Matrix metalloproteinases (MMPs) are synthesized in response to diverse stimuli, including cytokines, growth factors, hormones, and oxidative stress. Here we show that the nitric oxide (NO) donor 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA-NO) and NO from murine macrophages transcriptionally regulate MMP-13 expression in vascular endothelial cells (BAEC). The cGMP analog, 8-bromo-cGMP (8-Br-c...

1 Introduction 1 1.1 Pathogenesis and therapy of chronic progressive renal disease 2 1.1.1 Histological and molecular characteristics 2 1.1.2 The central role of TGF-beta in renal fibrosis 2 1.1.3 The sequence of phases leading to progressive renal fibrosis 3 1.1.4 Therapeutic approaches to chronic progressive renal disease 4 1.2 The L-arginine-NO pathway in renal disease 5 1.2.1 Two faces of t...

Effects of low salt (LS) on (pro)renin receptor (PRR) expression are not well established. We hypothesized that LS enhances renal PRR expression via the cGMP-protein kinase G (PKG) signaling pathway. Sprague-Dawley rats were fed a normal-salt (NS) or LS diet associated with intrarenal cortical administration of vehicle (V), the nitric oxide (NO) synthase inhibitor nitro-l-arginine methyl ester ...

Agents that enhance production of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) ameliorate the progression of renal fibrosis. However, the molecular mechanism of this process is not fully understood. We hypothesize that the antifibrotic effects of cGMP and cGMP-dependent kinase I (cGKI) are mediated via regulation of the TGFβ signalling pathway, both via ERK and the Smad-dependent...

Background It has been largely documented the beneficial effects of physical training on the endothelium-derived relaxing response by increasing nitric oxide production and/or its bioavailability to the smooth muscle [1]. L-carnitine (LCar) has been used as important supplement to regulate body composition associated with lipid metabolism. However, no studies exist investigating the effect of L...

Most effects of the messenger molecule nitric oxide (NO) are mediated by cGMP, which is formed by NO-sensitive guanylyl cyclase (GC) and degraded by phosphodiesterases (PDEs). In platelets, NO elicits a spike-like cGMP response and causes a sustained desensitization. Both characteristics have been attributed to PDE5 activation caused by cGMP binding to its regulatory GAF domain. Activation is p...

Background Signaling by intracellular cGMP and cGMP-dependent protein kinase I (cGKI) is the major pathway in vascular smooth muscle, by which endothelial NO regulates vascular tone. The most important targets of cGKI include the myosin-interacting subunit of myosin phosphatase 1, the regulator of G-protein signaling 2, the inositol receptor associated cGKI-substrate, and the BK channel. Recent...