C-type natriuretic peptide-induced relaxation through cGMP-dependent protein kinase and SERCA activation is impaired in two kidney-one clip rat aorta

Autor(es)

Pernomian, Laena ^[1] ; do Prado, Alejandro Ferraz ^{[1, 2]} ; Silva, Bruno Rodrigues ^{[1, 3]} ; de Paula, Tiago Dal-Cin ^{[1, 3]} ; Grando, Marcella Daruge ^[3] ; Bendhack, Lusiane Maria ^[3]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Fed Univ Para, Inst Biol Sci, Lab Struct Biol, Belem, Para - Brazil

^[3] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, Dept Phys & Chem, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Life Sciences; v. 272, MAY 1 2021.
• Citações Web of Science: 0

Resumo

Aims: Hypertension underlies endothelial dysfunction, and activation of vasorelaxation signaling with low dependence on nitric oxide (NO) represents a good alternative for vascular modulation. C-type natriuretic peptide (CNP) causes relaxation by increasing cyclic guanosine 3',5'-monophosphate (cGMP) or Gi-protein activation through its natriuretic peptide receptor-B or -C, respectively. We have hypothesized that CNP could exerts its effects and could overcome endothelial dysfunction in two kidney-one clip (2K-1C) hypertensive rat aorta. Here, we investigate the intracellular signaling involved in CNP effects in hypertension. Materials and methods: The 2K-1C hypertension was induced in male Wistar rats (200 g). CNP-induced vascular relaxation and cGMP production were investigated in rat thoracic aortas. The natriuretic peptide receptor-B and -C localization was evaluated by immunofluorescence. Calcium mobilization was assessed in endothelial cells from rat aortas. Key findings: CNP induced similar relaxation in normotensive and 2K-1C hypertensive rat aortas, which increased after endothelium removal. CNP-induced relaxation involved natriuretic peptide receptor-B and -C activation in 2K-1C rats. Nitric oxide synthase (NOS) and soluble guanylyl cyclase (sGC) counter-regulated CNP-particulate GC (pGC) activation in aortas. CNP reduced endothelial calcium and increased cGMP production, which was lower in 2K-1C. CNP-induced cGMP-dependent protein kinase (PKG) and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) activation was impaired in 2K-1C rat aorta. Significance: Our results indicated CNP triggered relaxation through its natriuretic peptide receptor-B and -C in 2K-1C rat aortas, and that CNP-induced relaxation overcomes endothelial dysfunction in hypertension. In addition, NOS and sGC activities counter-regulate CNP-pGC activation to induce vascular relaxation. (AU)

• Processo FAPESP: 11/11205-7 - Modulação promovida pelo peptídeo natriurético tipo C (CNP) sobre a resposta contrátil induzida pela fenilefrina em aorta torácica e artérias mesentéricas de resistência isoladas de ratos submetidos ao choque séptico
• Beneficiário: Laena Pernomian
• Modalidade de apoio: Bolsas no Brasil - Doutorado