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Exaggerated production of nitric oxide (NO) and increases in inducible NO-synthase mRNA levels induced by the pro-inflammatory cytokine interleukin-1beta in vascular smooth muscle cells of elderly rats.
Exp Gerontol 2004; 39(3):387-94EG

Abstract

Nitric oxide (NO) is produced at high levels by inducible nitric oxide synthase (iNOS) during inflammation and other pathological conditions, contributing to development of cardiovascular diseases. The present study determined if aging affects the ability of interleukin-1beta (IL-1beta), a pro-inflammatory cytokine, to induce increased NO production (assessed by Griess reaction) and iNOS mRNA levels (assessed by RT-PCR/agarose gel electrophoresis) in vascular smooth muscle cells (VSMCs) from young (3-month-old) and elderly (20-22-month-old) rats. The VSMCs cells were used only in early passages (passages 0 and 1) to avoid phenotypic modulation. To uncover subtle differences in basal iNOS mRNA levels in VSMCs of young and elderly rats, RT-PCR products were also analyzed by a new ultrasensitive technique using capillary electrophoresis with laser-induced fluorescence detector (CE-LIF). IL-1beta (5 ng/ml) significantly (P < 0.05) increased NO production 3.7-fold in elderly female VSMCs and 6.7-fold in elderly male VSMCs, but had no detectable effect in young female and male VSMCs. Basal iNOS mRNA levels (assessed by RT-PCR/CE-LIF) were dramatically higher in VSMCs of elderly male rats compared to young ones. In general, VSMCs of elderly rats showed much greater sensitively to iNOS-inducing actions of IL-1beta. These data give new insight into effects of aging on iNOS expression in VSMCs, showing dramatic increases in both basal and stimulated iNOS mRNA levels, which may contribute to the development of vascular diseases in the elderly.

Authors+Show Affiliations

Department of Physiology, Faculty of Medicine, Epithelial Cell Biology Research Center, and The Center for Gerontology and Geriatrics, The Chinese University of Hong Kong, Room 507, BMSB, Shatin, New Territories, Hong Kong, China.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15036398

Citation

Chan, Gabriel H H., and Ronald R. Fiscus. "Exaggerated Production of Nitric Oxide (NO) and Increases in Inducible NO-synthase mRNA Levels Induced By the Pro-inflammatory Cytokine Interleukin-1beta in Vascular Smooth Muscle Cells of Elderly Rats." Experimental Gerontology, vol. 39, no. 3, 2004, pp. 387-94.
Chan GH, Fiscus RR. Exaggerated production of nitric oxide (NO) and increases in inducible NO-synthase mRNA levels induced by the pro-inflammatory cytokine interleukin-1beta in vascular smooth muscle cells of elderly rats. Exp Gerontol. 2004;39(3):387-94.
Chan, G. H., & Fiscus, R. R. (2004). Exaggerated production of nitric oxide (NO) and increases in inducible NO-synthase mRNA levels induced by the pro-inflammatory cytokine interleukin-1beta in vascular smooth muscle cells of elderly rats. Experimental Gerontology, 39(3), pp. 387-94.
Chan GH, Fiscus RR. Exaggerated Production of Nitric Oxide (NO) and Increases in Inducible NO-synthase mRNA Levels Induced By the Pro-inflammatory Cytokine Interleukin-1beta in Vascular Smooth Muscle Cells of Elderly Rats. Exp Gerontol. 2004;39(3):387-94. PubMed PMID: 15036398.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exaggerated production of nitric oxide (NO) and increases in inducible NO-synthase mRNA levels induced by the pro-inflammatory cytokine interleukin-1beta in vascular smooth muscle cells of elderly rats. AU - Chan,Gabriel H H, AU - Fiscus,Ronald R, PY - 2003/09/18/received PY - 2003/12/22/revised PY - 2004/01/13/accepted PY - 2004/3/24/pubmed PY - 2004/7/21/medline PY - 2004/3/24/entrez SP - 387 EP - 94 JF - Experimental gerontology JO - Exp. Gerontol. VL - 39 IS - 3 N2 - Nitric oxide (NO) is produced at high levels by inducible nitric oxide synthase (iNOS) during inflammation and other pathological conditions, contributing to development of cardiovascular diseases. The present study determined if aging affects the ability of interleukin-1beta (IL-1beta), a pro-inflammatory cytokine, to induce increased NO production (assessed by Griess reaction) and iNOS mRNA levels (assessed by RT-PCR/agarose gel electrophoresis) in vascular smooth muscle cells (VSMCs) from young (3-month-old) and elderly (20-22-month-old) rats. The VSMCs cells were used only in early passages (passages 0 and 1) to avoid phenotypic modulation. To uncover subtle differences in basal iNOS mRNA levels in VSMCs of young and elderly rats, RT-PCR products were also analyzed by a new ultrasensitive technique using capillary electrophoresis with laser-induced fluorescence detector (CE-LIF). IL-1beta (5 ng/ml) significantly (P < 0.05) increased NO production 3.7-fold in elderly female VSMCs and 6.7-fold in elderly male VSMCs, but had no detectable effect in young female and male VSMCs. Basal iNOS mRNA levels (assessed by RT-PCR/CE-LIF) were dramatically higher in VSMCs of elderly male rats compared to young ones. In general, VSMCs of elderly rats showed much greater sensitively to iNOS-inducing actions of IL-1beta. These data give new insight into effects of aging on iNOS expression in VSMCs, showing dramatic increases in both basal and stimulated iNOS mRNA levels, which may contribute to the development of vascular diseases in the elderly. SN - 0531-5565 UR - https://www.unboundmedicine.com/medline/citation/15036398/Exaggerated_production_of_nitric_oxide__NO__and_increases_in_inducible_NO_synthase_mRNA_levels_induced_by_the_pro_inflammatory_cytokine_interleukin_1beta_in_vascular_smooth_muscle_cells_of_elderly_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S053155650400018X DB - PRIME DP - Unbound Medicine ER -