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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, but Adrb2, did not activate nucleotide formation; isoprenaline relaxation was inhibited by propranolol (β1, β2), CGP20712A (β1), and SQ22536 (adenylyl cyclase inhibitor), but not by ICI118,551 (β2), SR59230A (β3), ODQ (soluble guanylyl cyclase inhibitor), L- NAME or endothelium removal. In aorta, Adrb1 signalled through cAMP, while β2- and β3-subtypes through cGMP; isoprenaline relaxation was inhibited by propranolol, ICI118,551, ODQ, L- NAME, and to a lesser extent, by endothelium removal. CL316243 (β3-agonist) relaxed aorta, but not MRA. Conclusion and Implication Despite all three Adrb subtypes being found in both vessels, Adrb1, located in SMCs and acting through the adenylyl cyclase/ cAMP pathway, are primarily responsible for vasodilatation in MRA. However, Adrb-mediated vasodilatation in aorta is driven by endothelial Adrb2 and Adrb3, but also by the Adrb2 present in SMCs, and is coupled to the NO/ cGMP pathway. These results could help to understand the different physiological roles played by Adrb signalling in regulating conductance and resistance vessels. [ABSTRACT FROM AUTHOR]

Background and Purpose: Mitochondrial dysfunction and inflammation contribute to a myriad of cardiovascular diseases. Deleterious crosstalk of mitochondria and persistent endoplasmic reticulum (ER) stress triggers oxidative stress, which is involved in the development of vascular diseases. This study determined if inhibition of mitochondrial stress reduces aneurysm development in angiotensin II (Ang II)-infused apolipoprotein-E-deficient (ApoE -/- ) mice and its effect on ER stress., Experimental Approach: The mitochondria-targeted tetrapeptide, Szeto-Schiller 31 (SS31), ameliorated mitochondrial dysfunction and the enhanced expression of ER stress markers triggered by Ang II in ApoE -/- mice, and limited plasmatic and vascular reactive oxygen species (ROS) levels. Interestingly, SS31 improved survival, reduced the incidence and severity of abdominal aortic aneurysm (AAA), and the Ang II-induced increase in aortic diameter as evaluated by ultrasonography, resembling the response triggered by the classic ER stress inhibitors tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyrate (PBA)., Key Results: Disorganization of the extracellular matrix, increased expression of metalloproteinases and pro-inflammatory markers and infiltration of immune cells induced by Ang II in the abdominal aorta were effectively reduced by SS31 and ER inhibitors. Further, C/EBP homologous protein (CHOP) deficiency in ApoE -/- mice attenuated Ang II-mediated increase in vascular diameter and incidence of AAA, suggesting its contribution to the favourable response induced by ER stress inhibition., Conclusions and Implications: Our data demonstrate that inhibition of mitochondrial stress by SS31 limits AAA formation and increases survival through a reduction of vascular remodelling, inflammation and ROS, and support that attenuation of ER stress contributes to the favourable response elicited by SS31., (© 2023 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background and Purpose: A NO-mediated desensitization of vasoconstrictor responses evoked by stimulation of α 1 -adrenoceptors has been reported in different vessels. We investigated the involvement of each α 1 -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 α 1 -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 with a wide age range., Key Results: Repeated application of phenylephrine decreased subsequent α 1 -adrenoceptor-mediated vasoconstriction by increasing nNOS protein expression in aorta, but not in tail or mesenteric resistance arteries, where mRNA levels of nNOS were undetectable. This desensitization process disappeared in the absence of endothelium or in the presence of L-NAME (100 μM), nNOS inhibitors, SMTC (1 μM) and TRIM (100 μM), and 5-methylurapidil (100 nM, α 1A -antagonist), but not BMY7378 (10 nM, α 1D -antagonist). The α 1A /nNOS-mediated desensitization was absent in aged SHR and Wistar animals, where the expression of α 1A -adrenoceptors was reduced in aorta and LV. In human LV, a negative correlation was found between age and α 1A -adrenoceptor expression., Conclusions and Implications: The α 1A -adrenoceptor subtype, through endothelial nNOS-derived NO, may act as a physiological 'brake' against the detrimental effects of excessive α 1 -adrenoceptor-mediated vasoconstriction. Reduced α 1A -adrenoceptor- and nNOS-mediated desensitization in aged patients could be involved in the age-dependent elevation of adrenergic activity., (© 2017 The British Pharmacological Society.)