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

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.

The Role of Glycocalyx and Caveolae in Vascular Homeostasis and Diseases.

This review highlights recent findings about the role that endothelial glycocalyx and caveolae play in vascular homeostasis. We describe the structure, synthesis, and function of glycocalyx and caveolae in vascular cells under physiological and pathophysiological conditions. Special focus will be given in glycocalyx and caveolae that are associated with impaired production of nitric oxide (NO) and generation of reactive oxygen species (ROS). Such alterations could contribute to the development of cardiovascular diseases, such as atherosclerosis, and hypertension.