NON-UNIQUELY SOLVABLE NETWORK MODELS

Many methods are known from the literature to perform the analysis of a linear electrical circuit by its nullator norator pairs model. A procedure based on such a method is very elegant from the aspect of the network theory. If a linear electrical circuit is uniquely solvable, then its nullator norator pairs model is also solvable but not necessarily uniquely. The procedure mentioned above can be applied only if the model has a unique solution. For example, if the electrical circuit contains a two-port network part without a common vertex, then its model cannot be calculated in the previous manner, in general. The present paper releases the limit of this procedure. First the author deals with non-uniquely solvable nullator norator pairs networks of different sort, and selects those networks which occur most often during the modelling. After defining the notion of the quasiregular network its basic properties are introduced. Further properties are summarized in two theorems, which enable the calculation of quasiregular networks, such that this calculation is traced back to uniquely solvable nullator norator pairs networks. Finally, an example is given for the application of the author's procedure

Difference between male and female rats in vasopressor response to arginine vasopressin

A study was carried out how the sexual difference influences the increase in blood pressure (BP) induced by arginine vasopressin (AVP), and how the binding characteristics of 3H-labelled AVP on membranes prepared from the vascular bed were affected. After the administration of various doses of AVP, a significantly higher BP increase was observed in male rats than in females. The vasopressor effect of AVP was reduced in males following orchidectomy or administration of the antiandrogen cyproterone acetate. The vasopressin (VP) antagonist d(CH2)5Tyr(Me)AVP diminished the BP response to AVP in both sexes. The plasma AVP level was found to be much higher in males than in females, but it was decreased to the level of females after orchidectomy. The density of AVP-binding sites in the aorta membrane preparation was smaller in females, and in orchidectomized or cyproterone acetate-treated male rats than in the control males. The results demonstrate that testosterone upregulates the number of AVP-binding sites, leading to an increase in the pressor response to AVP in the rat vascular bed

Anti-Inflammatory Effect of Recreational Exercise in TNBS-Induced Colitis in Rats: Role of NOS/HO/MPO System

There are opposite views in the available literature: Whether physical exercise has a protective effect or not on the onset of inflammatory bowel disease (IBD). Therefore, we investigated the effects of recreational physical exercise before the induction of colitis. After 6 weeks of voluntary physical activity (running wheel), male Wistar rats were treated with TNBS (10 mg). 72 hrs after trinitrobenzene sulphonic acid (TNBS) challenge we measured colonic gene (TNF-, IL-1 , CXCL1 and IL-10) and protein (TNF-) expressions of various inflammatory mediators and enzyme activities of heme oxygenase (HO), nitric oxide synthase (NOS), and myeloperoxidase (MPO) enzymes. Wheel running significantly increased the activities of HO, constitutive NOS (cNOS) isoform. Furthermore, 6 weeks of running significantly decreased TNBS-induced inflammatory markers, including extent of lesions, severity of mucosal damage, and gene expression of IL-1 , CXCL1, and MPO activity, while IL-10 gene expression and cNOS activity were increased. iNOS activity decreased and the activity of HO enzyme increased, but not significantly, compared to the sedentary TNBS-treated group. In conclusion, recreational physical exercise can play an anti-inflammatory role by downregulating the gene expression of proinflammatory mediators, inducing anti-inflammatory mediators, and modulating the activities of HO and NOS enzymes in a rat model of colitis

In vivo MRI and ex vivo histological assessment of the cardioprotection induced by ischemic preconditioning, postconditioning and remote conditioning in a closed-chest porcine model of reperfused acute myocardial infarction: importance of microvasculature

BACKGROUND: Cardioprotective value of ischemic post- (IPostC), remote (RIC) conditioning in acute myocardial infarction (AMI) is unclear in clinical trials. To evaluate cardioprotection, most translational animal studies and clinical trials utilize necrotic tissue referred to the area at risk (AAR) by magnetic resonance imaging (MRI). However, determination of AAR by MRI' may not be accurate, since MRI-indices of microvascular damage, i.e., myocardial edema and microvascular obstruction (MVO), may be affected by cardioprotection independently from myocardial necrosis. Therefore, we assessed the effect of IPostC, RIC conditioning and ischemic preconditioning (IPreC; positive control) on myocardial necrosis, edema and MVO in a clinically relevant, closed-chest pig model of AMI. METHODS AND RESULTS: Acute myocardial infarction was induced by a 90-min balloon occlusion of the left anterior descending coronary artery (LAD) in domestic juvenile female pigs. IPostC (6 x 30 s ischemia/reperfusion after 90-min occlusion) and RIC (4 x 5 min hind limb ischemia/reperfusion during 90-min LAD occlusion) did not reduce myocardial necrosis as assessed by late gadolinium enhancement 3 days after reperfusion and by ex vivo triphenyltetrazolium chloride staining 3 h after reperfusion, however, the positive control, IPreC (3 x 5 min ischemia/reperfusion before 90-min LAD occlusion) did. IPostC and RIC attenuated myocardial edema as measured by cardiac T2-weighted MRI 3 days after reperfusion, however, AAR measured by Evans blue staining was not different among groups, which confirms that myocardial edema is not a measure of AAR, IPostC and IPreC but not RIC decreased MVO. CONCLUSION: We conclude that IPostC and RIC interventions may protect the coronary microvasculature even without reducing myocardial necrosis

Lack of interaction of vasopressin with its antisense peptides: a functional and immunological study

The peptide encoded in the 5' to 3' direction by rat vasopressin complementary RNA, rat PVA (H-Ser-Ser-Trp-Ala-Val-Leu-Glu-Val-Ala- OH) and the corresponding bovine PVA (H-Ala-Pro-Trp-Ala-Val-Leu-Glu-Val-Ala-OH) were investigated with respect to their interaction with [8-arginine] vasopressin (AVP) and V2 vasopressin receptor binding and function. Rat or bovine PVA did neither affect the binding of the hormone to the V2 receptor of bovine kidney membranes and LLC-PK1 pig kidney cells nor influence the AVP-induced cAMP-production in LLC-PK1 cells. Rat PVA was further investigated by the use of vasopressin-specific polyclonal and monoclonal antibodies with different affinity and epitope specificity. Consistent with receptor binding studies no inhibition of [3H]AVP-binding in fluid- or solid-phase antibody binding tests after preincubation with PVA was found. Direct interaction of rat PVA and [3H]AVP measured on solid surface was not observed in contrast to specific binding of the hormone with NP II and antibodies. In our study no evidence for an interaction of AVP and its antisense peptides was found

Oxytocin induced cAMP-dependent protein kinase activation and urokinase-type plasminogen activator production in LLC-PK₁ renal epithelial cells is mediated by the vasopressin V₂-receptor

Using a variety of peptide analogues of oxytocin (OT) and Arg8-vasopressin (AVP), OT-mediated induction of urokinase-type plasminogen activator (uPA) was examined in LLC-PK1 renal epithelial cells, which possess distinct high-affinity receptors of both the OT- and vasopressin renal (V2-) types. OT or OT-receptor specific agonists induced concentration-dependent cAMP synthesis, activation of the cAMP-dependent protein kinase (cAMP-PK) and uPA production consistent with their respective binding affinities for the V2- and not the OT-receptor. OT-mediated uPA induction could be inhibited in a concentration-dependent fashion by coincubation with a V2/V1-receptor specific antagonist, but not by an OT-receptor specific antagonist. Results implied that stimulation of cAMP- and uPA responses in LLC-PK1 cells by OT was V2-receptor-mediated

Enhanced selectivity of oxytocin antagonists containing sarcosine in position 7

Neurohypophyseal hormone analogues containing sarcosine (Sar) in position 7 were prepared to design more potent and selective oxytocin antagonists. The three analogues (1-3) of [Sar7]arginine-vasopressin ([Sar7]AVP) and six analogues (4-9) of [Sar7]arginine-vasotocin ([Sar7]AVT) had a reduced affinity for antidiuretic V2 receptors. The [Sar7]AVP derivatives (1-3) were potent antiuterotonic (in vitro pA2 = 7.5-8.4, in vivo 6.6-7.1) and antipressor (pA2 = 7.2-8.0) agents. The [Sar7]AVT analogues (4-9) were more potent and selective uterotonic antagonists (in vitro pA2 = 7.9-8.6, in vivo 7.1-7.5); their antipressor potencies were reduced (pA2 = 6.4-7.7). The change of the antagonistic potencies was paralleled by a change in the receptor affinities. Among other antiuterotonic analogues, [Mca1, D-Phe2, Sar7]AVT (4, Mca = beta-mercapto- beta,beta-cyclopentamethyl-enepropionic acid) and [Mca1, D-Tyr(OEt)2,Sar7]AVT (6) were synthesized, two highly potent antiuterotonic compounds (in vitro pA2 = 8.3, in vivo 7.4 and 7.5, respectively) with reduced antipressor activity (pA2 = 6.4) and reduced binding affinity to V2 receptors (Kd = 421 and 35 nM, respectively) and no anti-antidiuretic effect. Another potent antiuterotonic analogue, [Mca1,D-Trp2,-Sar7]AVT (9, in vitro pA2capability to V2 receptors (Kd approximately 0.3 mM). These analogues should lead to the design of even more potent and selective oxytocin antagonists

Lateral mobility of the antagonist-occupied V₂ vasopressin receptor in membranes of renal epithelial cells

The lateral mobility of membrane integral receptors has been implicated as playing a significant role in signal transduction. The adenylate cyclase-coupled vasopressin V2 receptor has been shown to be highly laterally mobile in membranes of LLC-PK1 renal epithelial cells at physiological temperature using a fluorescent vasopressin agonist, with lateral mobility of the V2 receptor proposed to play a role in both adenylate cyclase activation and ligand induced receptor internalization and down-regulation. This study reports the synthesis and characterization of two new fluorescent antagonists [(beta-mercapto-beta,beta-cyclopentamethylene propionic acid)1,D-Tyr2,Ile4,Lys9(N6-fluoresceinylaminothiocarbonyl )]AVP (FL-AVP-anta) and [(beta-mercapto-beta,beta-cyclopentamethylene propionic acid)1,D-Tyr2,Ile4,Lys9(N6-tetramethylrhodamylaminothioca rbonyl)]AVP (TR-AVP-anta) for the V2 receptor. The latter was used to determine the parameters of lateral mobility of the V2 receptor in the non-activated antagonist-occupied form. Using fluorescence photobleaching techniques, results were largely comparable to those for agonist-occupied receptor, indicating high mobility at 37 degrees C. Antagonistic properties of the V2 receptor ligands are apparently not related to decreased receptor lateral mobility. Photobleaching measurements, however, did show that in contrast to V2 agonist, V2 antagonist did not induce receptor immobilization due to aggregation with time at 37 degrees C, indicating that this could be of mechanistic importance in the internalization process