C: Constriction dose response to PE in aortic rings in the presence or absence of 10 mol/L indomethacin (= 8 to 9)
C: Constriction dose response to PE in aortic rings in the presence or absence of 10 mol/L indomethacin (= 8 to 9). or cardiac hypertrophy either or significance of this alternative mode of IL-6 activation is only fully appreciated when you consider the cellular distribution of both the cognate IL-6R and gp130. Although IL-6R displays a restricted expression profile, gp130 is ubiquitously expressed. IL-6 responses to low-dose Ang II, which causes hypertension and hypertrophy during a 7-day period and discloses that IL-6?/? mice are very well guarded against both responses 0.05 or less was considered statistically Tezosentan significant. Results Systolic BP Elevations to Ang II Are Attenuated in IL-6?/? Mice No significant difference was noted between basal BP of WT and IL-6?/? mice (101.7 1.4 mm Hg, = 14, versus 102.2 0.6 mm Hg, = 14, for WT and IL-6?/?, respectively, mean SEM; Physique 1A, days ?3 to ?1), and this remained unaltered after subcutaneous infusion of vehicle (saline) (Physique 1A). Infusion of Ang II (1.1 mg/kg?1/day?1) significantly increased systolic BP in WT mice from day +2 to +7 compared with WT controls (Physique 1A, mean maximal pressure 139.4 9.1 mm Hg days +2 to +6 versus 97 0.93 mm Hg days +2 to +6, 0.001, compare with day 0). In contrast, the BP increase observed in IL-6?/? mice was significantly reduced ( 0.01 compare days +5 to +6) when compared with WT mice. Further, in the IL-6?/? group there was no BP increase until Tezosentan Tezosentan day +4. These data demonstrate Ang II-dependent hypertension is usually reduced both in severity and onset in IL-6?/? mice. Open in a separate windows Physique 1 Ang II-dependent hypertension and hypertrophy is usually attenuated in IL-6?/? mice, and IL-6 = 6); , WT Ang II-infused group (= 8); ?, IL-6?/? sham group (= 6); , IL-6?/? Ang II-infused group (= 8). ? 0.001 compared with WT control group; 0.0001 compared with IL-6?/? group; 0.01 compared with NKSF2 WT Ang II-infused group; using two-way analysis of variance with Bonferronis posttest (mean SEM). B: Administration (intraperitoneally) of sgp130Fc inhibits Ang II-dependent hypertension in WT mice. Ang II (1.1 mg/kg per day) was infused into male, 10 to 12 weeks aged, WT mice by osmotic minipump with or without administration of sgp130Fc (intraperitoneal injection on days ?1 and +1 at 100 g/mouse and days +3 and +5 at 50 g/mouse), and BP was monitored as in A. ?, WT group (= 6); , WT Ang II-infused group (= 8); ?, WT sgp130-treated (= 5); and , WT Ang II-infused sgp130-treated (= 6). ? 0.0001 compared with WT Ang II-infused group; 0.05 compared with WT Ang II-infused group using two-way analysis of variance with Bonferronis posttest (mean SEM). C: Administration of sgp130Fc in IL-6?/? mice. Ang II (1.1 mg/kg per day) was infused into male, 10 to 12 weeks aged, IL-6?/? mice by osmotic minipump with or without administration of sgp130Fc (intraperitoneal injection on days ?1 and +1 at 100 g/mouse and days +3 and +5 at 50 g/mouse), and BP was monitored as in A. ?, IL-6?/? group (= 6); , IL-6?/? Ang II-infused group (= 8); ?, IL-6?/? sgp130-treated (= 5); and , IL-6?/? Ang II-infused sgp130-treated (= 6). D: Cardiac hypertrophy after Ang II infusion in WT and IL-6?/? mice. Heart and body weight was recorded and compared for each group at the end of the Tezosentan Ang II infusion period (= 12, mean SEM; ? 0.001, ?? 0.05, compared with WT group; Tezosentan unpaired Students = 6 individual animals, mean SEM; ? 0.001 compared with WT group. ?? 0.05, compared with WT group; unpaired Students 0.0001; 0.05 compare days +2 to +6), when compared with WT Ang II-treated mice (Determine 1B). There was no effect of sgp130Fc administered alone to WT mice (Physique 1B). These data demonstrate that IL-6 0.05; Physique 2H and data not shown). These data indicate that IL-6 deficiency results in significant.