Dataset Information

Characterization of Rat Cardiovascular System by Anacrotic/Dicrotic Notches in the Condition of Increase/Decrease of NO Bioavailability.

ABSTRACT: We characterized modes of action of NO-donor S-nitrosoglutathione (GSNO) and NO-synthase inhibitor l-NAME derived from dicrotic (DiN) and anacrotic (AnN) notches of rat arterial pulse waveform (APW) in the condition of increased/decreased NO bioavailability. The cross-relationship patterns of DiN and AnN with 34 hemodynamic parameters (HPs) induced by GSNO and l-NAME are presented. After GSNO bolus administration, approximate non-hysteresis relationships were observed in the difference between DiN-AnN (mmHg) blood pressure (BP) and other 19 HPs, suggesting that these HPs, i.e., their signaling pathways, responding to NO concentration, are directly connected. Hysteresis relationships were observed between DiN-AnN (mmHg) and other 14 HPs, suggesting that signaling pathways of these HPs are indirectly connected. The hysteresis relationships were only observed between the time interval DiN-AnN (ms) and other 34 HPs, indicating no direct connection of signaling pathways. The cross-relationship patterns of DiN-AnN (mmHg), but not DiN-AnN (ms), induced by l-NAME were in accordance to the increased NO bioavailability induced by GSNO. In conclusion, we found the non-hysteresis/hysteresis cross-relationship "patterns" of DiN-AnN intervals to other HPs in the presence of GSNO that revealed their direct or indirect signaling pathways connections. This may contribute to our understanding of biological effects of natural substances that modulate NO production and/or NO signaling pathways.

SUBMITTER: Tomasova L

PROVIDER: S-EPMC7555952 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Characterization of Rat Cardiovascular System by Anacrotic/Dicrotic Notches in the Condition of Increase/Decrease of NO Bioavailability.

Tomasova Lenka L Misak Anton A Kurakova Lucia L Grman Marian M Ondrias Karol K

International journal of molecular sciences 20200912 18

We characterized modes of action of NO-donor S-nitrosoglutathione (GSNO) and NO-synthase inhibitor l-NAME derived from dicrotic (DiN) and anacrotic (AnN) notches of rat arterial pulse waveform (APW) in the condition of increased/decreased NO bioavailability. The cross-relationship patterns of DiN and AnN with 34 hemodynamic parameters (HPs) induced by GSNO and l-NAME are presented. After GSNO bolus administration, approximate non-hysteresis relationships were observed in the difference between D ...[more]

PMID: 32932738

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Project description:AimTo study "patterns" and connections of signaling pathways derived from the rat arterial pulse waveform (APW) under the condition of transient NO increase.Methods and resultsThe right jugular vein of anesthetized Wistar rats was cannulated for administration of NO donor S-nitrosoglutathione. The left carotid artery was cannulated to detect APW. From rat APW, 35 hemodynamic parameters (HPs) and several their crossrelationships were evaluated. We introduced a new methodology to study "patterns" and connections of different signaling pathways, which are suggested from hysteresis and nonhysteresis crossrelationships of 35 rat HPs. Here, we show parallel time-dependent patterns of 35 HPs and some of their crossrelationships under the condition of transient increase of NO bioavailability by administration of S-nitrosoglutathione. Approximate nonhysteresis relationships were observed between systolic blood pressure and at least 11 HPs suggesting that these HPs, i.e., their signaling pathways, responding to NO concentration, are directly connected. Hysteresis relationships were observed between systolic blood pressure and at least 14 HPs suggesting that the signaling pathways of these HPs are indirectly connected. Totally, from the crossrelationships of 35 HPs, one can obtain 595 "patterns" and indication of direct or indirect connections between the signaling pathways.ConclusionWe described the procedure leading virtually to 595 relationships, from which "patterns" for transient NO increase and direct or indirect connections of signaling pathways can be suggested. From a clinical perspective, this approach may be used in animal models and in humans to create a data bank of patterns of crossrelationships of HPs for different cardiovascular conditions. By comparison with unknown patterns of studied APW with the data bank patterns, it would be possible to determine cardiovascular conditions of the studied subject from the recorded arterial blood pressure. Additionally, it can help to find molecular mechanism of particular (patho-) physiological conditions or drug action and may have predictive or diagnostic value.

Project description:Experimental autoimmune encephalomyelitis (EAE), a well-established model of multiple sclerosis, is characterised by microglial activation and lymphocyte infiltration. Induction of EAE in Lewis rats produces an acute monophasic disease characterised by a single peak of disability followed by a spontaneous and complete recovery and a subsequent tolerance to further immunizations. In the current study we have performed a detailed analysis of the dynamics of different lymphocyte populations and cytokine profile along the induction, peak, recovery and post-recovery phases in this paradigm. MBP-injected rats were sacrificed attending exclusively to their clinical score, and the different populations of T-lymphocytes as well as the dynamics of different pro- and anti-inflammatory cytokines were analysed in the spinal cord by flow cytometry, immunohistochemistry and ELISA. Our results revealed that, during the induction and peak phases, in parallel to an increase in symptomatology, the number of CD3+ and CD4+ cells increased progressively, showing a Th1 phenotype, but unexpectedly during recovery, although clinical signs progressively decreased, the number and proportion of CD3+ and CD4+ populations remained unaltered. Interestingly, during this recovery phase, we observed a marked decrease of Th1 and an important increase in Th17 and T-reg cells. Moreover, our results indicate a specific cytokine expression profile along the EAE course characterized by no changes of IL10 and IL17 levels, decrease of IL21 on the peak, and high IL22 levels during the induction and peak phases that markedly decrease during recovery. In summary, these results revealed the existence of a specific pattern of lymphocyte infiltration and cytokine secretion along the different phases of the acute EAE model in Lewis rat that differs from those already described in chronic or relapsing-remitting mouse models, where Th17-cells were found mostly during the peak, suggesting a specific role of these lymphocytes and cytokines in the evolution of this acute EAE model.

Dataset Information

Characterization of Rat Cardiovascular System by Anacrotic/Dicrotic Notches in the Condition of Increase/Decrease of NO Bioavailability.

Publications

Characterization of Rat Cardiovascular System by Anacrotic/Dicrotic Notches in the Condition of Increase/Decrease of NO Bioavailability.

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