Mathematical relationships of patterns of 35 rat haemodynamic parameters for conditions of hypertension resulting from decreased nitric oxide bioavailability

Abstract

Information obtained from the arterial pulse waveform (APW) using haemodynamic parameters (HPs) is useful for characterization of the cardiovascular system in particular (patho)physiological conditions. Our goal was to find out whether the relationships between rat HPs could be described by simple mathematical functions and to find mathematical parameters for conditions of high blood pressure (BP) resulting from decreased NO bioavailability. The right jugular vein of anaesthetized Wistar rats was cannulated for I.V. administration of N -nitro-L-arginine methyl ester (L-NAME). The left common carotid artery was cannulated to detect the APW. From 10 points on the rat APW we defined 35 HPs (some were known already) and found 595 crossrelationships between HPs showing unique patterns for particular cardiovascular conditions.Here we show parallel time-dependent changes of 35 HPs and some of their cross-relationships in condition of high BP induced by L-NAME. We found that most of the time-dependent changes of 35 HPs and their relationships were very well fitted by simple mathematical functions, e.g. a linear function, exponential growth, exponential decay or exponential rise to maximum. The results may enable the mathematical functions to be assigned for decreased NO bioavailability, which may have predictive or diagnostic value for conditions of high BP.Using this approach, it may be possible to find unique cross-relationship patterns of HPs and mathematical functions between HPs for different cardiovascular (patho)physiological or drugmodulating conditions. This knowledge can be used in studying the molecular mechanisms of particular (patho)physiological conditions or drug actions and may have predictive or diagnostic value. K E Y W O R D Smathematical relationships, NO bioavailability, pulse waveform parameters INTRODUCTIONThe information obtained from an arterial pulse waveform (APW) analysis, as shape, amplitude and duration of the waveform, can provide insight into many diseases, including hypertension, coronary artery disease, diabetes and diastolic dysfunction (Nelson et al.,The APW gives useful information on details of the cardiovascular system, e.g. mechanical properties of the arterial tree, arterial stiffness, ventricular-vascular interaction and endothelial function. Several APW parameters have been introduced to characterize the cardiovascular system and the connection of pathological conditions with haemodynamic parameters, e.g. the augmentation index, dicrotic notch position, reflection time and cardiac output (Avolio, Butlin, & Walsh, 312 wileyonlinelibrary.com/journal/eph Experimental Physiology. 2020;105:312-334. 2 MATERIALS AND METHODS 2.1 Ethical approval All procedures were approved by the State Veterinary and Food Administration of the Slovak Republic (No: Ro-1545/15-221) according to the guidelines of Directive 2010/63/EU of the European Parliament. The procurement of animals, the husbandry and the experiments conform to the 'European Convention for the Protection

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

“…The present work is also based on the hypothesis that it is possible to characterize the cardiovascular system in many pathophysiological conditions just from the detailed shape of APW. The HPs and their crossrelationships may provide "patterns" for particular cardiovascular conditions, as we obtained for conditions of prolonged decreased NO bioavailability [20].…”

“…The animals were under anesthesia during the whole experiment and were euthanized with an overdose of Zoletil/xylazine via the jugular vein at the end of the surgical procedure. APW continuous measurement, data analysis, and processing were done essentially as described in [20]. Basically, the right jugular vein of the anesthetized rat was cannulated for administration of experimental substances or medication.…”

“…The letters in parentheses (A) to (R) and (AA) to (RR) refer to graphs in the figures, and each one represents HP; for example, (B) in Figure 2(a) represents heart rate. For more details, see [20].…”

“…The time-dependent changes were observed in most of the HPs. administration of NOS inhibitor, N(ω)-nitro-L-arginine methyl ester (L-NAME) (see Figure 3 in [20]). We compared those data with the data obtained under the conditions of increased NO bioavailability by GSNO ( Figure 6).…”

“…Several APW parameters were shown to be useful for characterization of the cardiovascular system [10][11][12][13][14][15][16][17][18][19]. Recently, we introduced measurement of 35 parallel time-dependent rat hemodynamic parameters (HPs) from which crossrelationships can be evaluated [20]. The present work is also based on the hypothesis that it is possible to characterize the cardiovascular system in many pathophysiological conditions just from the detailed shape of APW.…”