Fenofibrate increases neuronal vasoconstrictor response in mesenteric arteries from diabetic rats: Role of noradrenaline, neuronal nitric oxide and calcitonin gene-related peptide
Loading...
Full text at PDC
Publication date
2011
Advisors (or tutors)
Editors
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Citations
Exportar
Citation
del Campo L, Blanco-Rivero J, Balfagon G. Fenofibrate increases neuronal vasoconstrictor response in mesenteric arteries from diabetic rats: role of noradrenaline, neuronal nitric oxide and calcitonin gene-related peptide. Eur J Pharmacol. 2011 Sep;666(1-3):142-9. doi: 10.1016/j.ejphar.2011.03.056. Epub 2011 May 20.
Abstract
We evaluated the possible effects of long-term fenofibrate treatment on adrenergic, nitrergic and CGRP-ergic innervation function in mesenteric arteries from streptotozin-induced diabetic rats. We analysed the vasoconstrictor response to electrical field stimulation (EFS) and the effects of the α antagonist phentolamine, the calcitonin gene related peptide (CGRP) receptor antagonist CGRP (8-37) and the nitric oxide synthase (NOS) inhibitor L-NAME in segments from untreated and fenofibrate-treated (100 mg/kg/day) diabetic rats. The vasomotor responses to noradrenaline (NA), CGRP and the NO donor sodium nitroprusside (SNP) were analysed, and NA, CGRP, and NO releases were measured. Neuronal NOS (nNOS), phosphorylated nNOS (P-nNOS), and RAMP1 protein expression were also analysed. Fenofibrate enhanced EFS-induced contractions. Phentolamine reduced EFS-induced contractions more in segments from fenofibrate-treated than in untreated rats. Fenofibrate increased vasoconstrictor response to NA and did not modify NA release. L-NAME increased EFS-induced contractions to a higher extent in segments from fenofibrate-treated than untreated rats. Fenofibrate did not change the vasodilator response to SNP but increased EFS-induced nitric oxide release. CGRP (8-37) increased EFS-induced contractions less in segments from fenofibrate-treated rats. Fenofibrate increased the vasodilator response to CGRP and reduced CGRP release. P-nNOS and RAMP1 expression were increased in segments from fenofibrate-treated rats, while nNOS expression remained unmodified. Fenofibrate enhances the vasoconstrictor response to EFS in diabetic rats. This effect is the functional result of the modifications of at least: (i) adrenergic function, enhanced by increased sensitivity to noradrenaline; (ii) nitrergic function, enhanced by increased neuronal NO release; and (iii) CGRP function, decreased by a reduction in CGRP release.