Biomedical subjects

D Spina

Publications and source records attributed to D Spina.

At least 73 records · Page 4Linked to original sources

PubMed1996

Effects of neonatal immunization and repeated allergen exposure on airway responsiveness in the rabbit.

Neonatal immunization of rabbits has previously been shown to enhance airway responsiveness to inhaled histamine. We investigated the influence of this immunization protocol on pulmonary parameters after inhalation of histamine in littermate allergen-immunized, sham-immunized, and saline-injected rabbits. In spontaneously breathing rabbits, inhalation of histamine caused a concentration-dependent increase in total lung resistance (RL) and respiratory rate (RR) and a reduction in dynamic compliance (Cdyn). Allergen-immunized rabbits were significantly more responsive to histamine than their control littermates and saline-injected animals when the concentration-effect curves were analyzed in terms of changes in RL (P < 0.05), Cdyn (P < 0.05), and RR (P < 0.05) among these groups. The production of allergen-specific immunoglobulins in this model was not correlated to indexes of airway responsiveness (P > 0.05). The effect of inhaled AMP on pulmonary function in allergen-immunized and native animals was also examined. Inhalation of AMP failed to influence Cdyn but elicited significant non-concentration-dependent increases in total RL in allergen-immunized but not naive animals (P < 0.05). Inhalation of AMP also caused a concentration-dependent increase in RR in both allergen-immunized and naive rabbits that was not significantly different (P > 0.05). The influence of biweekly exposure to inhaled or systemic allergen in allergen-immunized rabbits was also examined. Neither repeated systemic nor aerosolized allergen exposure of neonatally immunized rabbits from 3 to 7 mo of age resulted in a further enhancement of airway responsiveness to inhaled histamine. These results suggest that neonatal immunization with Alternaria allergens enhances airway responsiveness to inhaled histamine and AMP. This airway hyperresponsiveness at 3 mo of age could not be enhanced further after chronic exposure to allergen.

Adenosine↗

PubMed1996

Abortive mitoses and nuclear DNA fragmentation in CD30+ large cells of Hodgkin's disease.

This study was undertaken to better comprehend the reasons for the scarcity of Hodgkin and Reed-Sternberg (H-RS) cells in Hodgkin's disease (HD) despite their expression of "proliferation-associated antigens". To this end, we assessed the relative frequency of mitotic phases and nuclear damage (detected by in situ end-labeling of DNA strand breaks) in CD30+ large cells of nodular sclerosis and mixed cellularity HD. Our results show that a) most CD30+ cells in HD exhibit abortive mitoses, with a highly significant arrest at the metaphase-ana/telophase transition, and b) many of these elements, i.e. mainly H-RS cells, show fragmentation of nuclear DNA, suggesting imminent or actual death. Percentages of CD30+ cells that entered mitosis and those with DNA strand breaks were of a similar order of magnitude and correlated significantly in a linear fashion. These findings are consistent with the concept that cell deletion is the major cause of the paucity of H-RS cells in HD.

Adolescent↗

PubMed1996

Proliferative activity, angiogenesis, and necrosis in peripheral nerve sheath tumors: a quantitative evaluation for prognosis.

Malignant peripheral nerve sheath tumors (MPNSTs) are distinguished from a control group of typical benign schwannomas and neurofibromas on the basis of a set of quantitatively evaluated parameters, i.e., the cell density; the number of mitoses and apoptotic bodies; the nuclear area and shape; the number and absolute and relative areas of silver-staining nucleolar organizer regions; necrosis; and angiogenesis. Only the extent of tumor necrosis, the mitotic rate, and the parameters related to silver-staining nucleolar organizer regions discriminate between less aggressive MPNSTs (disease-free patients after 4 years of follow-up) and more aggressive MPNSTs (with recurrences or metastases during the first 4 years of follow-up).

Adult↗

PubMed1995

Cell proliferation patterns and p53 expression in gastric dysplasia.

Gastric dysplasia (high-grade, HGD, and low-grade, LGD) and normal mucosa were tested for anti-p53, anti-Ki-67 and anti-PCNA monoclonal antibodies on paraffin sections, and for relative AgNOR area and number on semithin Epon-Araldite sections. The proliferative compartment in normal mucosa was restricted to the middle layer corresponding to the neck-isthmus region. In LGD and HGD there was an expansion of this compartment to the lower and upper layers of mucosa, and in HGD in particular to the upper layer. p53 was always negative in LGD as well as in normal mucosa, while it was positive in 34 out of 51 cases of HGD. The most discriminant variables between LGD and HGD were relative AgNOR area and the percentages of MIB-1, p53 and PCNA. In p53-positive HGD the highest percentages of PCNA and MIB-1 were in the middle and upper layers (PCNA) or the upper layer (MIB-1), while in p53-negative HGD cases cell proliferation was maximal in the middle layer, although also present in the upper layer. The majority of cases of LGD did not demonstrate cell proliferation in the upper layer, but 5 cases behaved similarly to the p53-negative HGD cases. No significant correlations were found among percentages of MIB-1 and of PCNA and relative AgNOR area and number.

Adenocarcinoma↗

PubMed1995

Presence of the bcl-2 protein and apoptosis in non-Hodgkin lymphomas with diffuse growth pattern.

In an attempt to further clarify the role of the apoptosis-counteracting protein bcl-2, non-Hodgkin lymphomas (NHL, n = 170) were examined immunohistochemically, across the boundaries of histologic classification, for the presence of this oncoprotein, in comparison with apoptotic indices (AI) and percentages of Ki-67+ cells (growth fraction). The results of this retrospective study revealed a highly significant inverse relationship ("mirror image") between the proportion of bcl-2+ cells and the AI per case. Both these parameters, although variable, clearly distinguished low- from high-grade-malignancy lymphomas according to the Kiel classification. Cluster analysis detected 2 separate groups of high-grade NHL, one with rather high AI and low percentages of bcl-2+ cells, comprising most anaplastic large-cell lymphomas, the other group with reverse characteristics. We found no correlation between the percentage of bcl-2+ cells per case and overall survival.

Apoptosis↗

PubMed1995

Low versus high cell turnover in diffusely growing non-Hodgkin's lymphomas.

Cell loss, perhaps as important as cell production in determining the size of an expanding cell population, has not usually been registered in quantitative cellular kinetic analyses of neoplastic disorders. The present retrospective study on various types and subtypes of non-Hodgkin's lymphomas (NHLs; n = 170) was designed to test the usefulness of a novel additional parameter, the 'turnover index' (TI), which is the sum per case of the mitotic index and the apoptotic index. Results document that TIs clearly distinguished between categories and subtypes of NHLs according to the Kiel classification. Cluster analysis of TIs plotted against the percentage of Ki-67-positive cells per case revealed that about one-third of the high-grade malignancy lymphomas actually belonged to the low-turnover lymphomas. Overall survival was longer in the low- than in the high-turnover group of lymphomas. Assessment of TIs can, for practical diagnostic purposes, be replaced by counting mitotic figures and apoptotic cells in several high-power fields. The TI concept may help to interpret the kinetics of NHLs in terms of accumulation vs. proliferation of cells.

Adolescent↗

PubMed1995

Regulation by phosphodiesterase isoenzymes of non-adrenergic non-cholinergic contraction in guinea-pig isolated main bronchus.

1. We have investigated the role of phosphodiesterase isoenzymes in modulating electric field stimulation (EFS), substance P and capsaicin-induced contraction of the guinea-pig isolated main bronchus. 2. Non-adrenergic non-cholinergic contractile responses were elicited by EFS (3 Hz, 20 s) in the guinea-pig isolated main bronchus in the presence of the non-selective muscarinic antagonist, atropine (0.1 microM), the non-selective beta-adrenoceptor antagonist, propranolol (1 microM), the neutral endopeptidase inhibitor, thiorphan (10 microM) and the cyclo-oxygenase inhibitor, indomethacin (5 microM). The type III, type III/IV, type IV and type V phosphodiesterase isoenzyme inhibitor, SKF 94836, benzafentrine, Ro-20-1724 and zaprinast respectively, significantly attenuated the contractile response to EFS. The IC50 (95% confidence limits) value for SKF 94836, benzafentrine, Ro-20-1724 and zaprinast was 8.3 microM (0.89-78); 0.7 microM (0.1-4.5); 0.5 microM (0.2-1.2) and 13 microM (2-87) respectively. 3. The phosphodiesterase isoenzyme inhibitors, SKF 94836, Ro-20-1724 and zaprinast, partially attenuated the contractile response to substance P (10 nM). Benzafentrine significantly inhibited the contractile response to substance P, yielding an IC50 value of 1.9 microM (0.9-3.8). 4. The phosphodiesterase isoenzyme inhibitor, Ro-20-1724 (0.1-100 microM) failed to reduce significantly the contractile potency of capsaicin (P > 0.05). In contrast, SKF 94836 (1 microM), benzafentrine (10 microM) and zaprinast (100 microM) significantly reduced the contractile potency of capsaicin (P < 0.05). 5 The selective phosphodiesterase isoenzyme inhibitors, SKF 94836, benzafentrine, Ro-20-1724 andzaprinast (0.01-100 microM) reversed in a concentration-dependent manner the contractile response toexogenously administered capsaicin (EC50) yielding ICm values of 3.91 microM (0.68-22); 3.37 microM (1.86-6.11); 0.366 microM (0.201-0.564) and 50.1 microM (18.6- 135) respectively.6 In conclusion, phosphodiesterase isoenzymes appear to regulate the contractile response to electricalfield stimulation and our results provide circumstantial evidence for a regulatory role ofphosphodiesterase type IV isoenzyme on sensory nerve function in vitro.

Animals↗

PubMed1995

Primary gastric lymphomas (MALTomas): a nuclear image analysis comparison with lymph node monocytoid B-cells and marginal zones of spleen and Peyer's patches.

Centrocyte-like cells of marginal zones of follicles of gastrointestinal lymphoid tissue, which have their analogous in marginal zone of splenic white pulp and in lymph node monocytoid B-lymphocytes, are thought to be the normal counterpart of lymphomas of MALT (MALTomas). However, the cell population of MALTomas is often polymorphic and also contains cells morphologically different from centrocytes. Since conventional morphologic analysis may not be accurate enough and the phenotype may change in different stages of B-cell lineage, the marginal zone of Peyer's patches (PMZ) and splenic white pulp (SMZ), the lymph node monocytoid B-lymphocytes (ML), 3 nodal monocytoid B-cell lymphomas (L) and 16 gastric MALTomas (M) were studied by means of automated nuclear image analysis for area, irregularity, and chromatin texture assessment. Immunophenotyping on paraffin sections and polymerase chain reaction (PCR) for detecting monoclonality and t(14-18) chromosome breakpoints at DNA levels, on paraffin section extractions, were also done. In 14 MALTomas, clonal Ig heavy chain rearrangement was detected and in none of these were found t(14-18) chromosome breakpoints. The nuclei of the control group (PMZ, SMZ and ML) showed the same morphologic characteristics, ie. size, irregularity, chromatin texture. MALTomas and nodal lymphomas were distributed into 3 clusters: (1) with larger nuclei, light chromatin (euchromatin-richer) (5 MALTomas, 2 nodal lymphomas together with the control group); (2) nuclei with the same area size, but darker (eterochromatin-richer) (6 MALTomas and 1 nodal lymphoma); (3) with smaller and darker nuclei (5 MALTomas). Chromatin textural differences were maintained in the same nuclear size class in the 3 clusters. Only a few MALTomas had nuclear features not significantly different from controls, inter-case and intra-case variability being evident.

B-Lymphocytes↗

PubMed1994

Spatial distribution of mitosis, apoptosis and small blood vessels in malignant diffuse follicular-center-cell lymphomas: a nearest-neighbor analysis.

To better comprehend the relationships between cell birth and cell death in neoplastic disorders, the topography of these events needs to be considered. We applied a computerized nearest-neighbor analysis to malignant, diffuse follicular-center-cell lymphomas in order to examine the spatial distribution of pyknotic (apoptotic) cells/bodies (A) and mitotic figures (M) in relation to capillaries (C) and venules (V). The results revealed a complex dispersion pattern, with significant aggregations of A and M, in addition to an even greater random distribution component. The greatest clustering displayed by A was around capillaries (A-C, 42% reduction of object frequency between the first and second distance class), followed by A-A (33%), A-V (24%) and A-M (12%). Additional values for mitotic figures were: M-M (45%), M-V (33%) and M-C (22%). These findings may reflect the relative importance of inherent properties of the neoplastic and host factors, respectively, in the regulation of cell birth and cell death rates.

Adult↗

PubMed1994

Poly-L-arginine-mediated release of acetylcholine from parasympathetic nerves in rat and guinea-pig airways.

1. The synthetic cationic polypeptide, poly-L-arginine (0.03-1 mg ml-1) induced concentration-dependent contraction of guinea-pig and rat isolated trachea. In guinea-pig isolated trachea, this response was attenuated in the presence of the muscarinic cholinoceptor antagonist, atropine (0.1 microM) and augmented by the acetylcholinesterase inhibitor, ecothiophate (0.1 microM). The neuronal sodium channel blocker, tetrodotoxin (3 microM) failed to alter the contractile response to poly-L-arginine and acetylcholine. 2. The contractile response to poly-L-arginine in rat isolated trachea was inhibited in the presence of atropine (0.1 microM) and the 5-hydroxytryptamine (5-HT) receptor antagonist, methysergide (1 microM). Treatment of rat tracheal preparations with capsaicin (100 microM) or tetrodotoxin (3 microM) failed to alter the contractile response to poly-L-arginine. In contrast, ecothiophate (0.1 microM) augmented the contractile response to poly-L-arginine in rat isolated trachea. 3. Electrical field stimulation (5 Hz, 2 min) of epithelium-denuded guinea-pig tracheal preparations preloaded with [3H]-choline resulted in a contractile response and the simultaneous efflux of radioactivity into the superfusate. Both these responses were abolished in the presence of tetrodotoxin (1.5 microM). Poly-L-arginine (1 mg ml-1) also increased the efflux of total radioactivity from epithelium-denuded guinea-pig isolated tracheal preparations preloaded with [3H]-choline, but this response was tetrodotoxin-insensitive. The negatively charged polyanion, heparin (1 mg ml-1) failed to increase significantly the efflux of radioactivity from epithelium-denuded preparations. 4.In conclusion, the synthetic cationic polypeptide, poly-L-arginine, caused contraction of guinea-pig isolated tracheal preparations via the release of acetylcholine from parasympathetic nerves. Similarly,poly-L-arginine-induced contraction of rat isolated trachea is secondary to the release of acetylcholine from parasympathetic nerves and/or the release of mast cell-derived 5-HT.

Acetylcholine↗

PubMed1994

The effect of allosteric antagonists in modulating muscarinic M2-receptor function in guinea-pig isolated trachea.

1. We have assessed the influence of a range of synthetic cationic polypeptides with putative inhibitory actions at prejunctional muscarinic M2-receptors on electrical field stimulation-induced contraction of guinea-pig isolated tracheal preparations. Electrical field stimulation of epithelium-denuded guinea-pig trachea resulted in frequency-dependent contractile responses. As expected, tracheal smooth muscle sensitivity to electrical field stimulation was increased in tissues pretreated with the muscarinic M2-receptor antagonist, gallamine. In contrast, gallamine did not significantly alter the contractile potency to acetylcholine. 2. Unlike gallamine, the synthetic cationic polypeptides, poly-L-arginine, poly-L-lysine, poly-D-lysine, the cationic dye ruthenium red and the anionic polysaccharide, heparin, failed to increase significantly tracheal smooth muscle sensitivity to electrical field stimulation. 3. Poly-L-arginine, ruthenium red and heparin had no effect on the contractile response to exogenously applied methacholine. 4. These data are consistent with the concept that in guinea-pig tracheal smooth muscle, gallamine is an allosteric antagonist of guinea-pig tracheal muscarinic M2-receptors, whereas the various cationic polypeptides and the polyanion, heparin, are not.

Allosteric Regulation↗

PubMed1994

Contractile properties of synthetic cationic polypeptides in guinea-pig isolated trachea.

1. The synthetic polypeptides, poly-L-arginine, poly-L-lysine and poly-D-lysine contract guinea-pig isolated trachea in a concentration-dependent, epithelium-independent manner. Indomethacin augmented the contractile response to poly-L-arginine. 2. The contractile response to poly-L-arginine was not significantly inhibited by nicardipine, a selective L-type calcium channel blocker or by the histamine H1-receptor antagonist, mepyramine nor significantly augmented by the neutral endopeptidase inhibitor, phosphoramidon. 3. The contractile response to poly-L-arginine was inhibited in a concentration-dependent manner by prior incubation of guinea-pig tracheal rings with a number of anionic polypeptides including, low molecular weight heparin, poly-L-aspartic acid and bovine serum albumin. 4. In vitro capsaicin-induced desensitization failed to attenuate the contractile response to poly-L-arginine, suggesting little, if any role for sensory neuropeptides in the functional response in the guinea-pig. 5. Synthetic polypeptides induce an epithelium-independent, charge-dependent contraction of guinea-pig isolated trachea.

Animals↗

PubMed1993

A novel animal model for investigating persistent airway hyperresponsiveness.

The present study investigates the development and maintenance of airway hyperresponsiveness in neonatally immunized rabbits. Rabbits were immunized within 24 hr of birth with the antigen Alternaria tenuis together with aluminum hydroxide as an adjuvant, followed by repeated antigen and adjuvant administration up to 3 months of age. Anesthetized, spontaneously breathing rabbits immunized according to this protocol exhibited a 3.7- (p < 0.01) and 1.8-fold (p < 0.05) increase in airway responsiveness to inhaled histamine when compared with groups of naive or sham-immunized rabbits, respectively. In the absence of further antigen challenge, these changes in airway responsiveness to histamine in a subpopulation of antigen-immunized rabbits persisted for up to 12 months of age. This hyperresponsiveness was not associated with an alteration in either total or differential inflammatory cell numbers as assessed by bronchoalveolar lavage (BAL), and no significant differences in isolated bronchial smooth muscle responsiveness to methacholine, histamine, theophylline, or electrical field stimulation were observed. These results demonstrate that neonatal immunization of rabbits with Alternaria tenuis can lead to the development of persistent airway hyperresponsiveness, and that the maintenance of this state is unrelated to either a detectable alteration in cellular infiltration within the airway lumen or changes in bronchial smooth muscle responsiveness. It is suggested that neonatal exposure to antigen and adjuvant may be important determinants for the development of persistent airway hyperresponsiveness. This animal model may provide a useful way to investigate the effects of drugs on airway hyperresponsiveness.

Alternaria↗

PubMed1993

Distinction between diffuse cutaneous malignant follicular center cell lymphoma and lymphoid hyperplasia by computerized nuclear image analysis.

The difficult differential diagnosis between the diffuse variants of cutaneous lymphoid hyperplasia (CLH; synonym; pseudolymphoma) and malignant follicular center cell lymphomas (FCCL) often requires a multidisciplinary approach. Eighteen CLH and 11 FCCL, diagnosed by conventional histology and immunophenotyping and subsequently examined with a polymerase chain reaction to show clonal immunoglobulin heavy-chain gene rearrangements, were subjected to a novel type of automated nuclear image analysis. Of all nuclear parameters tested in azure A-stained semithin sections, the mean nuclear profile area (TN) of lymphoid cells was the best criterion to distinguish between CLH and FCCL (p = 9 x 10(-6)). Additional distinctive features, in the order of decreasing significance, were the SD of TN; all chromatin textural parameters combined; and the light and the dark fractions of the central nuclear profile areas. Parameters related to the chromatin pattern were independent of nuclear profile size in FCCL, but not in CLH. Two lesions registered as CLH displayed the nuclear characteristics favoring this diagnosis, but showed B-cell monoclonality at the DNA level. In conclusion, computerized nuclear image analysis is a helpful additional diagnostic tool in the evaluation of diffuse CLH and cutaneous FCCL.

Adolescent↗

PubMed1993

Apoptotic index: discriminant feature for the differentiation of cutaneous diffuse malignant follicular center cell lymphomas from lymphoid hyperplasia.

Diffuse subtypes of cutaneous lymphoid hyperplasia (CLH; n = 18) and primary malignant follicular center cell lymphoma of the skin (FCCL, n = 11) were diagnosed by conventional histology, immunophenotyping on paraffin sections, and gene rearrangement analysis. We then counted on semithin, Azur A-stained sections of resin-re-embedded biopsy specimens the relative numbers of apoptotic bodies among all lymphoid cells (apoptotic index [AI]). The diagnostic value of AI was compared to that of mitotic indices (MI) and percentages of various cell types in the cutaneous infiltrate. Features of cellular infiltrates distinguishing to two groups of lesions, in the order of decreasing significance, were percent large lymphoid cells, percent medium-sized lymphoid cells (both higher in FCCL); percent small lymphoid cells, percent epithelioid/giant cells, and percent histiocytes/macrophages (all three higher in CLH). However, of all parameters tested, AI had the greatest discriminant value (median in FCCL 1.11%, in CLH 0.14%; p = 8 x 10(-6)). Two cases, diagnosed as CLH with all morphologic and immunologic methods used, showed B-cell monoclonality at the DNA level. Linear discriminant analysis determined the following order of distinctive power of variables: 1) AI; 2) MI; 3) percent small lymphoid cells; 4) percent medium-sized lymphoid cells; 5) percent large lymphoid cells; 6) percent epithelioid/giant cells; and 7) percent histiocytes/macrophages. The present study thus establishes AI as an important parameter in the differentiation of diffuse CLH from diffuse cutaneous FCCL.

Adult↗

PubMed1992

Phenotypic overlaps between pleomorphic malignant T-cell lymphomas and mixed-cellularity Hodgkin's disease.

Histologically diagnosed, or in part questionable, malignant pleomorphic peripheral T-cell lymphomas (pPTCLs, n = 16) and mixed-cellularity Hodgkin's disease (MCHD, n = 12) were objectively compared by the use of combined immunohistochemistry on paraffin sections, test-point analysis of tissue components, and semi-automated nuclear morphometry on semi-thin resin sections. Classical, qualitative histomorphological distinction of these sub-types of lymphomas proved to be valid and is probably still the best method. Quantitative discriminant features, in order of decreasing significance, were: (i) expression by large atypical cells (LACs) of CD45R0, CD43 and CD45 in pPTCLs, and of CD30 and CD15 in MCHD; (ii) means and standard deviations (SDs) of LAC nuclear-profile areas (greater in MCHD than in pPTCLs); (iii) expression of CD3 by LACs in pPTCLs; (iv) prominence of small lymphoid cells in MCHD; (v) higher percentage of medium-sized lymphoid cells in pPTCLs; and (vi) higher SDs of nuclear-profile circularity factor of small lymphoid cells in MCHD. The medians of the largest nucleolar profile areas in LACs per field did not differ in pPTCLs and MCHD, but dispersion of individual values towards higher levels was significantly greater in the latter. Stepwise discriminant analysis of test point and nucleometric variables that best distinguished pPTCLs from MCHD revealed considerable overlaps, and questionable cases tended to be intermediate between the two. In conclusion, our results confirm and expand the notion of intra-group heterogeneity, with indistinct borders and the existence of intermediate phenotypes between these two taxonomic categories of malignant lymphomas.

Adolescent↗

PubMed1992

Evidence that epithelium-dependent relaxation of vascular smooth muscle detected by co-axial bioassays is not attributable to hypoxia.

1. The present study was undertaken to examine further the contribution of hypoxia to airway epithelium-dependent relaxation of rat aorta in the co-axial bioassay. 2. Endothelium-denuded rat aorta contracted with phenylephrine (0.05 microM) relaxed in a time-dependent manner (t1/2 = 8.3 +/- 0.4 min, n = 38) when the bathing solution was bubbled with 95% N2 and 5% CO2. In co-axial bioassays, the t1/2 for histamine (100 microM; guinea-pig trachea)- and methacholine (100 microM; rabbit bronchus)- induced relaxation was 1.9 +/- 0.2 min (n = 14) and 1.2 +/- 0.1 min (n = 26), respectively. 3. Hypoxia-induced relaxation was not associated with a rise in intracellular guanosine 3':5'-cyclic monophosphate (cyclic GMP). This contrasts with previous findings of an elevation in cyclic GMP associated with epithelium-dependent relaxation of rat aorta in co-axial bioassays. 4. Hypoxia-induced vascular relaxation was antagonized by the ATP-sensitive K+ channel blocker, glibenclamide (100 microM). In contrast, glibenclamide (100 microM) failed to inhibit histamine (100 microM; guinea-pig trachea)- and methacholine (0.1-100 microM; rabbit bronchus)-induced release of epithelium-derived inhibitory factor (EpDIF), in co-axial bioassays. Glibenclamide (100 microM) antagonized BRL 38227 (lemakalin), but not isoprenaline-induced relaxation of phenylephrine-contracted rat aorta. 5. These data strongly suggest that the airway epithelium-dependent relaxant responses observed in co-axial bioassays cannot be attributed to hypoxia.

Animals↗

PubMed1992

Correlation between airway epithelium-induced relaxation of rat aorta in the co-axial bioassay and cyclic nucleotide levels.

1. In co-axial bioassays, in the presence of indomethacin, addition of histamine (100 microM) or methacholine (100 microM) to guinea-pig trachea produced an epithelium-dependent relaxation of precontracted rat aorta which was associated with an approximately 2 fold elevation in tissue levels of guanosine 3':5'-cyclic monophosphate (cyclic GMP). Removal of the airway epithelium abolished the histamine-induced relaxation of rat aorta and the associated increase in intracellular cyclic GMP. 2. Epithelium-dependent relaxation was not associated with altered adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels in rat aorta. Unstimulated intact or denuded guinea-pig trachea also did not affect the levels of cyclic AMP or cyclic GMP in rat aorta. 3. Methylene blue (10 microM) abolished the methacholine-induced, endothelium-derived relaxing factor (EDRF)-mediated rise in intracellular cyclic GMP in rat endothelium-intact aorta alone. In contrast, methylene blue (10 microM) did not affect the methacholine-induced epithelium-dependent rise in intracellular cyclic GMP in rat endothelium-denuded aorta in the co-axial bioassay. 4. Relaxation of the rat aorta without endothelium was associated with increased levels of cyclic GMP (but not cyclic AMP) in response to sodium nitroprusside (5 nM) and of cyclic AMP (but not cyclic GMP) in response to isoprenaline (1 microM). 5. These results provide evidence that the postulated epithelium-derived inhibitory factor (EpDIF) may produce relaxation of vascular tissue via elevation in cyclic GMP levels. Furthermore, some data suggest that EpDIF may act by stimulation of the particulate, rather than the soluble form of guanylate cyclase.

Animals↗