CoChat
Sign Up
Cited by 34Birth, Development, and HealthAir Quality and Health ImpactsBlood Pressure and Hypertension Studies

In Utero Exposure to Fine Particulate Matter Causes Hypertension Due to Impaired Renal Dopamine D1 Receptor in Offspring

Open access
Ye, Zhengmeng, Lu, Xi, Deng, Yi, Wang, Xinquan, Zheng, Shuo, Ren, Hongmei, Zhang, Miao, Chen, Tingting +3 more·2018·Cellular Physiology and Biochemistry
DOI 10.1159/000488418PMC PMC6437669
Open this paper in CoChat — free account

Abstract

Background/Aims: Adverse environment in utero can modulate adult phenotypes including blood pressure. Fine particulate matter (PM2.5) exposure in utero causes hypertension in the offspring, but the exact mechanisms are not clear. Renal dopamine D1 receptor (D1R), regulated by G protein-coupled receptor kinase type 4 (GRK4), plays an important role in the regulation of renal sodium transport and blood pressure. In this present study, we determined if renal D1R dysfunction is involved in PM2.5–induced hypertension in the offspring. Methods: Pregnant Sprague–Dawley rats were given an oropharyngeal drip of PM2.5 (1.0 mg/kg) at gestation day 8, 10, and 12. The blood pressure, 24-hour sodium excretion, and urine volume were measured in the offspring. The expression levels of GRK4 and D1R were determined by immunoblotting. The phosphorylation of D1R was investigated using immunoprecipitation. Plasma malondialdehyde and superoxide dismutase levels were also measured in the offspring. Results: As compared with saline-treated dams, offspring of PM2.5-treated dams had increased blood pressure, impaired sodium excretion, and reduced D1R-mediated natriuresis and diuresis, accompanied by decreased renal D1R expression and GRK4 expression. The impaired renal D1R function and increased GRK4 expression could be caused by increased reactive oxidative stress (ROS) induced by PM2.5 exposure. Administration of tempol, a redox-cycling nitroxide, for 4 weeks in the offspring of PM2.5-treated dam normalized the decreased renal D1R expression and increased renal D1R phosphorylation and GRK4 expression. Furthermore, tempol normalized the increased renal expression of c-Myc, a transcription factor that regulates GRK4 expression. Conclusions: In utero exposure to PM2.5 increases ROS and GRK4 expression, impairs D1R-mediated sodium excretion, and increases blood pressure in the offspring. These studies suggest that normalization of D1R function may be a target for the prevention and treatment of the hypertension in offspring of mothers exposed to PM2.5 during pregnancy.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1159/000488418

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 51

  1. [1]Poulter NR, Prabhakaran D, Caulfield M: Hypertension. Lancet 2015; 386: 801– 812. 25832858
  2. [2]Arima H, Murakami Y, Lam TH, Kim HC, Ueshima H, Woo J, Suh I, Fang X, Woodward M; Asia Pacific Cohort Studies Collaboration: Effects of prehypertension and hypertension subtype on cardiovascular disease in the Asia-Pacific Region. Hypertension 2012; 59: 1118– 1123. 22547441
  3. [3]Ritz E, Amann K, Koleganova N, Benz K: Prenatal programming-effects on blood pressure and renal function. Nat Rev Nephrol 2011; 7: 137– 144. 21283139
  4. [4]Zandi-Nejad K, Luyckx VA, Brenner BM: Adult hypertension and kidney disease: the role of fetal programming. Hypertension 2006; 47: 502– 508. 16415374
  5. [5]Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME: Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ 1989; 298: 564– 567. 2495113 PMC1835925
  6. [6]Eriksson J, Forsén T, Tuomilehto J, Osmond C, Barker D: Fetal and childhood growth and hypertension in adult life. Hypertension 2000; 36: 790– 794. 11082144
  7. [7]Law CM, de Swiet M, Osmond C, Fayers PM, Barker DJ, Cruddas AM, Fall CH: Initiation of hypertension in utero and its amplification throughout life. BMJ 1993; 306: 24– 27. 8435572 PMC1676382
  8. [8]van Rossem L, Rifas-Shiman SL, Melly SJ, Kloog I, Luttmann-Gibson H, Zanobetti A, Coull BA, Schwartz JD, Mittleman MA, Oken E, Gillman MW, Koutrakis P, Gold DR: Prenatal air pollution exposure and newborn blood pressure. Environ Health Perspect 2015; 123: 353– 359. 25625652 PMC4384198
  9. [9]Tanwar V, Gorr MW, Velten M, Eichenseer CM, Long VP 3rd, Bonilla IM, Shettigar V, Ziolo MT, Davis JP, Baine SH, Carnes CA, Wold LE: In utero particulate matter exposure produces heart failure, electrical remodeling, and epigenetic changes at adulthood. J Am Heart Assoc 2017; 6 pii:e005796. PMC5533043 28400369
  10. [11]Harris RC, Zhang MZ: Dopamine, the kidney, and hypertension. Curr Hypertens Rep 2012; 14: 138– 143. 22407378 PMC3742329
  11. [12]Pinto V, Pinho MJ, Soares-da-Silva P: Renal amino acid transport systems and essential hypertension. FASEB J 2013; 27: 2927– 2938. 23616567
  12. [13]Carey RM: Theodore Cooper Lecture: Renal dopamine system: paracrine regulator of sodium homeostasis and blood pressure. Hypertension 2001; 38: 297– 302. 11566894
  13. [14]Zeng C, Jose PA: Dopamine receptor: important antihypertensive counterbalance against hypertensive factors. Hypertension 2011; 57: 11– 17. 21098313 PMC3021462
  14. [15]Watanabe H, Xu J, Bengra C, Jose PA, Felder RA: Desensitization of human renal D1 dopamine receptors by G protein-coupled receptor kinase 4. Kidney Int 2002; 62: 790– 798. 12164861
  15. [16]Harris RC: Abnormalities in renal dopamine signaling and hypertension: the role of GRK4. Curr Opin Nephrol Hypertens 2012; 21: 61– 65. 22123211 PMC3286360
  16. [17]Yang J, Villar VA, Jones JE, Jose PA, Zeng C: G protein-coupled receptor kinase 4: role in hypertension. Hypertension 2015; 65: 1148– 1155. 25870190 PMC6350509
  17. [18]Chugh G, Lokhandwala MF, Asghar M: Altered functioning of both renal dopamine D1 and angiotensin II type 1 receptors causes hypertension in old rats. Hypertension 2012; 59: 1029– 1036. 22411927 PMC3331925
  18. [19]Mirowsky JE, Jin L, Thurston G, Lighthall D, Tyner T, Horton L, Galdanes K, Chillrud S, Ross J, Pinkerton KE, Chen LC, Lippmann M, Gordon T: In vitro and in vivo toxicity of urban and rural particulate matter from California. Atmos Environ (1994) 2015: 103: 256– 262. PMC4606878 26478712
  19. [20]Cuevas AK, Niu J, Zhong M, Liberda EN, Ghio A, Qu Q, Chen LC: Metal rich particulate matter impairs acetylcholine-mediated vasorelaxation of microvessels in mice. Part Fibre Toxicol 2015; 12: 14. 26041432 PMC4456050
  20. [21]Cao XN, Yan C, Liu DY, Peng JP, Chen JJ, Zhou Y, Long CL, He DW, Lin T, Shen LJ, Wei GH: Fine particulate matter leads to reproductive impairment in male rats by overexpressing phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Toxicol Lett 2015; 237: 181– 190. 26115885
  21. [22]Rao GV, Tinkle S, Weissman DN, Antonini JM, Kashon ML, Salmen R, Battelli LA, Willard PA, Hoover MD, Hubbs AF: Efficacy of a technique for exposing the mouse lung to particles aspirated from the pharynx. J Toxicol Environ Health A 2003; 66: 1441– 1452. 12857634
  22. [23]Miller MR, McLean SG, Duffin R, Lawal AO, Araujo JA, Shaw CA, Mills NL, Donaldson K, Newby DE, Hadoke PW: Diesel exhaust particulate increases the size and complexity of lesions in atherosclerotic mice. Part Fibre Toxicol 2013; 10: 61. 24330719 PMC3907045
  23. [24]Wang X, Luo H, Chen C, Chen K, Wang J, Cai Y, Zheng S, Yang X, Zhou L, Jose PA, Zeng C: Prenatal lipopolysaccharide exposure results in dysfunction of the renal dopamine D1 receptor in offspring. Free Radic Biol Med 2014; 76: 242– 250. 25236748 PMC6873924
  24. [25]Felder RA, Sanada H, Xu J, Yu PY, Wang Z, Watanabe H, Asico LD, Wang W, Zheng S, Yamaguchi I, Williams SM, Gainer J, Brown NJ, Hazen-Martin D, Wong LJ, Robillard JE, Carey RM, Eisner GM, Jose PA: G protein-coupled receptor kinase 4 gene variants in human essential hypertension. Proc Natl AcadSci U S A 2002; 99: 3872– 3877. PMC122616 11904438
  25. [26]Padia SH, Kemp BA, Howell NL, Keller SR, Gildea JJ, Carey RM: Mechanisms of dopamine D(1) and angiotensin type 2 receptor interaction in natriuresis. Hypertension 2012; 59: 437– 445. 22203736 PMC3279722
  26. [27]Salomone LJ, Howell NL, McGrath HE, Kemp BA, Keller SR, Gildea JJ, Felder RA, Carey RM: Intrarenal dopamine D1-like receptor stimulation induces natriuresis via an angiotensin type-2 receptor mechanism. Hypertension 2007; 49: 155– 161. 17116755
  27. [28]Zeng C, Luo Y, Asico LD, Hopfer U, Eisner GM, Felder RA, Jose PA: Perturbation of D1 dopamine and AT1 receptor interaction in spontaneously hypertensive rats. Hypertension 2003; 42: 787– 792. 12900438
  28. [29]Ecelbarger CA, Kim GH, Terris J, Masilamani S, Mitchell C, Reyes I, Verbalis JG, Knepper MA: Vasopressin-mediated regulation of epithelial sodium channel abundance in rat kidney. Am J Physiol Renal Physiol 2000; 279: F46– F53. 10894786
  29. [30]Zeng C, Yang Z, Wang Z, Jones J, Wang X, Altea J, Mangrum AJ, Hopfer U, Sibley DR, Eisner GM, Felder RA, Jose PA: Interaction of angiotensin II type 1 and D5 dopamine receptors in renal proximal tubule cells. Hypertension 2005; 45: 804– 810. 15699451
  30. [31]Soto SF, Melo JO, Marchesi GD, Lopes KL, Veras MM, Oliveira IB, Souza RM, de Castro I, Furukawa LNS, Saldiva PHN, Heimann JC: Exposure to fine particulate matter in the air alters placental structure and the renin-angiotensin system. PLoS One 2017; 12: e0183314. 28820906 PMC5562329
  31. [33]Fardoun RZ, Asghar M, Lokhandwala M: Role of oxidative stress in defective renal dopamine D1 receptor-G protein coupling and function in old Fischer 344 rats. Am J Physiol Renal Physiol 2006; 291: F945– F951. 16757732
  32. [34]Jose PA, Soares-da-Silva P, Eisner GM, Felder RA: Dopamine and G protein-coupled receptor kinase 4 in the kidney: role in blood pressure regulation. Biochim Biophys Acta 2010; 1802: 1259– 1267. 20153824 PMC2892632
  33. [35]Banday AA, Marwaha A, Tallam LS, Lokhandwala MF: Tempol reduces oxidative stress, improves insulin sensitivity, decreases renal dopamine D1 receptor hyperphosphorylation, and restores D1 receptor-G-protein coupling and function in obese Zucker rats. Diabetes 2005; 54: 2219– 2226. 15983225
  34. [36]Gildea JJ, Tran HT, Van Sciver RE, Bigler Wang D, Carlson JM, Felder RA: A novel role for c-Myc in G protein-coupled receptor kinase 4 (GRK4) transcriptional regulation in human kidney proximal tubule cells. Hypertension 2013; 61: 1021– 1027. 23509080 PMC3640476
  35. [37]Riva DR, Magalhães CB, Lopes AA, Lanças T, Mauad T, Malm O, Valença SS, Saldiva PH, Faffe DS, Zin WA: Low dose of fine particulate matter (PM2.5) can induce acute oxidative stress, inflammation and pulmonary impairment in healthy mice. Inhal Toxicol 2011; 23(5): 257– 267. 21506876
  36. [39]Cesaroni G, Forastiere F, Stafoggia M, Andersen ZJ, Badaloni C, Beelen R, Caracciolo B, de Faire U, Erbel R, Eriksen KT, Fratiglioni L, Galassi C, Hampel R, Heier M, Hennig F, Hilding A, Hoffmann B, Houthuijs D, Jöckel KH, Korek M, Lanki T, Leander K, Magnusson PK, Migliore E, Ostenson CG, Overvad K, Pedersen NL, J JP, Penell J, Pershagen G, Pyko A, Raaschou-Nielsen O, Ranzi A, Ricceri F, Sacerdote C, Salomaa V, Swart W, Turunen AW, Vineis P, Weinmayr G, Wolf K, de Hoogh K, Hoek G, Brunekreef B, Peters A: Long term exposure to ambient air pollution and incidence of acute coronary events: prospective cohort study and meta-analysis in 11 European cohorts from the ESCAPE Project. BMJ 2014; 348: f7412. 24452269 PMC3898420
  37. [40]Pope CA 3rd, Burnett RT, Thun MJ, Calle EE, Krewski D, Ito K, Thurston GD: Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. JAMA 2002; 287: 1132– 1141. 11879110 PMC4037163
  38. [41]Chen H, Burnett RT, Kwong JC, Villeneuve PJ, Goldberg MS, Brook RD, van Donkelaar A, Jerrett M, Martin RV, Kopp A, Brook JR, Copes R: Spatial association between ambient fine particulate matter and incident hypertension. Circulation 2014; 129: 562– 569. 24190962
  39. [42]Bellavia A, Urch B, Speck M, Brook RD, Scott JA, Albetti B, Behbod B, North M, Valeri L, Bertazzi PA, Silverman F, Gold D, Baccarelli AA: DNA hypomethylation, ambient particulate matter, and increased blood pressure: findings from controlled human exposure experiments. J Am Heart Assoc 2013; 2: e000212. 23782920 PMC3698788
  40. [43]Lin H, Guo Y, Zheng Y, Di Q, Liu T, Xiao J, Li X, Zeng W, Cummings-Vaughn LA, Howard SW, Vaughn MG, Qian ZM, Ma W, Wu F: Long-term effects of ambient PM2.5 on hypertension and blood pressure and attributable risk among older Chinese adults. Hypertension 2017; 69: 806– 812. 28348017 PMC5447129
  41. [44]Chan SH, Van Hee VC, Bergen S, Szpiro AA, DeRoo LA, London SJ, Marshall JD, Kaufman JD, Sandler DP: Long-term air pollution exposure and blood pressure in the sister study. Environ Health Perspect 2015; 123: 951– 958. 25748169 PMC4590742
  42. [45]Upadhyay S, Stoeger T, George L, Schladweiler MC, Kodavanti U, Ganguly K, Schulz H: Ultrafine carbon particle mediated cardiovascular impairment of aged spontaneously hypertensive rats. Part Fibre Toxicol 2014; 11: 36. 25442699 PMC4410795
  43. [46]Wagner JG, Kamal AS, Morishita M, Dvonch JT, Harkema JR, Rohr AC: PM2.5-induced cardiovascular dysregulation in rats is associated with elemental carbon and temperature-resolved carbon subfractions. Part Fibre Toxicol 2014; 11: 25. 24885999 PMC4051889
  44. [47]Wang G, Jiang R, Zhao Z, Song W: Effects of ozone and fine particulate matter (PM(2.5)) on rat system inflammation and cardiac function. Toxicol Lett 2013; 217: 23– 33. 23182954
  45. [48]Gurgueira SA, Lawrence J, Coull B, Murthy GG, González-Flecha B: Rapid increases in the steady-state concentration of reactive oxygen species in the lungs and heart after particulate air pollution inhalation. Environ Health Perspect 2002; 110: 749– 755. PMC1240944 12153754
  46. [49]Sun Q, Yue P, Ying Z, Cardounel AJ, Brook RD, Devlin R, Hwang JS, Zweier JL, Chen LC, Rajagopalan S: Air pollution exposure potentiates hypertension through reactive oxygen species–mediated activation of Rho/ ROCK. Arterioscler Thromb Vasc Biol 2008; 28: 1760– 1766. 18599801 PMC2739008
  47. [50]Bolton JL, Smith SH, Huff NC, Gilmour MI, Foster WM, Auten RL, Bilbo SD: Prenatal air pollution exposure induces neuroinflammation and predisposes offspring to weight gain in adulthood in a sex-specific manner. FASEB J 2012; 26: 4743– 4754. 22815382
  48. [51]Tsai DH, Riediker M, Wuerzner G, Maillard M, Marques-Vidal P, Paccaud F, Vollenweider P, Burnier M, Bochud M: Short-term increase in particulate matter blunts nocturnal blood pressure dipping and daytime urinary sodium excretion. Hypertension 2012; 60: 1061– 1069. 22868388
  49. [52]Rayner B, Ramesar R: The importance of G protein-coupled receptor kinase 4 (GRK4) in pathogenesis of salt sensitivity, salt sensitive hypertension and response to antihypertensive treatment. Int J Mol Sci 2015; 16: 5741– 5749. 25775155 PMC4394502
  50. [53]Cuevas S, Villar VA, Jose PA, Armando I: Renal dopamine receptors, oxidative stress, and hypertension. Int J Mol Sci 2013; 14: 17553– 17572. 23985827 PMC3794741
  51. [54]Usui T, Okada M, Hara Y, Yamawaki H: Death-associated protein kinase 3 mediates vascular inflammation and development of hypertension in spontaneously hypertensive rats. Hypertension 2012; 60: 1031– 1039. 22868392

Cited by

Sorted by citations

Authors
Ye, Z., Lu, X., Deng, Y., Wang, X., Zheng, S., Ren, H., Zhang, M., Chen, T., Jose, P. A., Yang, J., & Zeng, C.
Affiliations
  • Army Medical University (CN)
  • Chongqing Medical University (CN)
ORCID
Venue
Cellular Physiology and Biochemistry
Publisher
S. Karger AG
Published
2018
Volume
46
Issue
1
Pages
148-159
ISSN
  • 1015-8987 (ISSN-L)
  • 1421-9778
DOI
10.1159/000488418
PMC
PMC6437669
OpenAlex
W2795631488
Cited by
34
References
3
Citations by year
2026: 3 · 2025: 7 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 8 · 2020: 2 · 2019: 4 · 2018: 1
FWCI
4.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Cellular Physiology and Biochemistry (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China
  • National Heart, Lung, and Blood Institute (P01HL074940, R37HL023081, R01HL023081)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Air Quality and Health Impacts
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
Keywords
PM2.5, prenatal air pollution exposure, hypertension, GRK4, sodium excretion, diuresis, tempol, c-Myc, prenatal exposure, offspring blood pressure
MeSH terms
Animals, Blood Pressure, Cyclic N-Oxides, Diuresis, Female, Gestational Age, Hypertension, Kidney, Phosphorylation, Pregnancy, Prenatal Exposure Delayed Effects, Spin Labels, Superoxide Dismutase, Down-Regulation, Up-Regulation, Rats, Sprague-Dawley, Receptors, Dopamine D1, Oxidative Stress, Fenoldopam, Rats, Particulate Matter

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review