| Full text | |
| Author(s): |
Loiola, Rodrigo A.
[1]
;
Torres, Tathiany C.
[1]
;
Landgraf, Richardt G.
[1]
;
Pesquero, Joao Bosco
[2]
;
Fernandes, Liliam
[1]
Total Authors: 5
|
| Affiliation: | [1] Univ Fed Sao Paulo, Lab Inflamacao & Farmacol Vasc, Inst Ciencias Ambientais Quim & Farmaceut, BR-09913030 Diadema, SP - Brazil
[2] Univ Fed Sao Paulo, Dept Biofis, BR-04039032 Sao Paulo, SP - Brazil
Total Affiliations: 2
|
| Document type: | Journal article |
| Source: | INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS; v. 21, n. 3, p. 375-382, SEP 2015. |
| Web of Science Citations: | 1 |
| Abstract | |
Kinins are vasoactive peptides involved in endothelial function and vascular tonus. The present study determined the influence of the kinin B-1 receptor subtype on endothelial nitric oxide (NO) metabolism by using primary cultured cells obtained from B-1 knockout (B (1) (-/-) ) and Wild Type (WT) mice. By using specific fluorescent dyes, NO and superoxide anion ( (a (TM))) production was determined in absence or presence of ascorbate or tetrahydrobiopterin (BH4). The activity of the enzyme superoxide dismutase (SOD) was determined by immune enzyme assay, and endothelial NOS (eNOS) activation was analyzed through expression of phospho-eNOS (p-eNOS, Ser1177) by western blot. The NO release {[}quantified by densitometry and expressed as arbitrary units (a.u.)] was markedly reduced in B (1) (-/-) (35.8 +/- A 3.1{*} a.u.) when compared to WT cells (66.9 +/- A 3.2 a.u.); this impaired response was reversed by ascorbate (101.8 +/- A 6.0 a.u.) and BH4 (54.3 +/- A 1.7 a.u.). B (1) (-/-) cells showed a marked increase in (a (TM)) production (77.1 +/- A 2.5{*} a.u.) versus WT (29.3 +/- A 6.9 a.u.), which was reversed by ascorbate (35.3 +/- A 6.4 a.u.), but not by BH4. SOD activity was similar between groups, and B (1) (-/-) cells presented a significant reduction in the expression of p-eNOS. In conclusion, the reduced NO availability detected in B (1) (-/-) cells appears to be related to a recurrent process involving BH4 oxidation, NOS uncoupling and further enhancement of NOS-derived (a (TM)). B-1 receptor deletion also impairs the phosphorylation of eNOS at the Ser1177 residue, contributing to the deficient NO production at the endothelial level. (AU) | |
| FAPESP's process: | 14/18760-4 - Venous endothelial factors: influence of angiotensin II and endothelin-1 |
| Grantee: | Liliam Fernandes |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 08/06676-8 - Cellular and molecular biology of the kallikrein-kinin and renin-angiotensin systems |
| Grantee: | João Bosco Pesquero |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 10/01404-0 - In vivo and in vitro studies of the leptin role in different models of lung inflammation: inflammatory mediators and signaling airways participation |
| Grantee: | Richardt Gama Landgraf |
| Support Opportunities: | Research Grants - Young Investigators Grants |