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Natriuretic peptides (NPs) and their receptors (NPRs) are expressed in the heart, but their effects on myocyte function are poorly understood. Because NPRs are coupled to synthesis of cGMP, an activator of the sarcolemmal [Na.sup.+]-[K.sup.+] pump, we examined whether atrial natriuretic peptide (ANP) regulates the pump. We voltage clamped rabbit ventricular myocytes and identified electrogenic [Na.sup.+]-[K.sup.+] pump current (arising from the 3:2 [Na.sup.+]:[K.sup.+] exchange and normalized for membrane capacitance) as the shift in membrane current induced by 100 [micro]mol/1 ouabain. Ten nanomoles per liter ANP stimulated the [Na.sup.+]-[K.sup.+] pump when the intracellular compartment was perfused with pipette solutions containing 10 mmol/1 [Na.sup.+] but had no effect when the pump was at near maximal activation with 80 mmol/1 [Na.sup.+] in the pipette solution. Stimulation was abolished by inhibition of cGMP-activated protein kinase with KT-5823, nitric oxide (NO)-activated guanylyl cyclase with 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ), or NO synthase with [N.sup.G]-nitro-L-arginine methyl ester (L-NAME). Since synthesis of cGMP by NPR-A and NPR-B is not NO dependent or ODQ sensitive, we exposed myocytes to AP-811, a highly selective ligand for the NPR-C 'clearance' receptor. It abolished ANP-induced pump stimulation. Conversely, the selective NPR-C agonist ANP(423) reproduced stimulation. The stimulation was blocked by L-NAME. To examine NO production in response to ANP(4-23), we loaded myocytes with the NO-sensitive fluorescent dye diacetylated diaminofluorescein-2 and examined them by confocal microscopy. ANP(4-23) induced a significant increase in fluorescence, which was abolished by L-NAME. We conclude that NPs stimulate the [Na.sup.+]-[K.sup.+] pump via an NPR-C and NO-dependent pathway. cyclic guanosine 3',5'-cyclic monophosphate-activated kinase; nitric oxide synthase; congestive cardiac failure; atrial natriuretic peptide

Pharmacological delivery of nitric oxide (NO) stimulates the cardiac [Na.sup.+]-[K.sup.+] pump. However, effects of NO synthesized by NO synthase (NOS) often differ from the effects of NO delivered pharmacologically. In addition, NOS can become 'uncoupled' and preferentially synthesize [O.sub.2*.sup.-], which often has opposing effects to NO. We tested the hypothesis that NOS-synthesized NO stimulates [Na.sup.+]-[K.sup.+] pump activity, and uncoupling of NOS inhibits it. To image NO, we loaded isolated rabbit cardiac myocytes with 4,5-diaminofluorescein-2 diacetate (DAF-2 DA) and measured fluorescence with confocal microscopy. L-Arginine (L-Arg; 500 [micro]mol/l) increased DAF-2 DA fluorescence by 51% compared with control (n = 8; P < 0.05). We used the whole cell patch-clamp technique to measure electrogenic [Na.sup.+]-[K.sup.+] pump current (Ip). Mean [I.sub.p] of 0.35 [+ or -] 0.03 pA/pF (n = 44) was increased to 0.48 [+ or -] 0.03 pA/pF (n = 7, P < 0.05) by 10 [micro]mol/l L-Arg in pipette solutions. This increase was abolished by NOS inhibition with radicicol or by NO-activated guanylyl cyclase inhibition with IH-[l,2,4]oxadiazole[4,3-a]quinoxalin-l-one. We next examined the effect of uncoupling NOS using paraquat. Paraquat (1 mmol/l) induced a 51% increase in the fluorescence intensity of [O.sub.2*.-]-sensitive dye dihydroethidium compared with control (n = 9; P < 0.05). To examine the functional effects of uncoupling, we measured [I.sub.p] with 100 [micro]mol/1 paraquat included in patch pipette solutions. This decreased [I.sub.p] to 0.28 [+ or -] 0.03 pA/pF (n = 12; P < 0.001). The paraquat-induced pump inhibition was abolished by superoxide dismutase (in pipette solutions). We conclude that NOS-mediated NO synthesis stimulates the [Na.sup.+]-[K.sup.+] pump, whereas uncoupling of NOS causes [O.sub.2*.-]-mediated pump inhibition. myocyte; nitric oxide; superoxide: oxidative stress

A study was conducted to analyze mechanisms of Na+-K+ pump regulation in cardiac myocytes during hyposmolar swelling. Single ventricular myocytes were determined from New Zealand White rabbits. Experimental results indicated that swelling-induced pump stimulation correlates with the activation of tyrosine kinase, phosphatidylinositol 3-kinase and a serine/threonine protein phosphatase.

Discusses a review of the case records on 48 patients aged 60 years and older with a diagnosis of acute bacterial meningitis. Most common symptoms; Emphasis on clinical and biochemical features, the microbiology; Question of whether simple clinical symptoms and signs can be used as predictors of prognosis; Study of medical departments in Jutland, Denmark; Difficulty of diagnosis; More.