Viagra Research Today is a free monthly online journal that collates and summarizes the latest research about Viagra, including details on sildenafil, erectile dysfunction, impotence, side-effects, alternatives.

Negative-Feedback Loop Attenuates Hydrostatic Lung Edema via a cGMP-Dependent Regulation of Transient Receptor Potential Vanilloid 4.

Yin J, Hoffmann J, Kaestle SM, Neye N, Wang L, Baeurle J, Liedtke W, Wu S, Kuppe H, Pries AR, Kuebler WM

Institute of Physiology, Charité-Universitaetsmedizin Berlin, Campus Benjamin Franklin, Arnimallee 22, 14195 Berlin, Germany. wolfgang.kuebler@charite.de.

Although the formation of hydrostatic lung edema is generally attributed to imbalanced Starling forces, recent data show that lung endothelial cells respond to increased vascular pressure and may thus regulate vascular permeability and edema formation. In combining real-time optical imaging of the endothelial Ca(2+) concentration ([Ca(2+)](i)) and NO production with filtration coefficient (K(f)) measurements in the isolated perfused lung, we identified a series of endothelial responses that constitute a negative-feedback loop to protect the microvascular barrier. Elevation of lung microvascular pressure was shown to increase endothelial [Ca(2+)](i) via activation of transient receptor potential vanilloid 4 (TRPV4) channels. The endothelial [Ca(2+)](i) transient increased K(f) via activation of myosin light-chain kinase and simultaneously stimulated NO synthesis. In TRPV4 deficient mice, pressure-induced increases in endothelial [Ca(2+)](i), NO synthesis, and lung wet/dry weight ratio were largely blocked. Endothelial NO formation limited the permeability increase by a cGMP-dependent attenuation of the pressure-induced [Ca(2+)](i) response. Inactivation of TRPV4 channels by cGMP was confirmed by whole-cell patch-clamp of pulmonary microvascular endothelial cells and intravital imaging of endothelial [Ca(2+)](i). Hence, pressure-induced endothelial Ca(2+) influx via TRPV4 channels increases lung vascular permeability yet concomitantly activates an NO-mediated negative-feedback loop that protects the vascular barrier by a cGMP-dependent attenuation of the endothelial [Ca(2+)](i) response. The identification of this novel regulatory pathway gives rise to new treatment strategies, as demonstrated in vivo in rats with acute myocardial infarction in which inhibition of cGMP degradation by the phosphodiesterase 5 inhibitor sildenafil reduced hydrostatic lung edema.

Published 25 April 2008 in Circ Res, 102(8): 966-74.
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Articles on Viagra published 22 April 2008:

Excessive Nitric Oxide Function and Blood Pressure Regulation in Patients With Autonomic Failure.   Hypertension.

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Articles on Viagra published 21 April 2008:

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Articles on Viagra published 18 April 2008:

Role of Smooth Muscle cGMP/cGKI Signaling in Murine Vascular Restenosis.   Arterioscler Thromb Vasc Biol.

Background-Nitric oxide (NO) is of crucial importance for smooth muscle cell (SMC) function and exerts numerous, and sometimes opposing, effects on vascular restenosis. Although cGMP-dependent protein kinase type I (cGKI) is a principal effector of NO, the molecular pathway of vascular NO signaling in restenosis is unclear. The purpose of this study was to examine the functional role of the smooth muscle cGMP/cGKI signaling cascade in restenosis of vessels. METHODS AND RESULTS: Tissue-specific ... [Abstract] [Full-text]

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Articles on Viagra published 17 April 2008:

Yohimbine enhances the effect of sildenafil on erectile process in rats.   Int J Impot Res.

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Articles on Viagra published 16 April 2008:

Protective effects of sildenafil administration on testicular torsion/detorsion damage in rats.   World J Urol, 26(2): 197-202.

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