TY - JOUR
T1 - Vasorelaxant and antiaggregatory actions of the nitroxyl donor isopropylamine NONOate are maintained in hypercholesterolemia
AU - Bullen, Michelle
AU - Miller, Alyson
AU - Dharmarajah, Janahan
AU - Drummond, Grant
AU - Sobey, Christopher
AU - Kemp, Barbara Kathryn
PY - 2011
Y1 - 2011
N2 - Nitroxyl (HNO) displays pharmacological and therapeutic actions distinct from those of its redox sibling nitric oxide (NO(.)). It remains unclear, however, whether the vasoprotective actions of HNO are preserved in disease. The ability of the HNO donor isopropylamine NONOate (IPA/NO) to induce vasorelaxation, its susceptibility to tolerance development and anti-aggregatory actions were compared to those of the clinically-used NO(.) donor, glyceryl trinitrate (GTN), in hypercholesterolemic mice. The vasorelaxant and anti-aggregatory properties of IPA/NO and GTN were examined in isolated carotid arteries and washed platelets, respectively, from male C57BL/6J mice maintained on either a normal (WT-ND) or high fat diet (WT-HFD, 7 weeks) and apolipoprotein E-deficient mice (ApoE(-/-)-HFD, 7 weeks). In WT-ND mice, IPA/NO (0.1-30 mumol/L) induced concentration-dependent vasorelaxation and inhibition of collagen (30 mug/ml)-stimulated platelet aggregation, which was predominantly soluble guanylyl cyclase/cGMP-dependent. Compared to WT-HFD, ApoE(-/-)-HFD mice displayed an increase in total plasma cholesterol levels (P
AB - Nitroxyl (HNO) displays pharmacological and therapeutic actions distinct from those of its redox sibling nitric oxide (NO(.)). It remains unclear, however, whether the vasoprotective actions of HNO are preserved in disease. The ability of the HNO donor isopropylamine NONOate (IPA/NO) to induce vasorelaxation, its susceptibility to tolerance development and anti-aggregatory actions were compared to those of the clinically-used NO(.) donor, glyceryl trinitrate (GTN), in hypercholesterolemic mice. The vasorelaxant and anti-aggregatory properties of IPA/NO and GTN were examined in isolated carotid arteries and washed platelets, respectively, from male C57BL/6J mice maintained on either a normal (WT-ND) or high fat diet (WT-HFD, 7 weeks) and apolipoprotein E-deficient mice (ApoE(-/-)-HFD, 7 weeks). In WT-ND mice, IPA/NO (0.1-30 mumol/L) induced concentration-dependent vasorelaxation and inhibition of collagen (30 mug/ml)-stimulated platelet aggregation, which was predominantly soluble guanylyl cyclase/cGMP-dependent. Compared to WT-HFD, ApoE(-/-)-HFD mice displayed an increase in total plasma cholesterol levels (P
UR - http://ajpheart.physiology.org/content/301/4/H1405.full.pdf+html
U2 - 10.1152/ajpheart.00489.2011
DO - 10.1152/ajpheart.00489.2011
M3 - Article
VL - 301
SP - H1405 - H1414
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
SN - 0363-6135
IS - 4
ER -