0000000000636781
AUTHOR
Daniel Morales-cano
Antiproliferative effects of drugs affecting different signalling pathways on rat and human pulmonary artery smooth muscle cells
Current treatments for pulmonary arterial hypertension (PAH) include pulmonary vasodilators which may also inhibit PASMC proliferation. The aim of this study was to compare the antiproliferative effects of multiple drugs on rat and human PASMC (rPASMC and hPMASC, respectively) in vitro. rPASMCs and hPASMC were starved for 24 h, then treated with different inhibitors and incubated for 48 h in 1% foetal calf serum plus endothelin-1, 5-HT and U46619. Cell number was estimated by the MTT test. Viable cells increased by 160-180% in 48 h. Activation of the cGMP pathway with the soluble guanylyl cyclase activators riociguat and YC-1 (≤ 10 µM) or the cAMP pathway by the adenylyl cyclase activator f…
Activation of PPARβ/δ prevents hyperglycaemia-induced impairment of Kv7 channels and cAMP-mediated relaxation in rat coronary arteries.
PPARβ/δ activation protects against endothelial dysfunction in diabetic models. Elevated glucose is known to impair cAMP-induced relaxation and Kv channel function in coronary arteries (CA). Herein, we aimed to analyse the possible protective effects of the PPARβ/δ agonist GW0742 on the hyperglycaemic-induced impairment of cAMP-induced relaxation and Kv channel function in rat CA. As compared with low glucose (LG), incubation under high glucose (HG) conditions attenuated the relaxation induced by the adenylate cyclase activator forskolin in CA and this was prevented by GW0742. The protective effect of GW0742 was supressed by a PPARβ/δ antagonist. In myocytes isolated from CA under LG, forsk…
Riociguat versus sildenafil on hypoxic pulmonary vasoconstriction and ventilation/perfusion matching
Introduction Current treatment with vasodilators for pulmonary hypertension associated with respiratory diseases is limited by their inhibitory effect on hypoxic pulmonary vasoconstriction (HPV) and uncoupling effects on ventilation-perfusion (V'/Q'). Hypoxia is also a well-known modulator of the nitric oxide (NO) pathway, and may therefore differentially affect the responses to phosphodiesterase 5 (PDE5) inhibitors and soluble guanylyl cyclase (sGC) stimulators. So far, the effects of the sGC stimulator riociguat on HPV have been poorly characterized. Materials and methods Contraction was recorded in pulmonary arteries (PA) in a wire myograph. Anesthetized rats were catheterized to record …
Ceramide Mediates Acute Oxygen Sensing in Vascular Tissues
AbstractAims: A variety of vessels, such as resistance pulmonary arteries (PA) and fetoplacental arteries and the ductus arteriosus (DA) are specialized in sensing and responding to changes in oxygen tension. Despite opposite stimuli, normoxic DA contraction and hypoxic fetoplacental and PA vasoconstriction share some mechanistic features. Activation of neutral sphingomyelinase (nSMase) and subsequent ceramide production has been involved in hypoxic pulmonary vasoconstriction (HPV). Herein we aimed to study the possible role of nSMase-derived ceramide as a common factor in the acute oxygen-sensing function of specialized vascular tissues. Results: The nSMase inhibitor GW4869 and an anticera…