1. C-type natriuretic peptide-induced relaxation through cGMP-dependent protein kinase and SERCA activation is impaired in two kidney-one clip rat aorta.
- Author
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Pernomian L, do Prado AF, Silva BR, de Paula TD, Grando MD, and Bendhack LM
- Subjects
- Animals, Blood Pressure drug effects, Cyclic GMP metabolism, Cyclic GMP-Dependent Protein Kinases metabolism, Endothelial Cells metabolism, Endothelium, Vascular metabolism, Guanylate Cyclase metabolism, Hypertension physiopathology, Kidney metabolism, Male, Natriuretic Peptide, C-Type metabolism, Natriuretic Peptides metabolism, Natriuretic Peptides pharmacology, Nitric Oxide metabolism, Nitric Oxide Synthase metabolism, Rats, Rats, Wistar, Surgical Instruments, Vasodilation physiology, Natriuretic Peptide, C-Type pharmacology, Sarcoplasmic Reticulum Calcium-Transporting ATPases metabolism, Vasodilation drug effects
- Abstract
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 Ca
2+ -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., (Copyright © 2021 Elsevier Inc. All rights reserved.)- Published
- 2021
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