PMID- 37180728
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230920
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 14
DP  - 2023
TI  - Preeclamptic programming unevenly perturbs inflammatory and renal vasodilatory 
      outcomes of endotoxemia in rat offspring: modulation by losartan and 
      pioglitazone.
PG  - 1140020
LID - 10.3389/fphar.2023.1140020 [doi]
LID - 1140020
AB  - Introduction: Preeclampsia (PE) enhances the vulnerability of adult offspring to 
      serious illnesses. The current study investigated whether preeclamptic fetal 
      programming impacts hemodynamic and renal vasodilatory disturbances in endotoxic 
      adult offspring and whether these interactions are influenced by antenatal 
      therapy with pioglitazone and/or losartan. Methods: PE was induced by oral 
      administration of L-NAME (50 mg/kg/day) for the last 7 days of pregnancy. Adult 
      offspring was treated with lipopolysaccharides (LPS, 5 mg/kg) followed 4-h later 
      by hemodynamic and renovascular studies. Results: Tail-cuff measurements showed 
      that LPS decreased systolic blood pressure (SBP) in male, but not female, 
      offspring of PE dams. Moreover, PE or LPS reduced vasodilations elicited by 
      acetylcholine (ACh, 0.01-7.29 nmol) or N-ethylcarboxamidoadenosine (NECA, 
      1.6-100 nmol) in perfused kidneys of male rats only. The latter effects 
      disappeared in LPS/PE preparations, suggesting a postconditioning action for LPS 
      against renal manifestation of PE. Likewise, elevations caused by LPS in serum 
      creatinine and inflammatory cytokines (TNFalpha and IL-1beta) as well as in renal 
      protein expression of monocyte chemoattractant protein-1 (MCP-1) and AT1 
      receptors were attenuated by the dual PE/LPS challenge. Gestational pioglitazone 
      or losartan reversed the attenuated ACh/NECA vasodilations in male rats but 
      failed to modify LPS hypotension or inflammation. The combined gestational 
      pioglitazone/losartan therapy improved ACh/NECA vasodilations and eliminated the 
      rises in serum IL-1beta and renal MCP-1 and AT1 receptor expressions. Conclusion: 
      Preeclamptic fetal programming of endotoxic hemodynamic and renal manifestations 
      in adult offspring depends on animal sex and specific biological activity and are 
      reprogrammed by antenatal pioglitazone/losartan therapy.
CI  - Copyright (c) 2023 Morgaan, Sallam, El-Gowelli, El-Gowilly and El-Mas.
FAU - Morgaan, Hagar A
AU  - Morgaan HA
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria 
      University, Alexandria, Egypt.
FAU - Sallam, Marwa Y
AU  - Sallam MY
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria 
      University, Alexandria, Egypt.
FAU - El-Gowelli, Hanan M
AU  - El-Gowelli HM
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria 
      University, Alexandria, Egypt.
FAU - El-Gowilly, Sahar M
AU  - El-Gowilly SM
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria 
      University, Alexandria, Egypt.
FAU - El-Mas, Mahmoud M
AU  - El-Mas MM
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria 
      University, Alexandria, Egypt.
AD  - Department of Pharmacology and Toxicology, College of Medicine, Health Sciences 
      Center, Kuwait University, Kuwait City, Kuwait.
LA  - eng
PT  - Journal Article
DEP - 20230425
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC10166818
OTO - NOTNLM
OT  - adult offspring
OT  - blood pressure
OT  - endotoxemia
OT  - gestational therapy
OT  - preeclampsia
OT  - renal vasodilation
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/05/14 19:13
MHDA- 2023/05/14 19:14
PMCR- 2023/04/25
CRDT- 2023/05/14 12:09
PHST- 2023/01/08 00:00 [received]
PHST- 2023/04/17 00:00 [accepted]
PHST- 2023/05/14 19:13 [pubmed]
PHST- 2023/05/14 19:14 [medline]
PHST- 2023/05/14 12:09 [entrez]
PHST- 2023/04/25 00:00 [pmc-release]
AID - 1140020 [pii]
AID - 10.3389/fphar.2023.1140020 [doi]
PST - epublish
SO  - Front Pharmacol. 2023 Apr 25;14:1140020. doi: 10.3389/fphar.2023.1140020. 
      eCollection 2023.