Aim: Progranulin (PGRN) is a novel adipocytokine with anti-inflammatory effects in vascular cells. The aim of this study was to clarify the effects of PGRN on reactivity of isolated blood vessel.
Methods: Isometric contraction of rat isolated superior mesenteric artery was measured.
Results: Pre-treatment with PGRN (10-100 ng mL-1 , 30 min) had no effect on noradrenaline- or 5-hydroxytriptamine-induced contraction. On the other hand, pre-treatment with PGRN (100 ng mL-1 ) augmented acetylcholine (ACh; 30 nm)-induced endothelium-dependent relaxation. Pre-treatment with PGRN (100 ng mL-1 ) augmented ACh (10 μm)-induced nitric oxide (NO)-mediated relaxation in the presence of indomethacin (10 μm), a cyclooxygenase inhibitor, and tetraethyl ammonium (10 mm), a non-selective potassium channel blocker. In contrast, pre-treatment with PGRN (100 ng mL-1 ) had no effect on ACh-induced endothelium-derived hyperpolarizing factor-mediated relaxation. Pre-treatment with PGRN (100 ng mL-1 ) had no effect on ACh (10 μm, 1 min)-induced endothelial NO synthase phosphorylation (at Ser1177) as determined by Western blotting. Pre-treatment with PGRN (100 ng mL-1 ) augmented an NO donor, sodium nitroprusside (SNP; 30 nm-1 μm)- but not a membrane-permeable cGMP analogue, 8-bromo-cGMP-induced relaxation. In the presence of 3-isobutyl-1-methylxanthine (100 μm), a phosphodiesterase inhibitor, pre-treatment with PGRN (100 ng mL-1 ) increased SNP (30 nm, 5 min)-induced cGMP production as determined by enzyme immunoassay.
Conclusion: We for the first time demonstrate that PGRN augments ACh-induced NO-mediated relaxation through the increases of cGMP production in smooth muscle. These results indicate PGRN as a possible pharmacotherapeutic target against cardiovascular diseases including obesity-related hypertension.
Keywords: NO/cGMP; adipocytokine; contractile reactivity; mesenteric artery.
© 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.