Biomaterial Database

Nitric oxide stimulates guanylate cyclase and regulates sodium transport in rabbit proximal tubule. 1996

A Roczniak, and K D Burns

Department of Medicine, University of Ottawa, Ontario, Canada.

The proximal tubule contains the target for nitric oxide (NO), soluble guanylate cyclase, and has the capacity for NO production. Inhibition of renal NO synthesis reduces fractional excretion of lithium, suggesting an inhibitory effect of NO on proximal tubule Na+ transport. The present studies determined direct effects of donors of NO in rabbit proximal tubule. In both freshly isolated proximal tubule segments and in primary cultures of proximal tubule cells, sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) caused dose-dependent increases in guanosine 3',5'-cyclic monophosphate (cGMP). SNAP was more potent than SNP in stimulating cGMP; this was associated with an enhanced production of nitrite, the stable end-product of NO. In rabbit proximal tubule cells, SNP or SNAP (10(-3) M) significantly inhibited the activity of the apical Na+/H+ exchanger, determined by assay of amiloride-sensitive 22Na+ uptake (% inhibition: SNP, 34.90 +/- 5.52%, P < 0.001; SNAP, 30.77 +/- 8.20%, P < 0.002). To determine the role of cGMP in mediating these effects, proximal tubule cells were incubated with the membrane-permeable analogue, 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP). Na+/H+ exchange was significantly inhibited by 8-BrcGMP (10(3)M) (% inhibition: 32.40 +/- 9.06%: P < 0.05). The inhibitor of soluble guanylate cyclase, LY-83583, caused partial inhibition of SNP-stimulated cGMP generation and partly blocked the inhibitory effect of SNP on Na+/H+ exchange. Protein kinase A (PKA) activity was not stimulated by SNP, indicating that potential cross-activation of PKA by cGMP did not mediate the effects of NO donors. These data indicate that NO stimulates soluble guanylate cyclase in rabbit proximal tubule and causes inhibition of Na-/H+ exchange. This is at least partly mediated by generation of cGMP. We conclude that NO is an important autocrine or paracrine factor directly regulating Na+ transport in the proximal tubule.

UI	MeSH Term	Description	Entries
D007687	Kidney Tubules, Proximal	The renal tubule portion that extends from the BOWMAN CAPSULE in the KIDNEY CORTEX into the KIDNEY MEDULLA. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the U-shaped LOOP OF HENLE.	Proximal Kidney Tubule,Proximal Renal Tubule,Kidney Tubule, Proximal,Proximal Kidney Tubules,Proximal Renal Tubules,Renal Tubule, Proximal,Renal Tubules, Proximal,Tubule, Proximal Kidney,Tubule, Proximal Renal,Tubules, Proximal Kidney,Tubules, Proximal Renal
D009569	Nitric Oxide	A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.	Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D009599	Nitroprusside	A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.	Nitroferricyanide,Sodium Nitroprusside,Cyanonitrosylferrate,Ketostix,Naniprus,Nipride,Nipruton,Nitriate,Nitropress,Nitroprussiat Fides,Nitroprusside, Disodium Salt,Nitroprusside, Disodium Salt, Dihydrate,Disodium Salt Nitroprusside,Nitroprusside, Sodium
D010396	Penicillamine	3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease.	Dimethylcysteine,Mercaptovaline,beta,beta-Dimethylcysteine,Copper Penicillaminate,Cuprenil,Cuprimine,D-3-Mercaptovaline,D-Penicillamine,Metalcaptase,D 3 Mercaptovaline,D Penicillamine,Penicillaminate, Copper,beta,beta Dimethylcysteine
D011817	Rabbits	A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes.	Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D002352	Carrier Proteins	Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes.	Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004789	Enzyme Activation	Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.	Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D005260	Female		Females
D006152	Cyclic GMP	Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)	Guanosine Cyclic 3',5'-Monophosphate,Guanosine Cyclic 3,5 Monophosphate,Guanosine Cyclic Monophosphate,Guanosine Cyclic-3',5'-Monophosphate,3',5'-Monophosphate, Guanosine Cyclic,Cyclic 3',5'-Monophosphate, Guanosine,Cyclic Monophosphate, Guanosine,Cyclic-3',5'-Monophosphate, Guanosine,GMP, Cyclic,Guanosine Cyclic 3',5' Monophosphate,Monophosphate, Guanosine Cyclic