| 1. |
- Zhang, Yaping, et al.
(författare)
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MAPK/NF-kappa B-dependent upregulation of kinin receptors mediates airway hyperreactivity: A new perspective for the treatment
- 2013
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Ingår i: Pharmacological Research. - : Elsevier BV. - 1096-1186 .- 1043-6618. ; 71, s. 9-18
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Forskningsöversikt (refereegranskat)abstract
- Airway hyperreactivity (AHR) is a major feature of asthmatic and inflammatory airways. Cigarette smoke exposure, and bacterial and viral infections are well-known environmental risk factors for AHR, but knowledge about the underlying molecular mechanisms on how these risk factors lead to the development of AHR is limited. Activation of intracellular mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-kappa B) and their related signal pathways including protein kinase C (PKC), phosphoinositide 3-kinase (PI3K) and protein kinase A (PKA) signaling pathways may result in airway kinin receptor upregulation, which is suggested to play an important role in the development of AHR. Environmental risk factors trigger the production of pro-inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha) and interleukins (ILs) that activate intracellular MAPK- and NF-kappa B-dependent inflammatory pathways, which subsequently lead to AHR via kinin receptor upregulation. Blockage of intracellular MAPK/NF-kappa B signaling prevents kinin B-1 and B-2 receptor expression in the airways, resulting in a decrease in the response to bradykinin (kinin B-2 receptor agonist) and des-Arg(9)-bradykinin (kinin B-1 receptor agonist). This suggests that MAPK- and NF-kappa B-dependent kinin receptor upregulation can provide a novel option for treatment of AHR in asthmatic as well as in other inflammatory airway diseases. (C) 2013 Elsevier Ltd. All rights reserved.
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| 2. |
- Cao, Lei, et al.
(författare)
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Secondhand cigarette smoke induces increased expression of contractile endothelin receptors in rat coronary arteries via a MEK1/2 sensitive mechanism
- 2021
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 55:1, s. 50-55
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Cigarette smoke, a strong risk factor for cardiovascular diseases, upregulates contractile endothelin (ET) receptors in coronary arteries. The present study examined the effects of second hand cigarette smoke exposure on the contractile endothelin receptors and the role of the MEK1/2 pathway in rat coronary arteries. Design: Rats were exposed to secondhand smoke (SHS) for 8 weeks followed by intraperitoneal injection of a MEK1/2 inhibitor, U0126 daily for another 4 weeks. Contractile responses of isolated coronary arteries were recorded by a sensitive wire myograph. The receptor protein expression levels were examined by Western blotting. Results: The results showed that SHS in vivo caused increased expression of ET receptors ETA and ETB, and that the MEK1/2 blocker U0126 significantly reversed SHS exposure-increased ETA-mediated contractile responses and protein levels. Similar alterations were observed in ETB receptors. U0126 showed dose-dependent effects on SHS-induced response on contractile property and protein levels of the ETB receptor. However, only the higher dose U0126 (15 mg/kg) had inhibitory effects on the ETA receptor. Conclusions: Taken together, our data show that SHS increases contractile ET receptors and MEK1/2 pathway inhibitor offsets SHS exposure-induced ETA and ETB receptor upregulation in rat coronary arteries.
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| 3. |
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| 4. |
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| 5. |
- Sohn, Iben, et al.
(författare)
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The effects of CGRP in vascular tissue - Classical vasodilation, shadowed effects and systemic dilemmas
- 2020
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999. ; 881
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Forskningsöversikt (refereegranskat)abstract
- Vascular tissue consists of endothelial cells, vasoactive smooth muscle cells and perivascular nerves. The perivascular sensory neuropeptide CGRP has demonstrated potent vasodilatory effects in any arterial vasculature examined so far, and a local protective CGRP-circuit of sensory nerve terminal CGRP release and smooth muscle cell CGRP action is evident. The significant vasodilatory effect has shadowed multiple other effects of CGRP in the vascular tissue and we therefore thoroughly review vascular actions of CGRP on endothelial cells, vascular smooth muscle cells and perivascular nerve terminals. The actions beyond vasodilation includes neuronal re-uptake and neuromodulation, angiogenic, proliferative and antiproliferative, pro- and anti-inflammatory actions which vary depending on the target cell and anatomical location. In addition to the classical perivascular nerve-smooth muscle CGRP circuit, we review existing evidence for a shadowed endothelial autocrine pathway for CGRP. Finally, we discuss the impact of local and systemic actions of CGRP in vascular regulation and protection from hypertensive and ischemic heart conditions with special focus on therapeutic CGRP agonists and antagonists.
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| 6. |
- Adner, Mikael, et al.
(författare)
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Human endothelin ETA receptor antisense oligodeoxynucleotides inhibit endothelin-1 evoked vasoconstriction
- 1994
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Ingår i: European Journal of Pharmacology. - 1879-0712. ; 261:3, s. 281-284
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Tidskriftsartikel (refereegranskat)abstract
- Antisense oligodeoxynucleotides to endothelin ETA receptor mRNA were used to characterize vascular smooth muscle receptors. The concentration-response curve showed a significant attenuation of endothelin-1-induced contraction in circular segments of the human superficial temporal artery. Endothelin ETB receptor antisense or mismatch oligodeoxynucleotides showed no alteration of the endothelin-1-induced contraction. Complementary experiments with the selective endothelin ETA receptor antagonist FR139317 demonstrated a shift of the concentration-response curve to the right in a competitive manner (pA2 = 6.93). The specific method of using the receptor antisense oligodeoxynucleotides approach revealed the presence of endothelin ETA receptors mediating contraction in the human superficial temporal artery.
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| 7. |
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| 8. |
- Andersson, Sven, et al.
(författare)
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Reduction of Homocysteine in Elderly with Heart Failure Improved Vascular Function and Blood Pressure Control but did Not Affect Inflammatory Activity.
- 2005
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7843. ; 97:5, s. 306-310
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that hyperhomocysteinaemia is common in elderly heart failure patients, and is associated with endothelial dysfunction, impaired vasodilatory capacity and a low-grade inflammation. In the present study we examined if supplementation with B6, B12 and folate could normalize the hyperhomocysteinaemia and if so, in turn, would improve the associated parameters. This was an open study without placebo control on heart failure patients with plasma homocysteine > 15 microM. Measurements of cutaneous vascular reactivity, blood pressure, inflammatory activity and endothelial function were performed before and after intervention with intra-individual comparisons. The treatment reduced homocysteine to near normal values and enhanced the hyperaemic response to acetylcholine related to the response to heat. The mean arterial blood pressure and pulse rate was reduced. There was no effect on inflammatory activity, plasma levels of von Willebrand factor, subjective health quality or the hyperaemic responses to sodium nitroprusside or local warming. Hyperhomocysteinaemia in heart failure patients is multifactorial in origin. Folate deficiency, inflammatory activity and reduced renal function could be contributing. It is suggested that supplementation with B-vitamins can improve the vasodilatory capacity and reduce the blood pressure but additional studies are required to confirm this.
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| 9. |
- Baun, Michael, et al.
(författare)
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Pharmacological characterization and expression of VIP and PACAP receptors in isolated cranial arteries of the rat
- 2011
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 670:1, s. 186-194
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Tidskriftsartikel (refereegranskat)abstract
- Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) are potent vasodilators in animals and humans. PACAP infusion but not VIP infusion precipitates migraine attacks in migraine patients. The vascular effects of VIP and the two varieties of PACAP (PACAP-27 and PACAP-38) were investigated versus selective antagonists in segments of rat middle cerebral arteries (MCA), basilar arteries (BA) and middle meningeal arteries (MMA) using myographs. The luminal and abluminal effects of VIP were studied using perfusion myograph. mRNA expression of the relevant receptors (VPAC(1), VPAC(2) and PAC(1)) was examined by in situ hybridization. There was no significant difference in relaxant potency of the peptides in the MCA. In BA the relaxant potency was VIP>PACAP-27 = PACAP-38. Relaxant responses were either absent or very weak in MMA. VIP was found to be somewhat more potent in BA than in the MCA. Maxadilan, a selective PAC(1)-receptor agonist, showed no relaxant effect in either vessel. The VPAC(2)-antagonist PG 99-465 alone proved ineffective in the MCA, while it had a weak effect on BA. The VPAC(1)-antagonist PG 97269 inhibited relaxation induced by both VIP and the PACAPs in cerebral vessels. In combination, the two antagonists demonstrated better effect than either alone. VIP applied luminally via perfusion myograph caused no dilatation, indicating lack of endothelial involvement. In situ hybridization demonstrated the presence of mRNA for all three receptors in the smooth muscle cells of the vessels. In conclusion, migraine-like headache induced by PACAP-38 infusion is unlikely to be caused by direct vasodilator action on intracranial vessels. (C) 2011 Elsevier B.V. All rights reserved.
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| 10. |
- Bengtsson, Christine, et al.
(författare)
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Effect of Medication on Microvascular Vasodilatation in Patients with Systemic Lupus Erythematosus
- 2010
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7843 .- 1742-7835. ; 107:6, s. 919-924
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the microvascular responses in the skin, to local heat, iontophoretically administered acetylcholine and to sodium nitroprusside in relation to cardiovascular damage in patients with systemic lupus erythematosus (SLE) and matched controls. We also wanted to examine if the ongoing medication in SLE patients influenced this vascular response. We investigated 30 women with SLE and compared them with 20 age and sex-matched controls. The cutaneous blood flow response to local heat (+44 degrees C), iontophoretically administered endothelium-dependent (acetylcholine), as well as independent (sodium nitroprusside) vasodilatation, was measured by laser Doppler flowmetry. Clinical data and medication were retrieved from the clinical database and patient records. The cutaneous microvascular reactivity did not differ between SLE patients and a group of matched controls nor did it correlate with cardiovascular damage [assessed by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI)]. However, patients on antimalarial drugs (hydroxychloroquine n = 8 and chloroquine diphosphate n = 3) responded more strongly to sodium nitroprusside (endothelium-independent vasodilatation) compared with those without antimalarial drugs (p < 0.01). The response to acetylcholine was higher among patients on warfarin compared with those without (p < 0.05), whereas glucocorticoid use (>= 5 mg daily) was associated with reduced response to acetylcholine (p < 0.05). Smokers in general tended to have a lower response to acetylcholine (p = 0.064). Smoking SLE patients versus non-smoking SLE patients had a significantly lower response to acetylcholine (p = 0.01). Medication with antimalarial drugs-enhanced endothelium-independent vasodilatation, while glucocorticoid use was associated with reduction and warfarin-treatment with enhancement of endothelium-dependent vasodilatation. Therefore, despite there is no difference in microvascular endothelium-dependent vasodilatation, other factors such as medication and smoking may affect vasodilatation in SLE patients.
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