1,721,109 research outputs found
Purinergic receptors and nitric oxide in experimental hypertension: The effects of nitric oxide on P2Y receptor resensitization in spontaneously hypertensive rat mesangial cells
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Transient receptor potential channels, the kidney and hypertension
No full textSmooth muscle cells as well as non-excitable cells express multiple cationic channels with significant permeability to calcium, potassium and sodium. Several of these channels are sensors of calcium store depletion, G-protein coupled receptor activation, membrane stretch, intracellular Ca2+, pH, oxidative stress, phospholipid signals and other factors. A novel family of such channels is encoded by genes homologues of Drosophila TRP (transient receptor potential). Direct evidence exists for roles of TRPC1, TRPC4/5, TRPC6, TRPV2, TRPP1 and TRPP2 in store-operated Ca2+- gating and epithelial cell Ca2+ transport, thus controlling smooth muscle reactivity and at the same time renal homeostasis of divalent cations. Mice deficient in TRPV5 express phenotypic defects amongst which hypercalciuria and impaired bone mineral density. Polycystin 2 (PC2), encoded by the PKD2 gene, is an epithelial transmembrane protein whose mutation is associated to autosomal dominant polycystic kidney disease (ADPKD). PC2 behaves as a TRP-type Ca2+-permeable nonselective cation channel. It is implicated in the transient increase in cytosolic Ca2+ in renal epithelial cells, and may be linked to the activation of subsequent signaling pathways. Recent studies indicate that a PC1-PC2 channel complex is an obligatory novel signaling pathway implicated in the transduction of environmental signals into cellular events. TRP-related ion channels may thus play a role in the pathogenesis of hypertension through direct effects on vascular smooth muscle contraction, renal perfusion/hemodynamics, and the total body balance of divalent cations
Recent perspectives in the mechanisms and therapy of renal sclerosis
No full textChronic renal failure results from progressive sclerosis of injured kidney structures and overload of remnant functioning nephrons in an attempt to compensate for the lost excretory and fluid/solute regulatory capabilities. Key to delaying--or even reversing--the decay of renal function would be a therapy capable of blocking re-nal sclerosis. Therefore, a number of recent studies deal with this issue with a wealth of novel approaches. Considerable success has been achieved in experimental models by applying gene therapy, cell therapy, novel pharmacologic inhibitors of growth factors and matrigenic molecules. While the final step forward to human therapy is not an immediate option, it is likely that the next few years will witness initial trials of novel pharmacologic agents. Along with the already available new drugs suitable to prevent or delay renal transplant rejection or immunologic renal injury, the therapeutic scenario of contemporary nephrology is rapidly evolving. Some major novel findings in the area will be summarized, along with potential implications for human therapy
Uric acid: bystander or culprit in hypertension and progressive renal disease?
No full textIn humans, uric acid is the main urinary metabolite of purines. Serum levels are higher compared with other mammalians. Uric acid is an antioxidant and perhaps helps to control blood pressure during a low Na+ diet through stimulation of the renin-angiotensin system. Serum uric acid is also considered a marker of tubular reabsorption and 'effective' circulating blood volume. Moreover, hyperuricemia seems to be a cofactor in Na+-sensitive hypertension, a marker and possibly itself responsible for microvascular damage through stimulation of the renin angiotensin system, inhibition of endothelial nitric oxide, and proliferative effects on vascular smooth muscle. As fructose-rich diets increase uric acid levels, hyperuricemia may also play a role in the metabolic syndrome, triggering insulin resistance and hypertension. A number of studies on rats rendered hyperuricemic by administration of uricase inhibitors have recently confirmed induction of arterial hypertension and microvascular injury, particularly in the remnant kidney or in cyclosporine-induced renal fibrosis. J Hypertens 26: 2085-2092 (c) 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins
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