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- Högestätt, Edward D., et al.
(författare)
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Involvement of sensory nerves in vasodilator responses to acetylcholine and potassium ions in rat hepatic artery
- 2000
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Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188. ; 130:1, s. 27-32
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Tidskriftsartikel (refereegranskat)abstract
- In the presence of ouabain (1 mM), acetylcholine and KCl (5 mM) evoked endothelium-independent relaxations in rat hepatic arteries. Treatment with capsaicin (10 μM), scopolamine (1 μM) or CGRP8-37 (3 μM) prevented these relaxations. Acetylcholine-induced relaxations in intact arterial segments in the presence of indomethacin (10 μM) and N(G)-nitro-L-arginine (0.3 mM) were only partially inhibited by ouabain plus BaCl2 (30 μM). However, ouabain plus BaCl2 almost abolished such relaxations in capsaicin-pre-treated preparations. In arteries without endothelium, the neurosecretagogue α-latrotoxin (1 nM) induced complete relaxations, which were abolished by CGRP8-37 or pre-treatment with capsaicin. α-Latrotoxin also induced a smooth muscle hyperpolarization (12 ± 2 mV), which was abolished by CGRP8-37. The ability of ouabain to disclose a CGRP-mediated neurogenic relaxation must be considered when this agent is used as a pharmacological tool. The results further suggest that CGRP is a nerve-derived hyperpolarizing factor in the rat hepatic artery.
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| 3. |
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| 4. |
- Johansson, Rebecka, et al.
(författare)
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Phenotypic modulation of cultured bladder smooth muscle cells and the expression of inducible nitric oxide synthase.
- 2004
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Ingår i: American Journal of Physiology: Regulatory, Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 286:4, s. 642-648
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Tidskriftsartikel (refereegranskat)abstract
- Phenotypic modulation of smooth muscle is associated with various pathological conditions, including bladder dysfunction. Cytoskeletal dynamics modulate the cell phenotype and were recently shown to be involved in regulation of inducible nitric oxide synthase ( iNOS). We tested the hypothesis that the cell differentiation status affects iNOS expression, and that iNOS is preferentially expressed in immature dedifferentiated bladder smooth muscle cells (BSMC). Isolated rat BSMC were put into different stages of differentiation by serum deprivation on laminin-coated plates in the presence of IGF-I and by interaction with Rho signaling and actin polymerization. iNOS and smooth muscle-myosin heavy chain (SM-MHC) protein expression were investigated with Western blot analysis. Our results showed iNOS protein in BSMC exposed to interleukin-1beta ( 2 ng/ml) + TNF-alpha ( 50 ng/ml). Growth of BSMC in serum-free medium on laminin in the presence of IGF-I increased SM-MHC expression, whereas cytokine-induced iNOS was inhibited. Disruption of F-actin with latrunculin B ( 0.5 muM) potentiated iNOS expression and decreased SM-MHC expression. Rho inhibition with C3 (2.5 mug/ml) increased iNOS expression, whereas SM-MHC expression was slightly decreased. Rho-kinase inhibition with Y-27632 ( 10 muM) mediated a decrease in iNOS and a slight increase in SM-MHC expression. In conclusion, the capacity of BSMC to express iNOS was negatively correlated to differentiation status measured as SM-MHC expression. Actin cytoskeletal dynamics and Rho signaling are involved in regulation of cytokine-induced iNOS expression in BSMC. Phenotypic changes and impairment in actin cytoskeleton formation may potentiate cytokine activation and in turn increase nitric oxide production in the bladder during disease.
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| 5. |
- Johansson, Rebecka
(författare)
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Regulation of inducible nitric oxide synthase - Consequences in experimental models of bladder disease
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Inducible nitric oxide synthase (iNOS) expression is associated with various pathophysiological conditions in the lower urinary tract. The aims of this thesis have been to investigate the regulation of iNOS in bladder smooth muscle cells and the consequences on neuromuscular regulation, cell growth and differentiation. Primary cultures of rat bladder smooth muscle cells (BSMC) expressed iNOS mRNA and protein upon stimulation with the cytokines IL-1β and TNF-alpha in combination. No constitutive isoforms of NOS were detected at the mRNA level. BSMC were put into different stages of differentiation. The capacity of BSMC to express iNOS was negatively correlated to differentiation status measured as smooth muscle myosin-heavy chain expression. iNOS was shown to be preferentially expressed in immature dedifferentiated BSMC. Actin cytoskeletal dynamics and Rho signalling were involved in regulation of cytokine-induced iNOS expression in BSMC. Phenotypic changes and impairment in actin cytoskeletal formation may potentiate cytokine activation and in turn increase NO production during bladder disease. The consequences of iNOS induction on bladder neuromuscular function were investigated by incubating isolated rat bladder strips with cytokines and recording the mechanical activity in organ baths. iNOS protein was observed in the smooth muscle layer in cytokine stimulated bladder strips. Nerve-mediated, but not acetylcholine-mediated, contraction of the bladder was impaired in bladder strips exposed to cytokines. This impairment was restored by the iNOS inhibitor aminoguanidine and partially by the neurotrophic factor BDNF. iNOS induction affected bladder function and bladder nerves were more sensitive to NO exposure than smooth muscle. The activity and expression of different NOS isoforms were investigated in an in vivo model of bladder hypertrophy induced by urethral obstruction in rats. During obstruction the nNOS activity decreased whereas iNOS activity increased initially. The total NOS activity was decreased. iNOS was expressed in smooth muscle, urothelium and inflammatory cells. Exogenous NO exposure decreased DNA- and protein-synthesis and stimulated differentiation in cultured BSMC. The results indicate that the decreased NO production during obstruction may stimulate a growth response and phenotypic changes in the bladders smooth muscle. The results in this thesis show that the smooth muscle in the bladder should be considered as a source of iNOS expression and NO production during inflammation. Neuronally derived NO is suggested to be involved in bladder smooth muscle physiology by maintaining and stabilizing the smooth muscle phenotype.
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