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H H Schmidt

Publications and source records attributed to H H Schmidt.

At least 127 records · Page 7Linked to original sources
PubMed1994

Immunocytochemical localization of distinct isoforms of nitric oxide synthase in the juxtaglomerular apparatus of normal rat kidney.

Nitric oxide (NO) is a messenger molecule that functions as a vasodilator and accounts for the biologic activity of endothelium-derived relaxing factor (EDRF). The enzyme responsible for NO production, NO synthase (NOS), exists in different isoforms. Some are expressed constitutively in various tissues, whereas others require induction by endotoxin and cytokines. There is evidence that NO plays an important role in the regulation of basal renal vascular resistance and in the tubuloglomerular feedback response. Specific antibodies to a constitutive NOS isolated from rat brain (B-NOS) and an inducible NOS isolated from rat aortic smooth muscle (VSM-NOS) were used to establish the cellular and subcellular distribution of NOS in the kidney. Kidneys from normal rats were preserved and processed for light and electron microscopic immunohistochemical studies using both a preembedding and a postembedding horseradish peroxidase technique. By light microscopy, strong immunostaining for B-NOS was observed in the juxtaglomerular apparatus, where it was located in cells of the macula densa. In contrast, immunostaining for VSM-NOS was specifically located in the terminal afferent arteriole and occasionally also in the initial efferent arteriole in the juxtaglomerular apparatus. In addition, faint immunostaining was present in the entire distal tubule. There was no labeling of arcuate or interlobular arteries. The injection of lipopolysaccharide was associated with increased immunostaining for VSM-NOS in the afferent arteriole but had no effect on B-NOS staining. By electron microscopy, B-NOS immunostaining was present throughout the cytoplasm of the macula densa cells, where it appeared to be associated mainly with small vesicles. Immunostaining for VSM-NOS in the afferent arteriole exhibited a patchy distribution in some cells, whereas other cells were stained throughout the cytoplasm. These results indicate that two distinct isoforms of NOS are present in the juxtaglomerular apparatus and support the hypothesis that NOS is involved in the regulation of tubuloglomerular feedback and glomerular capillary pressure.

Amino Acid Oxidoreductases↗
PubMed1993

Neurons in rat cerebral cortex that synthesize nitric oxide: NADPH diaphorase histochemistry, NOS immunocytochemistry, and colocalization with GABA.

Neurons that stain for NADPH diaphorase, which colocalizes with nitric oxide synthase (NOS), are scattered uniformly across neocortex, and denser in entorhinal cortex. In the primary sensorimotor cortex, 0.5-2% of neurons contain NOS. These are most numerous in layers II-III, whereas NOS-positive fibers are concentrated in layers IV and VI. Most stained neurons are aspiny bipolar cells. Some in deep layers are multipolar; very few are pyramidal-shaped. In layer IV, NOS-positive neurons and their dendrites are confined to the septa between barrels. Retrograde tracing experiments demonstrate that NOS-positive cells are local circuit neurons. Double staining demonstrates that NOS-positive neurons also contain GABA.

Amino Acid Oxidoreductases↗
PubMed1993

Neurons in rat hippocampus that synthesize nitric oxide.

We studied the distribution and light- and electron-microscopic morphology of neurons in the hippocampal formation containing nitric oxide synthase (NOS), and thus likely to release nitric oxide, a freely diffusible neuromediator implicated in long-term potentiation. Only a small fraction of hippocampal neurons contained NOS or its marker, NADPH diaphorase. Most of the positive neurons were in the pyramidal layer of the subiculum, stratum radiatum of Ammon's horn, and subgranular zone of the dentate gyrus. Positive neurons were also conspicuous in the molecular layer of the dentate gyrus and in the pyramidal layer of CA3, sparse in the pyramidal layer of CA2 and CA1, and almost absent from presubiculum and parasubiculum. Numerous positive fibers were seen, especially in stratum radiatum and stratum lacunosum-moleculare of Ammon's horn. Double staining experiments demonstrated that nearly all NADPH diaphorase-positive neurons in the hippocampus also contained gamma-aminobutyric acid. On the basis of their morphology, distribution, and inhibitory neurotransmitter content, most NOS-positive cells in the hippocampus are probably local circuit neurons. These data suggest that nitric oxide in CA1 may function as a paracrine agent, rather than a spatially precise messenger, in long-term potentiation.

Amino Acid Oxidoreductases↗
PubMed1993

Cloned human brain nitric oxide synthase is highly expressed in skeletal muscle.

Complementary DNA clones corresponding to human brain nitric oxide (NO) synthase have been isolated. The deduced amino acid sequence revealed an overall identity with rat brain NO synthase of about 93% and contained all suggested consensus sites for binding of the co-factors. The cDNA transfected COS-1 cells showed significant NO synthase activity with the typical co-factor requirements. Unexpectedly, messenger RNA levels of this isoform of NO synthase was more abundant in human skeletal muscle than human brain. Moreover, we detected high NO synthase activity and the expressed protein in human skeletal muscle by Western blot analysis, indicating a possible novel function of NO in skeletal muscle.

Adolescent↗
PubMed1993

Nitric oxide synthase immunoreactivity in the rat, mouse, cat and squirrel monkey spinal cord.

The distribution of nitric oxide synthase-immunoreactive neurons was examined in the spinal cord of rats, mice, cats and squirrel monkeys at the light microscopic level. Some sections were processed for choline acetyltransferase immunoreactivity. Double-labeling techniques were used to assess possible co-localization of nitric oxide synthase and choline acetyltransferase immunoreactivity in the same spinal neurons. Nitric oxide synthase-immunoreactive neurons were concentrated in three fairly well-defined regions of the spinal cord of all species studied: (i) the intermediolateral cell column of the thoracic and sacral segments, (ii) lamina X of all segments, and (iii) the superficial layers of the dorsal horn of all segments. A few nitric oxide synthase-immunoreactive neurons were scattered in the deeper laminae and the ventral horn. There were fewer nitric oxide synthase-positive neurons in monkey spinal lamina X and dorsal horn than in similar locations of rodents and felines. Double-staining showed that not all choline acetyltransferase-positive neurons in the intermediate cell column and lamina X were nitric oxide synthase-immunoreactive. In the ventral horn, choline acetyltransferase-positive neurons (presumed motoneurons) were nitric oxide synthase-negative. In addition to cell bodies, nitric oxide synthase-positive fibers were scattered in the dorsal, lateral and ventral horns of all species. Finally, punctate nitric oxide synthase-immunoreactive fibers were seen traversing the dorsal, lateral and ventral white matter, and reaching the respective gray matter. The present study shows that, in spite of quantitative differences, the pattern of distribution of nitric oxide synthase-positive neurons in the spinal cord was similar across the four species. The concentration of nitric oxide synthase-positive neurons in the autonomic nuclei and laminae I, II and X of all four species underscores a prominent role of these neurons in visceral and sensory functions.

Amino Acid Oxidoreductases↗
PubMed1993

Nitroxergic autonomic neurones in rat spinal cord.

We have used a polyclonal monospecific antibody to rat cerebellum nitric oxide synthase type I (NOS-I, 160 kD) in combination with reduced NADPH-diaphorase histochemical reaction (NADPH-d) to verify colocalization of both NOS protein and NOS enzymatic activity in the rat spinal cord autonomic system. Strong immunoreactivity (IR) of NOS-I was clearly detected in the four main thoracolumbar autonomic nuclei in spinal cord layers of Rexed's laminae VI, VII and X. In all labelled neurones, NOS-I-IR colocalized with NADPH-d activity, suggesting coexistence of brain-specific NOS-I-like protein and its associated enzyme activity. For these neurones the new term 'nitroxergic' (i.e. NO-generating) neurones appears to be justified. Spinal cord nitroxergic neurones are part of a NO-mediated signal transduction pathway for control of the sympathetic 'outflow' to various peripheral target organs.

Amino Acid Oxidoreductases↗
PubMed1993

[Hemorheologic effects of hydroxyethyl starch 200/0.5, dextran 40, oxypolygelatine and full electrolyte solution over 48 hours].

Four patient groups (n = 28 patients) received in a randomised clinical trial a single intravenous infusion of 500 ml of 10% dextran 40, 3.5% oxypolygelatine, 6% hydroxyethyl starch 200/0.5 or saline solution, respectively. The haemorheological parameters haematocrit, plasma viscosity and erythrocyte aggregation were followed up during 48 hours. In our study oxypolygelatine showed better rheological results than HAES 200/0.5. Dextran 40 especially increased the plasma viscosity and erythrocyte aggregation, so that we cannot recommend this plasma substituent for hypervolemic haemodilution.

Adult↗
PubMed1993

[In vitro modification of plasma viscosity and erythrocyte aggregation by four plasma substitutes].

We tested the haemorheological effects of the addition of 3.5% oxypolygelatine, 10% dextran 40, 6% dextran 75 or 5% albumin, respectively, to fresh donor blood of 25 healthy young persons. We examined the aggregation and the viscosity of substituent plasma mixtures in such various, but constant volume relations as may be present during intravenous infusion. Albumin reduced viscosity and aggregation, but especially dextran 75 increased both parameters significantly.

Adult↗
PubMed1993

Elevated lipoprotein(a) is lowered by a cholesterol synthesis inhibitor in a normocholesterolaemic patient with premature myocardial infarction.

We have identified a 37-year-old patient suffering from two myocardial infarctions, with a markedly elevated lipoprotein(a) [Lp(a)] level and normal levels of cholesterol and triglycerides. Clinically this patient presented with xanthelasma and arcus lipoides corneae. After treatment with a cholesterol synthesis inhibitor (Pravastatin), the Lp(a) concentration in this patient was reduced significantly. This case report supports the hypothesis that elevated Lp(a) is an independent risk factor for coronary artery disease. The effect of the cholesterol synthesis inhibitor on Lp(a) may be due to the upregulation of the LDL-receptor, suggesting a role for LDL receptor in Lp(a) catabolism.

Adult↗
PubMed1992

Nitric oxide synthase in macula densa regulates glomerular capillary pressure.

Tubular-fluid reabsorption by specialized cells of the nephron at the junction of the ascending limb of the loop of Henle and the distal convoluted tubule, termed the macula densa, releases compounds causing vasoconstriction of the adjacent afferent arteriole. Activation of this tubuloglomerular feedback response reduces glomerular capillary pressure of the nephron and, hence, the glomerular filtration rate. The tubuloglomerular feedback response functions in a negative-feedback mode to relate glomerular capillary pressure to tubular-fluid delivery and reabsorption. This system has been implicated in renal autoregulation, renin release, and longterm body fluid and blood-pressure homeostasis. Here we report that arginine-derived nitric oxide, generated in the macula densa, is an additional intercellular signaling molecule that is released during tubular-fluid reabsorption and counters the vasoconstriction of the afferent arteriole. Antibody to rat cerebellar constitutive nitric oxide synthase stained rat macula densa cells specifically. Microperfusion of the macula densa segment of single nephrons with N omega-methyl-L-arginine (an inhibitor of nitric oxide synthase) or with pyocyanin (a lipid-soluble inhibitor of endothelium-derived relaxation factor) showed that generation of nitric oxide can vasodilate the afferent arteriole and increase glomerular capillary pressure; this effect was blocked by drugs that prevent tubular-fluid reabsorption. We conclude that nitric oxide synthase in macula densa cells is activated by tubular-fluid reabsorption and mediates a vasodilating component to the tubuloglomerular feedback response. These findings imply a role for arginine-derived nitric oxide in body fluid-volume and blood-pressure homeostasis, in addition to its established roles in modulation of vascular tone by the endothelium and in neurotransmission.

Amino Acid Oxidoreductases↗
PubMed1992

Nitric oxide synthase and GABA colocalize in lamina II of rat spinal cord.

A dense plexus of fibers in the substantia gelatinosa contains nitric oxide synthase (NOS). Using electron microscopic double-labeling immunocytochemistry for NOS combined with GABA or glutamate, we find that all NOS-positive terminals in this region also contain GABA but are not enriched in glutamate. In an attempt to verify that NOS-positive terminals do not originate from primary afferents, we combined NOS immunocytochemistry with anterograde tracing from the sciatic nerve. An intrinsic spinal origin for the NOS-positive plexus is suggested. The results are discussed in the light of the possible involvement of nitric oxide in hyperalgesia.

Afferent Pathways↗
PubMed1992

Colocalization of nitric oxide synthase and NADPH-diaphorase in the myenteric plexus of the rat gut.

The pattern of distribution and colocalization of nitric oxide-synthase (NOS) and NADPH-diaphorase in the myenteric plexus of whole-mount preparations of the antrum, duodenum, ileum, caecum, proximal colon and distal colon of the rat were investigated using immunohistochemical and histochemical staining techniques. Almost all the myenteric neurons that were NOS-positive in all regions of the gut examined were also stained for NADPH-diaphorase. However, in the stomach, duodenum and ileum, only a few of the NOS-positive nerve fibres in the tertiary and secondary plexuses and circular muscle layer were also stained for NADPH-diaphorase, whereas in the caecum and distal colon almost all the NOS-positive nerve fibres were also stained for NADPH-diaphorase. The results in the present study are consistent with the view that nitric oxide (NO) has a mediating role in gastrointestinal neurotransmission.

Amino Acid Oxidoreductases↗
PubMed1992

Nitric oxide synthase immunoreactivity and NADPH-diaphorase activity in a subpopulation of intrinsic neurones of the guinea-pig heart.

This is the first report of the presence of nitric oxide synthase (NOS) immunoreactivity and NADPH-diaphorase (NADPH-d) activity in a subpopulation of the intrinsic neurones that innervate the heart. A cytochemical technique to detect NADPH-d and antisera raised against purified rat cerebellar NOS were employed to examine the expression of these enzymes by cells in a dissociated cell culture preparation from newborn guinea-pig atria and interatrial septum. Comparison of the results obtained by these two techniques and double-labelling experiments indicate that a subpopulation of intracardiac neurones contain both NADPH-d and NOS. These results indicate that some intracardiac neurones are capable of synthesizing nitric oxide. This raises the possibility that nitric oxide plays a role in the neural control of the heart.

Amino Acid Oxidoreductases↗
PubMed1992

NO., CO and .OH. Endogenous soluble guanylyl cyclase-activating factors.

Several low molecular weight compounds are capable of activating soluble guanylyl cyclase. Recent evidence suggests that some of these are formed under physiological conditions: the nitric oxide radical, carbon monoxide and the hydroxyl radical. Thus, multiple signal transduction pathways appear to exist that form a family of guanylyl cyclase activating factors and thereby regulate the intracellular cyclic guanosine 3',5'-monophosphate level.

Animals↗
PubMed1992

Ca2+/calmodulin-dependent NO synthase type I: a biopteroflavoprotein with Ca2+/calmodulin-independent diaphorase and reductase activities.

NO synthase (NOS; EC 1.14.23) catalyzes the conversion of L-arginine into L-citrulline and a guanylyl cyclase-activating factor (GAF) that is chemically identical with nitric oxide or a nitric oxide-releasing compound (NO). Similar to the other isozymes of NOS that have been characterized to date, the soluble and Ca2+/calmodulin-regulated type I from rat cerebellum (homodimer of 160-kDa subunits) is dependent on NADPH for catalytic activity. The enzyme also possesses NADPH diaphorase activity in the presence of the electron acceptor nitroblue tetrazolium (NBT). We investigated the requirements of NOS and its content of the proposed additional cofactors tetrahydrobiopterin (H4biopterin) and flavins, further characterized the NADPH diaphorase activity, and quantified the NADPH binding site(s). Purified NOS type I Ca2+/calmodulin-independently bound the [32P]2',3'-dialdehyde analogue of NADPH (dNADPH), which, at near Km concentrations during 3-min incubations was utilized as a substrate and at higher concentrations or after prolonged incubations and cross-linking inhibited NOS activity. The NADPH diaphorase activity was Ca2+/calmodulin-independent, required higher NADPH concentrations than NOS activity, and was affected by dNADPH to a lesser degree. Divalent cations interfered with the diaphorase assay. Per dimer, native NOS contained about 1 mol each of H4biopterin, FAD, and FMN, classifying it as a biopteroflavoprotein, and incorporated 1 mol of dNADPH. No dihydrobiopterin (H2biopterin), biopterin, or riboflavin was detected. These findings suggest that NOS may share cofactors between two identical subunits via high-affinity binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗