0000000000953487
AUTHOR
Nicla Flacco
β-Adrenoceptors differentially regulate vascular tone and angiogenesis of rat aorta via ERK1/2 and p38
β-Adrenoceptors (β-ARs) modulate ERK1/2 and p38 in different cells, but little is known about the contribution of these signaling pathways to the function of β-ARs in vascular tissue. Immunoblotting analysis of rat aortic rings, primary endothelial (ECs) and smooth muscle cells (SMCs) isolated from aorta showed that β-AR stimulation with isoprenaline activated p38 in aortic rings and in both cultured cell types, whereas it had a dual effect on ERK1/2 phosphorylation, decreasing it in ECs while increasing it in SMCs. These effects were reversed by propranolol, which by itself increased p-ERK1/2 in ECs. Isoprenaline β-AR mediated vasodilation of aortic rings was potentiated by the ERK1/2 inhi…
The impact of alpha1-adrenoceptors up-regulation accompanied by the impairment of beta-adrenergic vasodilatation in hypertension
9 pages, 7 figures, 3 tables.-- PMID: 19060223 [PubMed]
Changes in Adrenoceptors and G-Protein-Coupled Receptor Kinase 2 in <smlcap>L</smlcap>-NAME-Induced Hypertension Compared to Spontaneous Hypertension in Rats
This work compares the expression of adrenoceptors (ARs) and G-protein-coupled receptor kinase (GRK) 2 (RT-PCR and immunoblotting) and functional responses in conductance (aorta) and resistance vessels (mesenteric resistance arteries; MRA) in two different models of rat hypertension: hypertension induced by chronic treatment with <smlcap>L</smlcap>-NAME (N<sup>G</sup>-nitro-<smlcap>L</smlcap>-arginine methyl-ester) (<smlcap>L</smlcap>-NAME-treated rats; LNHR), and genetically induced hypertension (spontaneously hypertensive rats; SHR). Changes found in the aorta, but not in the MRA, were: (1) a loss of contractile capacity, more evidently in α…
Distribución, función y vías de señalización de los adrenoceptores β a nivel vascular
Se ha analizado la contribución de los diferentes subtipos de adrenoceptores (AR) β (β1, β2 β3) en la vasodilatación, determinando su localización en las diferentes células vasculares y evaluando la implicación de las vías de señalización adenilato ciclasa (AC)/AMPc/PKA y/o NO/guanilato ciclasa soluble (GCs)/GMPc, en dos lechos vasculares representantes de: los vasos de resistencia, como la arteria mesentérica de resistencia (A.M.R.) de rata, y de conductancia, como la aorta de rata. Los resultados obtenidos muestran que, a pesar de que los tres subtipos de AR β se expresan en ambos vasos, su participación en la respuesta funcional, así como la vía de señalización utilizada, es diferente se…
α1-Adrenoceptors in the rat cerebral cortex: New insights into the characterization of α1L- and α1D-adrenoceptors
36 p., figuras y tablas, bibliografía
a1D-Adrenoceptors are responsible for the high sensitivity and the slow time-course of noradrenaline-mediated contraction in conductance arteries.
The objective of this study was to determine whether the different time-course characteristics of α1-adrenoceptor-mediated contraction in arteries can be related to the subtypes involved. Contractile responses to noradrenaline (NA) were compared with inositol phosphate accumulation and extracellular signal-regulated kinase (ERK)1/2 phosphorylation after α1-agonist stimuli in the same vessels in the presence or absence of α1-antagonists in rat or in α1-subtype knockout (KO) mice. Aorta, where α1D-AR is the main functional subtype, had higher sensitivity to NA (in respect of inositol phosphate [IP], pERK1/2, and contractile response) than tail artery, where the α1A-adrenoceptor subtype is pre…
Activation of α1A-adrenoceptors desensitizes the rat aorta response to phenylephrine through a neuronal NOS pathway, a mechanism lost with ageing
Background and purpose A NO-mediated desensitization of vasoconstrictor responses evoked by stimulation of α1 -adrenoceptors has been reported in different vessels. We investigated the involvement of each α1 -adrenoceptor subtype and constitutive NOS isoforms and the influence of ageing and hypertension on this process. Experimental approach Wistar and spontaneously hypertensive rats (SHR), 16, 32, 52 and 72 weeks-old, were used to evaluate the desensitization process. Expression of α1 -adrenoceptor subtypes, endothelial NOS (eNOS) and neuronal NOS (nNOS) were determined in rat aorta and left ventricle (LV). Expression levels were also evaluated in LV of a group of heart failure patients wi…
Different β-adrenoceptor subtypes coupling to cAMP or NO/cGMP pathways: implications in the relaxant response of rat conductance and resistance vessels
Background and Purpose To analyse the relative contribution of β1-, β2- and β3-adrenoceptors (Adrb) to vasodilatation in conductance and resistance vessels, assessing the role of cAMP and/or NO/cGMP signalling pathways. Experimental Approach Rat mesenteric resistance artery (MRA) and aorta were used to analyse the Adrb expression by real-time-PCR and immunohistochemistry, and for the pharmacological characterization of Adrb-mediated activity by wire myography and tissue nucleotide accumulation. Key Results The mRNAs and protein for all Adrb were identified in endothelium and/or smooth muscle cells (SMCs) in both vessels. In MRA, Adrb1 signalled through cAMP, Adrb3 through both cAMP and cGMP…