Figure 1.
Effect of sFlt-1 on blood pressure.
In vivo effect of sFlt-1 or vehicle (Cntrl) infusion during two weeks on mean arterial pressure (MAP). Data are presented as mean±SEM, N = 11–12, (ns) not significant, * p<0.05.
Figure 2.
Effect of COX inhibition on endothelin-1 concentration-response curves.
A) Concentration-response curve of endothelin-1 in isolated carotid arteries of vehicle-treated (Cntrl) and sFlt-1-treated mice. The inset depicts concentration-response curves of KCl (N = 15) and the α1-adrenergic receptor agonist phenylephrine (N = 8–9). B) Effect of pre-incubation with the non-selective cyclooxygenase-inhibitor indomethacin (indo; 10 μmol/L) on endothelin-1 concentration-response curves. Data are expressed as mean±SEM, *(maximal efficacy of sFlt-1 vs. Cntrl, N = 9–10, p<0.05), #(maximal efficacy of sFlt-1 vs. sFlt-1 + indo, N = 9–10, p<0.05), $(EC50 of sFlt-1 vs. sFlt-1 + indo and Cntrl vs. Cntrl + indo, p<0.05)
Figure 3.
Role of nitric oxide and the endothelium.
A) Effect of eNOS inhibition with L-NAME (N = 5) and endothelium (EC) denudation (N = 4) on ET-1 concentration-response curves in carotid segments of vehicle-treated mice (Cntrl). Data are expressed as mean±SEM, *(maximal efficacy of Cntrl vs. Cntrl + L-NAME and Cntrl vs. Cntrl + EC denuded, N = 9–5, p<0.05). B) Effect of L-NAME (N = 4) and EC denudation (N = 3) on ET-1 concentration-response curves in carotid segments of sFlt-1-treated mice. C) Metacholine concentration-response curve generated after pre-constriction with the α1-adrenergic receptor agonist phenylephrine. Data are expressed as mean±SEM,*(maximal relaxation sFlt-1 vs. Cntrl, N = 13–14, p<0.05).
Figure 4.
mRNA expression of ETA and ETB receptors and effect ETB receptor blockade.
A) Quantitative Real-Time PCR showing thoracic aorta mRNA expression profiles of Ednra and Ednrb in vehicle (Cntrl) and sFlt-1-treated mice normalized to Hprt mRNA levels. Data expressed as mean±SEM, *(Inset figure shows a two-fold increase in high-responders vs. Cntrl, N = 7–13, p<0.05), #(high-responders vs. low-responders, N = 7–5, p = 0.06). B) Effect of pre-incubation with the ETB receptor antagonist BQ788 on endothelin-1 concentration-response curves of carotid segments isolated from vehicle (Cntrl, N = 5) and sFlt-1-treated mice (N = 4). *(maximal efficacy of Cntrl vs. Cntrl + BQ788, N = 5–9, p<0.05), $(EC50 of sFlt-1 vs. sFlt-1 + BQ788 and Cntrl vs. Cntrl + BQ788, p<0.05)
Figure 5.
Effect of aspirin and picotamide on sFlt-1-induced BP elevation.
The in vivo effect of intervention with aspirin (30 mg/kg/day) or picotamide (5 mg/kg/day) during two weeks on mean arterial pressure (MAP). Data are expressed as mean±SEM, N = 7–12. *(sFlt-1 vs Cntrl, p<0.05 with one-way anova and Dunnets post-hoc test.