stimulated in thick ascending limb of Henle's loop in the suckling period at a time when urine concentrating ability is not developed. Data suggest that this induction is mediated by combined low plasma glucocorticoid concentration and by a low NaCl intake. Studies with selective inhibitors of COX-2 and COX-2 null mice show that COX-2 activity stimulates renin secretion from JG-cells during postnatal kidney development and that lack of COX-2 activity leads to pathological change in cortical architecture and eventually to renal failure. In the postnatal period, ANG II initiates and maintains pelvic and ureteric contractions necessary for urine flow. Lack of ANG II in the neonatal period is thought to cause injury by a chronic increase of renal pelvic pressure. Aldosterone is crucial for survival and growth in the neonatal period through its effects on sodium reabsorption and the intrarenal sensitivity to aldosterone is increased in the postnatal period. Final maturation of the kidney occurs through an intimate interplay between a low dietary sodium intake and a non-responsive HPA-axis which stimulates cortical COX-2 activity. COX-2 supports increased activity of the RAAS and may contribute to a low concentrating ability.

Animals↗

PubMed2004

Early craniofacial morphology and growth in children with bilateral complete cleft lip and palate.

PURPOSE: Analysis of craniofacial morphology and growth in children with bilateral complete cleft lip and palate (BCCLP), compared with a control group with unilateral incomplete cleft lip (UICL), before any treatment as well as 20 months after lip closure. MATERIAL: The children were drawn from a group representing all Danish children with cleft born 1976 to 1981. Sixty-four children were included in the study (19 BCCLP and 45 UICL). The ages were 2 and 22 months at examinations 1 and 2, respectively. METHOD: The method of investigation was infant cephalometry in three projections. The craniofacial morphology was analyzed using linear, angular, and area variables. Growth was defined as the displacement vector from the coordinate of the corresponding landmark in the x-ray at examination 1 to its coordinate at examination 2, corrected for x-ray magnification. The growth of an anatomical region in a patient was assessed by investigating the growth pattern formed by a collection of individual growth vectors in that region. RESULTS: The BCCLP group differed significantly from the UICL group. The most striking findings in BCCLP were an extremely protruding premaxilla; markedly increased posterior maxillary width; increased width of the nasal cavity; short maxilla with reduced posterior height; short mandible; bimaxillary retrognathia; severe reduction in the size of the pharyngeal airway; and a more vertical facial growth pattern. CONCLUSION: Our findings indicate that a facial type including a wide and posterior short maxilla, short mandible, and bimaxillary retrognathia might be a liability factor that increases the probability of developing cleft lip and palate.

Case-Control Studies↗

PubMed2003

Rapid inhibition of vasoconstriction in renal afferent arterioles by aldosterone.

Aldosterone has been suggested to elicit vessel contraction via a nongenomic mechanism. We tested this proposal in microdissected, perfused rabbit renal afferent arterioles. Aldosterone had no effect on internal diameter in concentrations from 10(-10) to 10(-5) mol/L, but aldosterone abolished the ability of 100 mmol/L KCl to induce vascular contraction. The inhibitory effect of aldosterone was observed from 1 pmol/L. The inhibitory effect was significant after 5 minutes and maximal after 20 minutes and was fully reversible. Actinomycin D (10(-6) mol/L) prolonged the effect of aldosterone. The effect was abolished by the mineralocorticoid receptor antagonist spironolactone (10(-7) mol/L) but not by the glucocorticoid receptor antagonist mifepristone (10(-6) mol/L). The K+-mediated increase of intracellular calcium concentration in afferent arterioles was not affected by aldosterone. Mineralocorticoid receptor was detected by reverse transcription-polymerase chain reaction and immunohistochemistry in rat renal vasculature and rabbit endothelial cells. Inhibition of phosphatidylinositol (PI)-3 kinase with LY 294002 (3x10(-6) mol/L) restored sensitivity to K+ in the presence of aldosterone, and afferent arterioles were immunopositive for PI-3 kinase subunit p110alpha. Inhibition of NO formation by L-NAME (10(-4) mol/L) or inhibition of soluble guanylyl cyclase with 1H-(1,2,4)Oxadiazolo[4,3-a]quinoxaline-1-one restored K+-induced vasoreactivity in the presence of aldosterone. Similar to aldosterone, the NO donor sodium nitroprusside inhibited K+-induced vascular contraction. Geldanamycin (10(-6) mol/L), an inhibitor of heat shock protein 90, abolished aldosterone-induced vasorelaxation. We conclude that aldosterone inhibits depolarization-induced vasoconstriction in renal afferent arterioles by a rapid nongenomic mechanism that is initiated by mineralocorticoid receptor activation and involves PI-3 kinase, protein kinase B, and heat shock protein 90-mediated stimulation of NO generation.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

PubMed2003

Early craniofacial morphology and growth in children with nonsyndromic Robin Sequence.

PURPOSE: Craniofacial morphology and growth comparisons in children with untreated nonsyndromic Robin Sequence (RS) and a control group with unilateral incomplete cleft lip (UICL) in which the lip was surgically closed at 2 months of age. MATERIAL: The 52 children (7 RS and 45 UICL) included in the study were drawn from a group representing all Danish cleft children born 1976 through 1981. The ages of the children were 2 and 22 months at the time of examination 1 and 2, respectively. METHOD: The method of investigation was three-projection cephalometry. Craniofacial morphology was analyzed by means of linear, angular, and area variables. Growth at a specific anatomical location in a patient was defined as the displacement vector from the coordinate of the corresponding landmark at examination 1 to its coordinate at examination 2. RESULTS: The most striking findings in the RS group were markedly increased posterior maxillary width, increased width of the nasal cavity, short maxilla with reduced posterior height, short mandible, bimaxillary retrognathia, and severe reduction in size of the pharyngeal airway. The amount of facial growth was similar in the two groups; however, a tendency toward a more vertical growth direction was observed in the RS group. CONCLUSION: Facial morphology in children with RS differed significantly from that of children with UICL at both 2 and 22 months of age. The magnitude of facial growth was similar in the two groups, whereas a tendency toward a more vertical facial growth direction was observed in the RS group.

Cephalometry↗

PubMed2003

Craniofacial morphology and growth comparisons in children with Robin Sequence, isolated cleft palate, and unilateral complete cleft lip and palate.

OBJECTIVE: Comparison of early craniofacial morphology and growth in children with nonsyndromic Robin Sequence (RS), isolated cleft palate (ICP), and unilateral complete cleft lip and palate (UCCLP). SUBJECTS: One hundred eight children with cleft: 7 with RS, 53 with ICP, and 48 with UCCLP were included in the study. The children were drawn from the group of all Danish children with cleft born 1976 through 1981. METHOD: Three-projection infant cephalometry. RESULTS: The craniofacial morphology in the RS, ICP, and UCCLP groups had some common characteristics: a wide maxilla with decreased length and posterior height, wide nasal cavity, short mandible, bimaxillary retrognathia, and reduced pharyngeal airway. The shortest mandible was found in RS followed by ICP and UCCLP; the pharyngeal airway was reduced in RS and ICP, compared with UCCLP; and the maxillary complex and nasal cavity were wider in UCCLP than in the other groups. The amount of facial growth in all three groups was similar; however, the direction was more vertical in UCCLP than in RS and ICP. CONCLUSION: Except for a shorter RS mandible, the facial morphology of infants with RS and ICP was similar, as was the amount of facial growth and the growth pattern. The differences in facial morphology can be ascribed to the difference in the primary anomaly. The amount of facial growth was similar in the three groups; however, the growth pattern showed a more vertical direction in UCCLP than in RS and ICP. It is hypothesized that the mandibular retrognathia in RS represents the outer end of that of the ICP distribution.

Analysis of Variance↗

PubMed2002

Adrenocorticotrophic hormone (ACTH) stimulation of sheep fetal adrenal cortex can occur without increased expression of ACTH receptor (ACTH-R) mRNA.

In the present study, it was hypothesized that the adrenocorticotrophin hormone receptor (ACTH-R) would be up-regulated in the adrenal gland of the sheep fetus following infusion of physiological amounts of ACTH, as shown for adrenal cortical cells in culture. In chronically catheterized sheep, an intravenous infusion of ACTH(1-24) was given to 6 fetuses for 24 h at a rate of 0.5 microg h(-1), starting on Day 126 or 127 of gestation (term approximately 147 days). Four control fetuses received an infusion of vehicle (saline). Total RNA was extracted from the fetal adrenal glands by the guanidinium thiocyanate method. Expression of specific mRNAs was determined by ribonuclease protection assay using cRNA probes directed against: ACTH-R; the steroid enzymes side-chain cleavage (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17apha-hydroxylase (P450c17) and 21beta-hydroxylase (P450c21); and beta-actin. Ratios of mRNA expression to beta-actin mRNA expression (arbitrary units) were calculated to correct for differences in RNA quality between samples. The concentration (mean +/- SEM) of immunoreactive cortisol in fetal plasma was greater after ACTH infusion than after vehicle infusion (47 +/- 3 v. 13 +/- 2 ng mL(-1) respectively; P<0.001). Adrenal expression of P450scc and P450c21 mRNA increased after ACTH infusion (P<0.05), whereas expression of P450c17 and 3beta-HSD mRNA was unchanged. There was no difference in ACTH-R mRNA expression between ACTH- and vehicle-infused fetuses (254 +/- 48 v. 305 +/- 76 arbitrary units respectively). It was concluded that ACTH is able to increase plasma cortisol concentrations in the sheep fetus by up-regulating cortisol synthesis in the adrenal gland, but that in vivo this does not require up-regulation of ACTH-R mRNA.

3-Hydroxysteroid Dehydrogenases↗

PubMed2002

Early craniofacial morphology and growth in children with unoperated isolated cleft palate.

OBJECTIVE: Analysis of craniofacial morphology and growth in children with untreated isolated cleft palate (ICP) (cleft of the secondary palate only) at 2 and 22 months of age and comparison of the morphology and growth to that of a control group with unilateral incomplete cleft lip (UICL). MATERIAL AND METHODS: A total of 98 cleft children (53 with ICP and 45 with UICL) drawn from a larger group representing all Danish children with cleft born in the period 1976 to 1981 were included in the study. Craniofacial morphology and growth were analyzed using three-projection infant cephalometry. RESULTS: The ICP group differed significantly from the UICL group. The most striking findings in the ICP group were: short maxilla; reduced posterior maxillary height; increased posterior maxillary width (in the 2-month-old); short mandible; reduced posterior height of the mandible; bimaxillary retrognathia; and reduced pharyngeal depth, height, and area. The facial growth pattern was fairly similar in the two groups except for a somewhat more vertical growth direction in the ICP group. CONCLUSION: The facial morphology in ICP children differs significantly from that of children with UICL of the same age. The differences in facial morphology can be ascribed to the difference in the primary anomaly in the ICP group. The facial growth pattern was fairly similar in the ICP and UICL group; however, a somewhat more vertical growth direction was observed in the ICP group.

Body Height↗

PubMed2001

Differential expression of T- and L-type voltage-dependent calcium channels in renal resistance vessels.

The distribution of voltage-dependent calcium channels in kidney pre- and postglomerular resistance vessels was determined at the molecular and functional levels. Reverse transcription-polymerase chain reaction analysis of microdissected rat preglomerular vessels and cultured smooth muscle cells showed coexpression of mRNAs for T-type subunits (Ca(V)3.1, Ca(V)3.2) and for an L-type subunit (Ca(V)1.2). The same expression pattern was observed in juxtamedullary efferent arterioles and outer medullary vasa recta. No calcium channel messages were detected in cortical efferent arterioles. Ca(V)1.2 protein was demonstrated by immunochemical labeling of rat preglomerular vasculature and juxtamedullary efferent arterioles and vasa recta. Cortical efferent arterioles were not immunopositive. Recordings of intracellular calcium concentration with digital fluorescence imaging microscopy showed a significant increase of calcium in response to K(+) (100 mmol/L) in isolated afferent arterioles (140+/-25%) and in juxtamedullary efferent arterioles (118+/-21%). These calcium responses were attenuated by the L-type antagonist calciseptine and by the T-type antagonist mibefradil. Intracellular calcium increased in response to K(+) in cortical efferent arterioles (21+/-9%). Mibefradil and nickel concentration dependently blocked K(+)-induced contraction of perfused rabbit afferent arterioles. Calciseptine blocked the contraction mediated by K(+) (EC(50) 8x10(-14)). S-(-)-Bay K 8644 had no effect on vascular diameter in the afferent arteriole. We conclude that voltage-dependent L- and T-type calcium channels are expressed and of functional significance in renal cortical preglomerular vessels, in juxtamedullary efferent arterioles, and in outer medullary vasa recta, but not in cortical efferent arterioles.

Animals↗

PubMed2001

Furosemide stimulates macula densa cyclooxygenase-2 expression in rats.

BACKGROUND: During a low salt intake, maintenance of renal blood flow and renin secretion depends on intact formation of prostaglandins. In the juxtaglomerular apparatus, the inducible isoform of cyclooxygenase, cyclooxygenase-2 (COX-2), is restricted to the macula densa and the cortical thick ascending limb of Henle (cTALH) cells, and is inversely regulated by dietary salt intake. This study aimed to elucidate whether the effect of NaCl on macula densa COX-2 expression is mediated by transepithelial transport of NaCl. METHODS: To this end, male Sprague-Dawley rats received subcutaneous infusions of the loop diuretic furosemide (12 mg/day) or were fed with the diuretic hydrochlorothiazide (30 mg/kg day) for seven days each. To compensate for their salt and water loss, the animals had free access to normal water and to salt water (0.9% NaCl, 0.1% KCl). COX-2 expression in kidney cortex was assessed by immunohistochemical staining and by semiquantitative ribonuclease protection assay for COX-2 mRNA. RESULTS: After six days of furosemide infusion to salt-substituted rats, there was no change of extracellular volume. Furosemide led to a fivefold and threefold increase of plasma renin activity and renocortical renin mRNA level, respectively. In parallel, there was a threefold increase of renocortical COX-2 abundance, while the COX-1 mRNA level remained unchanged. Moreover, the percentage of juxtaglomerular apparatuses immunopositive for COX-2 increased threefold in response to furosemide compared with vehicle-infused animals. Hydrochlorothiazide treatment increased plasma renin activity twofold but did not change kidney cortical renin mRNA, COX-2 mRNA, or COX-2 immunoreactivity. CONCLUSION: Our findings suggest that inhibition of salt transport in the loop of Henle, but not in the distal tubule, causes a selective stimulation of COX-2 expression in the macula densa region. This up-regulation may be of relevance for macula densa signaling, which links tubular salt transport rate with glomerular filtration rate and renin secretion.

Animals↗

PubMed2001

Orofacial pain, jaw function, and temporomandibular disorders in women with a history of juvenile chronic arthritis or persistent juvenile chronic arthritis.

OBJECTIVES: We sought to study the long-term outcome of juvenile chronic arthritis (JCA) in the temporomandibular joint (TMJ). STUDY DESIGN: Temporomandibular disorders, including TMJ involvement, were assessed in 42 women with pauciarticular or polyarticular JCA--on average 25.8 years from disease onset--and compared with those found in matched control subjects. Disease-related parameters associated with temporomandibular disorders were identified. RESULTS: The TMJ was involved in 66.7% of the patients, most severely in extended pauciarticular JCA. Temporomandibular disorders were more frequent in the patients than in the control subjects, especially in those with persistent disease. The TMJ involvement was positively correlated with disease duration and negatively correlated with jaw opening and occlusal support. Duration of active JCA and history of functional pain were identified as predictors of present TMJ involvement. CONCLUSION: In a long-term follow-up, TMJ involvement proved frequent in the studied patients and was associated with long disease duration and previous pain on jaw opening. The findings suggest that patients with JCA should undergo orofacial evaluation on a regular basis.

Adult↗

PubMed2001

Conducted vasoconstriction in rat mesenteric arterioles: role for dihydropyridine-insensitive Ca(2+) channels.

The aim of this study was to evaluate the role of voltage-operated Ca(2+) channels in the initiation and conduction of vasoconstrictor responses to local micropipette electrical stimulation of rat mesenteric arterioles (28 +/- 1 microm, n = 79) in vivo. Local and conducted (600 microm upstream from the pipette) vasoconstriction was not blocked by TTX (1 micromol/l, n = 5), nifedipine, or nimodipine (10 micromol/l, n = 9). Increasing the K(+) concentration of the superfusate to 75 mmol/l did not evoke vasoconstriction, but this depolarizing stimulus reversibly abolished vasoconstrictor responses to current stimulation (n = 7). Addition of the T-type Ca(2+) antagonist mibefradil (10 micromol/l, n = 6) to the superfusate reversibly blocked local and conducted vasoconstriction to current stimulation. With the use of RT-PCR techniques, it was demonstrated that rat mesenteric arterioles <40 microm do not express mRNA for L-type Ca(2+) channels (alpha(1C)-subunit), whereas mRNA coding for T-type subunits was found (alpha(1G)- and alpha(1H)-subunits). The data indicate that L-type Ca(2+) channels are absent from rat mesenteric arterioles (<40 microm). Rather, the vasoconstrictor responses appear to rely on other types of voltage-gated, dihydropyridine-insensitive Ca(2+) channels, possibly of the T-type.

Adrenergic alpha-Antagonists↗

PubMed2001

Acute upregulation of COX-2 by renal artery stenosis.

This study aimed to characterize the influence of acute renal artery stenosis on cyclooxygenase-2 (COX-2) and renin expression in the juxtaglomerular apparatus. For this purpose, male Sprague-Dawley rats received a left renal artery clip, and COX-2 mRNA, COX-2 immunoreactivity, plasma renin activity, and renin mRNA levels were determined. COX-2 mRNA and COX-2 immunoreactivity in the macula densa region in the clipped kidneys increased as early as 6 h after clipping and reached a maximal expression 1-2 days after clipping. Although values for plasma renin activity were elevated markedly at all time points examined, remaining renin mRNA levels were unchanged after 6 h and then increased to reach a maximum value 1-2 days after clipping. In the contralateral intact kidney, renin mRNA and COX-2 immunoreactivity decreased to approximately 50% of their normal values. To investigate a possible causal relationship between the changes of COX-2 and of renin expression, clipped rats were treated with the COX-2 blocker celecoxib (40 mg. kg(-1). day(-1)). This treatment, however, did not change renin mRNA either in the clipped or in the contralateral intact kidney. Our findings indicate that renal artery stenosis causes ipsilaterally an acute upregulation and contralaterally a downregulation of juxtaglomerular COX-2 expression. The lacking effect of celecoxib on renin gene expression does not support the concept of a direct mediator function of COX-2-derived prostaglandins in the control of renin expression during renal hypoperfusion.

Animals↗