T-AM

The mathematical model of rat proximal tubule has been extended to include calculation of microvillous torque and to incorporate torque-dependent solute transport in a compliant tubule. The torque calculation follows that of Du Z, Yan Q, Duan Y, Weinbaum S, Weinstein AM, and Wang T (Am J Physiol 290: F289-F296, 2006). In the model calculations, torque-dependent scaling of luminal membrane transporter density [either as an ensemble or just type 3 Na(+)/H(+) exchanger (NHE3) alone] had a relatively small impact on overall Na(+) reabsorption and could produce a lethal derangement of cell volume; coordinated regulation of luminal and peritubular transporters was required to represent the overall impact of luminal flow on Na(+) reabsorption...

In a separate study, we identified PGE2 as a potent inhibitor of TGF-beta1induced epithelial-mesenchymal transition (EMT) in cultured Madin-Darby canine kidney (MDCK) cells (Zhang A, Wang M-H, Dong Z, and Yang T. Am J Physiol Renal Physiol 291: F1323-F1331, 2006). This finding prompted us to examine the roles of other prostanoids: PGD2, PGF(2alpha), PGI2, and thromboxane A2 (TXA2). Treatment with 10 ng/ml TGF-beta1 for 3 days induced EMT as reflected by conversion to the spindle-like morphology, loss of E-cadherin, and activation of alpha-smooth muscle actin (alpha-SMA)...

OBJECTIVE: To investigate the pathophysiological role of the cardiac adrenomedullin (AM) system, including the ligand and amidating activity in the hypertrophied heart in severe hypertension. METHODS: The following four groups were studied: control Wistar Kyoto rats (WKY), spontaneously hypertensive stroke-prone rats (SHR-SP), 8 weeks captopril-treated SHR-SP, and 8 weeks trichlormethiazide-treated SHR-SP. AM precursor was converted to inactive glycine-extended AM (AM-Gly) and subsequently AM-Gly was converted to active mature AM (AM-m) by enzymatic amidation...

Animals decerebrated at the precollicular-premammillary body level exhibit spontaneous locomotion without any artificial stimulation. Our laboratory reported that the cardiovascular and autonomic responses at the onset of spontaneous locomotor events are evoked by central command, generated from the caudal diencephalon and the brain stem (Matsukawa K, Murata J, and Wada T. Am J Physiol Heart Circ Physiol 275: H1115-H1121, 1998). In this study, we examined whether central command and/or a reflex resulting from muscle afferents modulates arterial baroreflex function using a decerebrate cat model...

To elucidate the dynamical mechanisms of the sinoatrial (SA) node pacemaker activity, we investigated the roles of L-type Ca2+ (ICa,L) and delayed-rectifier K+ (IKr) currents in pacemaking by stability and bifurcation analyses of our rabbit SA node model (Kurata Y, Hisatome I, Imanishi S, and Shibamoto T. Am J Physiol Heart Circ Physiol 283: H2074-H2101, 2002). Equilibrium points (EPs), periodic orbits, stability of EPs, and Hopf bifurcation points were calculated as functions of conductance or gating time constants of the currents for constructing bifurcation diagrams...

OBJECT: We investigated the pathophysiological role of the cardiac adrenomedullin (AM) system, including the ligand, receptor and amidating activity in the hypertrophied heart in severe hypertension. METHOD: We studied the following four groups: control Wistar-Kyoto rats (WKY), spontaneously hypertensive stroke-prone rats (SHR-SP), 8 weeks captopril-treated SHR-SP, and 8 weeks trichlormethiazide-treated SHR-SP. AM precursor is converted to inactive glycine-extended AM (AM-Gly) and subsequently AM-Gly is converted to active mature AM (AM-m) by enzymatic amidation...

Controversy exists as to the origin of plasma adrenomedullin (AM). To elucidate the source of plasma AM, we measured two molecular forms of AM, an active form of mature AM (AM-m) and an intermediate inactive form of glycine-extended AM (AM-Gly), by immunoradiometric assay using specific kits in two female patients with pheochromocytoma before and 3 weeks after surgery. We also measured plasma AM-m, AM-Gly, and AM-T (AM-m + AM-Gly) levels, in addition to plasma epinephrine (E) and norepinephrine (NE) levels, in bilateral adrenal veins of one patient...

Experimental studies have demonstrated that adrenomedullin (AM) has a positive inotropic action and exerts inhibitory effects against ventricular remodelling as an autocrine and paracrine factor. However, there is no clinical evidence for AM acting as a local regulator in the human heart. We measured the levels of various molecular forms of AM, i.e. an active form of mature AM (AM-m), an intermediate inactive form of glycine-extended AM (AM-Gly) and total AM (AM-T=AM-m+AM-Gly), in plasma and pericardial fluid using our newly developed immunoradiometric assay in consecutive 67 patients undergoing coronary artery bypass graft surgery...

The purpose of this study is to develop a numerical model that simulates acid-base transport in rat distal tubule. We have previously reported a model that deals with transport of Na(+), K(+), Cl(-), and water in this nephron segment (Chang H and Fujita T. Am J Physiol Renal Physiol 276: F931-F951, 1999). In this study, we extend our previous model by incorporating buffer systems, new cell types, and new transport mechanisms. Specifically, the model incorporates bicarbonate, ammonium, and phosphate buffer systems; has cell types corresponding to intercalated cells; and includes the Na/H exchanger, H-ATPase, and anion exchanger...

OBJECTIVES: Human adrenomedullin precursor is converted to glycine-extended adrenomedullin (AM-Gly), an intermediate inactive form of adrenomedullin. Subsequently, AM-Gly is converted to active form of mature adrenomedullin (AM-m). The aim of the present study was to investigate (i) whether sex or age influences plasma and urinary AM-m and AM-Gly levels in normal subjects; (ii) the daytime variability of plasma AM-m and AM-Gly levels in normal subjects; (iii) AM-m and AM-Gly levels and its ratio in plasma and urine in normal subjects, individuals with essential hypertension (HT), and chronic renal failure (CRF); and (iv) the ratio of AM-m and AM-total (T) in plasma of various veins and aorta...

Adrenomedullin (AM) has vasodilatory, diuretic and natriuretic actions. Two molecular forms of AM circulate in human plasma: an active, mature form of AM (AM-m) and an intermediate, inactive, glycine-extended form of AM (AM-Gly). In the present study we investigated the pathophysiological significance of the two molecular forms of AM in plasma and urine in patients with acute myocardial infarction. We serially measured venous and arterial plasma levels and urinary excretion of AM-m, AM-Gly and total AM (Am-T; =AM-m+AM-Gly) over 2 weeks using our recently developed immunoradiometric assay in 26 consecutive patients with acute myocardial infarction and in age-matched normal controls, and studied the relationships between AM levels and clinical parameters...

Adrenomedullin (AM), a novel hypotensive peptide, preferentially dilates pulmonary vessels rather than systemic vessels. This suggests the possibility that AM is a circulating hormone which participates in regulation of the pulmonary circulation. A recent study revealed that two molecular forms of AM, i.e. a mature, active form of AM (AM-m) and an intermediate, inactive, glycine-extended form of AM (AM-Gly), circulate in human plasma. In the present study we investigated the production and clearance sites and pathophysiological significance of the two molecular forms of AM in the pulmonary circulation in patients with mitral stenosis...

Human adrenomedullin (AM) precursor is converted to glycine-extended AM (AM-Gly), an inactive intermediate form of AM. Subsequently, AM-Gly is converted to active mature AM (AM-m) by enzymatic amidation. A recent study showed that two molecular forms of adrenomedullin (AM) are present in human plasma. In this study we investigated the production and clearance sites of two molecular forms of adrenomedullin in humans. We measured plasma levels of AM-m and AM-Total (T) (AM-m+AM-Gly) by immunoradiometric assay and calculated plasma levels of AM-Gly in blood samples taken from various sites during cardiac catheterization in patients with ischemic heart disease...

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Volume oscillations of liver mitochondria resulting from valinomycin induced K+ transport, may be represented by the equation At/Am = C'.exp(-beta t).sin(omega 1t+ psi) where At is the oscillation amplitude at time t; Am, the maximal amplitude; beta, the damping coefficient, omega 1 the oscillation frequency, and C' and psi, constants. The kinetic parameters beta and omega 1 increased as a function of valinomycin concentration. Measurement of beta and omega 1 for mitochondria from normal rats (A); diabetic rats (B), and normal rats fed corn oil or lard-supplemented diets (C and D, respectively), yielded an increase in beta (P less than 0...