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M Kammerl

Publications and source records attributed to M Kammerl.

11 recordsLinked to original sources
PubMed2002

Role of renal nerves in stimulation of renin, COX-2, and nNOS in rat renal cortex during salt deficiency.

We investigated a possible involvement of the sympathetic nervous system in the parallel increase of renin, cyclooxygenase-2 (COX-2), and neuronal nitric oxide synthase (nNOS) gene expression in the juxtaglomerular apparatus of rat kidneys induced by salt deficiency. Therefore, we determined the effects of renal denervation and the beta-adrenoreceptor antagonist metoprolol (50 mg/kg body wt po, twice a day) on renocortical expression of renin, COX-2, and nNOS in rats fed a low-salt (0.02% wt/wt) diet or treated for 1 wk with ramipril (10 mg/kg body wt) in combination with a low-salt diet. We found that a low-salt diet in combination with ramipril strongly increased renocortical mRNA levels of renin, COX-2, and nNOS 9-, 7-, and 2.5-fold, respectively. Treatment with metoprolol did not change basal expression of the three genes or induction of renin and COX-2 gene expression, while induction of nNOS expression was clearly attenuated. Similarly, unilateral renal denervation attenuated induction of nNOS expression but had no effect on all other parameters. These findings suggest that beta-adrenergic stimulation is not required for stimulation of renin and COX-2 gene expression in the juxtaglomerular apparatus during salt deficiency. However, beta-adrenoreceptor activity or renal nerve activity appears to be required for the full stimulation of nNOS expression by low salt intake or combined with angiotensin-converting enzyme inhibition.

Angiotensin-Converting Enzyme Inhibitors↗
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↗
PubMed2000

Cyclooxygenase 2 and neuronal nitric oxide synthase expression in the renal cortex are not interdependent in states of salt deficiency.

Neuronal nitric oxide synthase (nNOS) and cyclooxygenase-2 (COX-2) expression in the kidney are localized to the cortical thick ascending limb of the loop of Henle (cTALH), including the macula region, and increase after salt restriction. Because of the similar localization and regulation of nNOS and COX-2 expression, we have examined whether there is a functional interrelationship between the expression of the two enzymes. Male Sprague Dawley rats were fed for 1 week either a low-salt diet (0.02% w/w) which produced moderate increases of nNOS and COX-2 expression, or low salt combined with the angiotensin I converting enzyme inhibitor ramipril (10 mg/kg per day), which produced strong increases of renocortical nNOS and COX-2 expressions. To inhibit nNOS or COX-2 activities, animals received in addition N(G)-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg per day) or rofecoxib (10 mg/kg per day) for 1 week, respectively. L-NAME treatment did not change COX-2 expression and conversely rofecoxib treatment did not change nNOS expression in the kidney cortex under any experimental conditions. L-NAME but not rofecoxib attenuated renin mRNA levels. Rofecoxib markedly reduced renal prostanoid excretion. These findings suggest that under these conditions the control of nNOS and COX-2 gene expression in the macula densa regions of the kidney cortex are not dependent on each other.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Effects of chronic hypoxia on renal renin gene expression in rats.

BACKGROUND: The effects of hypoxia on renin secretion and renin gene expression have been controversial. In recent studies, we have demonstrated that acute hypoxia of 6 h duration caused a marked stimulation of renin secretion and renal renin gene expression. This hypoxia-induced stimulation of the renin-angiotensin system might contribute, for example, to the progression of chronic renal failure and to the development of hypertension in the sleep-apnoea syndrome. For this reason, we were interested in the more chronic effects of hypoxia on renal renin gene expression and its possible regulation. METHODS: Male rats were exposed to chronic normobaric hypoxia (10% O(2)) for 2 and 4 weeks. Additional groups of rats were treated with an endothelin ET(A) receptor antagonist, LU135252, or a NO donor, molsidomine, respectively. Systolic blood pressure and right ventricular pressures were measured. Renal renin, endothelin-1 and endothelin-3 gene expression were quantitated using RNAase protection assays. RESULTS: During chronic hypoxia, haematocrit increased to 72+/-2%, and right ventricular pressure increased by a mean of 26 mmHg. Renal renin gene expression was halved during 4 weeks of chronic hypoxia. This decrease was reversed by endothelin receptor blockade (105 or 140% of baseline values after treatment for weeks 3-4 or 1-4). Furthermore, there was a trend of increasing renal endothelin-1 gene expression (to 173% of baseline values) after 4 weeks of hypoxia. Systolic blood pressure increased moderately during 4 weeks of chronic hypoxia from 129+/-2 to 150+/-4 mmHg. This blood pressure increase was higher in rats treated for 4 weeks with an endothelin receptor antagonist (196+/-11 mmHg). CONCLUSIONS: Chronic hypoxia (in contrast to acute hypoxia) suppresses renal renin gene expression. This inhibition presumably is mediated by endothelins.

Animals↗
PubMed1996

Gallbladder motility in systemic sclerosis.

In 20 patients with systemic sclerosis (SSc) and 24 healthy controls, gallbladder motility was evaluated by abdominal ultrasonography after stimulation by a standard liquid meal. Results from patients with normal and disturbed oesophageal function were analysed separately in order to investigate the significance of gallbladder motility as a parameter for gastrointestinal involvement in SSc. All patients showed a marked decrease in gallbladder size after stimulation (patients 61 +/- 13%; controls 48 +/- 12%). Patients with oesophageal dysfunction (n = 12) had a slightly lower gallbladder contraction (maximal decrease = 58 +/- 13%) when compared to patients with normal oesophageal function (n = 8; 66 +/- 13%); however, this difference was not statistically significant. Gallbladder motility in patients with SSc was not reduced when compared with healthy controls. SSc-induced oesophageal dysfunction was not associated with impaired gallbladder motility. Thus, measurement of gallbladder emptying is not a helpful tool when looking for gastrointestinal involvement in SSc.

Adolescent↗
PubMed1976

[Incidence of autologous spermatozoa antibodies in a group of unselected andrologic patients].

Determination of autologous sperm antibodies in the serum of 278 male adults of an unselected andrological patient material is reported. Positive test results were found in 3 patients using the macroscopic agglutination test according to Kibrick (1.1%), in 21 patients using the microscopical agglutination test according to Franklin-Dukes (7.6%), in 2 patients using the immobilization test according to Isojima (0.7%) and in 1 patient using the indirect immunofluorescence technique according to Coons and Kaplan (0.4%). Comparing the macroscopic and microscopic agglutination test a high degree of unspecific agglutinations were found in the latter excluding the microscopical agglutination test for the determination of antibodies. The relatively rare occurrence of autologous sperm antibodies in an unselected andrological patient material points to the fact that immunological methods seem to play no significant role in the diagnosis of male subfertility.

Antibody Formation↗
PubMedDate not supplied

SDF-1 expression is elevated in chronic human renal allograft rejection.

The exact mechanism of acute and chronic allograft rejection still remains unclear. The chemokine SDF-1 as mediator of allograft rejection has been under intensive investigation in liver, cardiac and bone marrow transplantation, whereas in renal transplantation, there are no reports about SDF-1 to date. This study was performed to evaluate if SDF-1 might also play an important role in human renal graft biopsies. One hundred and ninety formalin-fixed, paraffin-embedded renal allograft biopsies were included in the analysis from patients with normal renal graft morphology (according to Banff 97 classification grade 1, n = 84), with acute interstitial rejection (Banff grade 4 type I, n = 10), with acute vascular rejection (Banff grade 4 type II, n = 21), with chronic allograft nephropathy (CAN, Banff grade 5, n = 23), and without rejection but with various other lesions (Banff grade 6, n = 42). SDF-1 was localized by immunohistochemistry. In biopsies with CAN, SDF-1 expression was significantly elevated in interstitial infiltrates and infiltrating neointimal cells of arteries compared with biopsies with normal renal graft morphology. This is the first study describing a role of SDF-1 in human renal allograft rejection. We were able to demonstrate in a large number of biopsies an upregulation of SDF-1 in patients with CAN. Whether SDF-1 has pro-inflammatory or protective properties in this setting has to be evaluated in further trials.

Biomarkers↗