{'fraction_non_alphanumeric': 0.04383026242322725, 'fraction_numerical': 0.02512562814070352, 'mean_word_length': 4.951827242524917, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 1, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Prenatal Hypoxia Altered Angiotensin II-mediated Vasoconstrictions viaPKC/ERK/ROCK Pathways and Potassium Channels in Rat Offsrping Middle Cerebral Artery.

Adverse environmental factors or prenatal insults may cause developmental and pathological changes in the brain. Previous studies showed that a number of unfavorable prenatal factors might trigger the pathological changes of adult diseases such as hypertension and diabetes mellitus. It is rational that inner-utero hypoxia could be a common problem of prenatal insults-induced development. Hence, this study focused on prenatal hypoxia (PH) during pregnancy. Cerebral artery is sensitive to low oxygen and critical in the cerebral blood flow. As all known, potassium channels and protein kinase C (PKC)/extracellular signal-regulated kinase (ERK)/Rho kinase (ROCK) pathways play the vital role in the regulation of cerebral vasculature. However, there are very limited information about the regulations of potassium channels and PKC/ERK/ROCK signaling pathways on middle cerebral artery (MCA) form PH offspring. Therefore, the present study focused on the effect of PH on the MCA from the offspring, and its correlation with potassium channels and PKC/ERK/ROCK signaling pathways. Notably, vascular functions as well as several molecules in vessel tissue were affected by prenatal insults, which is related to RAS. Ang II can stimulate vasoconstrictions via three major pathways: 1) release of Ca from intracellular stores; 2) induce of trans-membrane influx of Ca predominantly through L-type Ca channels (Cav1.2); 3) activation of one or multiple subtypes of protein kinase C (PKC). The present study aimed to investigate the regulatory role of PKC/ERK/ROCK signaling pathway in Ang II--mediated vasoconstrictions in the MCA of the PH offspring. Rat offspring: Pregnant Sprague-Dawley rats from the Animal Center of Soochow University were housed at 22 °C with a 12-hour light/dark cycle. They were randomly divided into 2 groups: 1) Control group: treated as the same as the PH group except without hypoxia; 2) PH group: kept in chambers with 10.5% O2 from gestational day 5 to 21. All rats were given tap water and standard rat food during and after pregnancy. Five-month old male offspring were tested. All experimental procedures were approved by the Institutional Animal Care Committee and in accordance with the Guide for the Care and Use of Laboratory Animals (NIH Publication No. 85–23, 1996). Small segments of MCA (fourth-order branch) were isolated in Krebs-Henseleit solution, mounted in a multi-myograph system, and maintained in oxygenated KHS (95% O2–5% CO2) at 37 °C. Vessel tone was normalized by the maximum contraction elicited by 120.0 mmol/L KCl. After equilibration for 60 min, vessel rings were contracted with cumulative Ang II (10–10 mol/L). Losartan (AT1R antagonist, 10 μmol/L), PD123319 (AT2R antagonist, 10 μmol/L), or GF109203X (PKC antagonist, 1 μmol/L), was used for pre-treating segments for 30 min, respectively, before the adding of Ang II. Concentration-response curves to the PKC activator, phorbol 12, 13-dibutyrate (PDBu, 10–10 mol/L) were performed in the presence of the ERK antagonist U0126 (10 μmol/L) or the ROCK antagonist Y-27632 (1 μmol/L). Signals were recorded by Power-Lab system. RNA was isolated by Trizol. Reverse transcriptase was employed for oligo dT primed first-strand cDNA synthesis (Supplementary Table S1, available in www.besjournal.com). Real-time PCR was carried out on Mx3000P detection system (Stratagene) by EvaGreen dye (Biotium). ΔΔCt method was used to