Search

The purpose of this study was to evaluate the relationship between the circadian profile of the vasorelaxing substances calcitonin gene-related peptide (CGRP) and epoxyeicosatrienoic acids (EETs) and the vasconstrictive agent endothelin-1 (ET1) and the daily rhythms of cardiac hemodynamic indices (CHI) and baroreflex (BRS) in Wistar rats with 1 kidney-1 clip model of arterial hypertension (1K-1C AH). The animals were divided into 3 groups: I- sham-operated (SO), II- 4-week and III- 8-week 1K-1C AH rats. Plasma concentration of ET1, CGRP and EET's were investigated every 4 h. In conscious freely moving 1K-1C AH rats unlike SO animals blood pressure (BP), heart period (HP) and BRS underwent significant circadian fluctuations, with more marked increase in mean values of BP in 8-week hypertensive rats in comparison to 4-week hypertensive rats (179 ± 5 vs. 162 ± 4 mm Hg, p < 0.05). These alterations correlated with more significant reduction in HP (138 ± 5 vs. 150 ± 6 ms, p < 0,05) and BRS (0.44 ± 0.04 vs. 0.58 ± 0.04 ms mm Hg -1 , p < 0.05) in 8-week 1K-1C AH rats. The acrophases of BP in 8-week 1K-1C AH rats in comparison with 4-week were shifted to more late night hours (1:58 a.m. vs. 11:32 p.m.) and in both groups of animals corresponded to lowest circadian plasma levels of CGRP and EETs and to greatest level of ET1. SO rats were characterized by lower values of BP (121 ± 3 mm Hg, p < 0,05) and higher indices of HP (158 ± 2 ms, p < 0,05) and BRS (0.86 ± 0.02 ms mmHg -1 , p < 0,001) in comparison with 1K-1C AH rats 4-week duration. The acrophases of BP, HP and BRS in hypertensive animals were revealed at 14.8 ± 0.5 h, 13.6 ± 0.4 h and 13.1 ± 0.2 h, which correlated with maximal circadian contents of ET1 and CGRP at 24:00 h and EETs at 12:00 h and were shifted in comparison to sham-operated group. In rats with 1K-1C AH, plasma levels of ET1, CGRP and EETs undergo circadian fluctuation with corresponding alterations in CHI and BRS which are more markedly expressed on the late stage of diseases and could be used in future for predictive, preventive, and personalized treatment of arterial hypertension., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2019 The Author(s).)

The purpose of this study was to evaluate the influence of zafirlukast (Z), quercetin (Q) and their combination on baroreflex sensitivity (BRS), endothelin-1 (E1) plasma concentration and the severity of ventricular arrhythmias (VA) occurring during myocardial infarction (MI). In anaesthetized Wistar rats, MI was induced by ligation of the left anterior descending coronary artery (CAL). Animals were divided into the five groups: I--sham-operated (SO); II--CAL; III--CAL+Z (0.25 mg/kg intraperitoneally 1 hour prior and 12-24 hour after CAL); IV--CAL+Q (1.5 mg/kg by i.v. injection after anesthesia and every 24 hour during 72 hour); V--CAL+Z+Q as above. CAL after 1 hour was accompanied by high incidence of VA associated with a significant mortality (68% at 72 hour) as compared with SO rats. In survived rats BRS was greatly attenuated (0.44 +/- 0.08 ms/mmHg) vs. SO animals (0.92 +/- 0.14 ms/mmHg, p < 0.05) that correlated to increase E1 plasma concentration (9.2 +/- 0.6 pg/ml) vs. SO rats (2.9 +/- 0.4 pg/ml, p < 0.001). Q did not influence markedly on the severity of VA or rats mortality, while Z and Z+Q decreased mortality in rats in compare to II group of animals (from 68%-42% and 30%), increased the reduced BRS resulting from MI (+38.5% and +55.4%, p < 0.05) and blunted the increase of E1 (-34.8% and -43.5% respectively, p < 0.05). Our results suggested a possible beneficial combine action of Z and Q on MI.