Cyclooxygenases (COX) critically contribute to early placental programming in preeclampsia (PE) and sequent end-organ damage. Considering the frequent use of analgesics during pregnancy, we investigated whether gestational exposure to NSAIDs with different COX-1/COX-2 selectivity would variably modulate pre- and postnatal cardiovascular manifestations of PE. PE was induced by oral administration of L-NAME (50 mg/kg/day for 7 consecutive days) to pregnant rats starting from day 14 of gestation. Together with L-NAME, rats were treated simultaneously with celecoxib (10 mg/kg/day), diclofenac (0.5 mg/kg/day), or naproxen (1 mg/kg/day). Tail-cuff measurements at gestational day 20 revealed that PE rats exhibited significant increases and decreases in systolic blood pressure and heart rate, respectively, and these effects disappeared postnatally at weaning time. Such hemodynamic effects were not altered in rats treated concomitantly with individual analgesic drugs, except perhaps for an exaggerated increase in blood pressure observed in PE/celecoxib rats. Significantly higher levels of serum CK-MB, biomarker of cardiac damage, were demonstrated in weaning rats and this effect was suppressed by naproxen but not celecoxib or diclofenac. Additionally, naproxen was the most effective among all 3 NSAIDs in diminishing the elevated cardiac COX-1 and COX-2 activities and concomitant rises in PGE2, PGF2α, and thromboxane A2 levels. The upregulated gene expression of fms-like tyrosine kinase-1 and soluble endoglin, antiangiogenic factors, in hearts of PE rats were indiscriminately reduced by all 3 NSAIDs. In conclusion, compared with celecoxib and diclofenac, naproxen appears to be the most advantageous in reducing cardiac damage in weaning PE rats due to its synchronized downregulatory effects on COX and antiangiogenic pathways.
|Publication status||Published - May 2021|
|Event||Federation of American Societies of Experimental Biology - |
Duration: 18 May 2021 → …
|Conference||Federation of American Societies of Experimental Biology|
|Period||18/05/21 → …|