PPAR-Independent Arterial Smooth Muscle Relaxant Effects of PPAR Agonists
Figure 4
Involvement of sGC in PPARα agonist mediated relaxations. Effect of sGC inhibitor 10−5 M ODQ pretreatment on GW7647 (a) and WY14643 (c) mediated relaxations (–5). Preincubation with ODQ resulted in a rightward shift in the GW7647 and WY14643 relaxation curves demonstrating the involvement of sGC. Using an EIA kit, cGMP levels were measured in aortic rings freshly isolated from WT mice under basal and stimulated conditions. (b) 10−5 M GW7647 (GW) elevated cGMP content in aortic homogenates 2.4-fold over basal levels, an effect that was inhibitable by pretreatment with the sGC inhibitor 10−5 M ODQ (). The NO• donor 10−6 M sodium nitroprusside (SNP) elevated cGMP by 5.5-fold in ODQ sensitive manner (). (d) Similar to GW, 10−4 M WY14643 (WY) also elevated cGMP by 2.4-fold and ODQ was able to attenuate this response to basal levels (). Compared to untreated control conditions, vehicle treatment (DMSO for GW and WY) did not alter basal cGMP levels. Data are means ± SEM. *Indicates P ≤ 0.05.
