Patterns and Direct/Indirect Signaling Pathways in Cardiovascular System in the Condition of Transient Increase of NO

Aim To study “patterns” and connections of signaling pathways derived from the rat arterial pulse waveform (APW) under the condition of transient NO increase. Methods and Results The 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. Conclusion We 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.


Figure S1
Relationships of HPs to systolic BP after the first and the fourth administration of 32 nmol kg -1 GSNO. The data and colours were taken from Figure 2A.
5 Figure S2A Relationships of HPs to systolic BP after administrations of 32 nmol kg -1 GSNO. The red line represents the decrease of the systolic BP from the control BP to the lowest BP and blue line represents the increase of the systolic BP from the lowest systolic BP to the control systolic BP ( Figure 3A(a) or 3A(aa)).
7 Figure S2B Relationships of HPs to systolic BP after administrations of 32 nmol kg -1 GSNO. The red line represents the decrease of the systolic BP from the control BP to the lowest BP and blue line represents the increase of the systolic BP from the lowest systolic BP to the control systolic BP ( Figure 3A(a) or 3A(aa)).
9 Figure S2C Relationships of HPs to systolic BP after administrations of 32 nmol kg -1 GSNO. The red line represents the decrease of the systolic BP from the control BP to the lowest BP and blue line represents the increase of the systolic BP from the lowest systolic BP to the control systolic BP ( Figure 3A(a) or 3A(aa)).

Figure S2D
Relationships of HPs to systolic BP after administrations of 32 nmol kg -1 GSNO. The red line represents the decrease of the systolic BP from the control BP to the lowest BP and blue line represents the increase of the systolic BP from the lowest systolic BP to the control systolic BP (Figure 3A(a) or 3A(aa)).
13 Figure S2E Relationships of HPs to systolic BP after administrations of 32 nmol kg -1 GSNO. The red line represents the decrease of the systolic BP from the control BP to the lowest BP and blue line represents the increase of the systolic BP from the lowest systolic BP to the control systolic BP (Figure 3A(a) or 3A(aa)).

Figure S2F
Relationships of HPs to systolic BP after administrations of 32 nmol kg -1 GSNO. The red line represents the decrease of the systolic BP from the control BP to the lowest BP and blue line represents the increase of the systolic BP from the lowest systolic BP to the control systolic BP (Figure 3A(a) or 3A(aa)).

Figure S2G
Relationships of HPs to systolic BP after administrations of 32 nmol kg -1 GSNO. The red line represents the decrease of the systolic BP from the control BP to the lowest BP and blue line represents the increase of the systolic BP from the lowest systolic BP to the control systolic BP (Figure 3A(a) or 3A(aa)).

Figure S2H
Relationships of HPs to systolic BP after administrations of 32 nmol kg -1 GSNO. The red line represents the decrease of the systolic BP from the control BP to the lowest BP and blue line represents the increase of the systolic BP from the lowest systolic BP to the control systolic BP (Figure 3A(a) or 3A(aa)).

Figure S2I
Relationships of HPs to systolic BP after administrations of 32 nmol kg -1 GSNO. The red line represents the decrease of the systolic BP from the control BP to the lowest BP and blue line represents the increase of the systolic BP from the lowest systolic BP to the control systolic BP (Figure 3A(a) or 3A(aa)).