ABC | Volume 114, Nº2, February 2020

Original Article Fleury et al. Epinephrine and felypressin effects Arq Bras Cardiol. 2020; 114(2):295-303 Statistics For all groups, n = 6. The results were expressed as Mean ± Standard Deviation (SD) for data with normal distribution according to Kolmogorov-Smirnov test. In cases where normal distribution did not occur in one group or more, data were presented as Median ± interquartile interval. When more than one response was obtained from the same animal, repeatd -measures one-way analysis of variance was used (Repeaed- measures One-Way ANOVA). To compare complete curves from two or more groups, repeaed- measures Two-Way analysis of variance was used (Repeaed- measures Two-Way ANOVA). When there was a significant difference between the doses in each curve or in independent groups and normal distribution, comparison was performed by Holm-Sidak’s or Tukeyhodtest. For non-parametric results, Mann-Whitney and Kruskal-Wallis tests were used. The level of significance in this study was set at 5% (p < 0.05). All tests were performed using STATISTICA Software (StatSoft South America). Results Basal blood pressure values during the first five minutes are summarized in Table 1 and used as the initial reference. Atenolol significantly reduced blood pressure in hypertensive animals, whose values were still significantly higher than in control animals. Maximal Hypertensive Response Maximal hypertensive response curves for epinephrine and felypressin, smokers vs. non-smokers, are shown in Figure 2. Smoking significantly increased epinephrine maximal Figure 1 – Schematic study protocol: at 45 days of life, the rats were submitted to clip implantation (1K1C hypertension induction); on the next day, the smoker groups were exposed to cigarette smoke; at 60 days of life, blood pressure was measured by indirect means and atenolol treatment was started; approximately at 75 days of life, direct blood pressure experiments were performed. An example of pulsatile recording after epinephrine administration details how parameters were calculated. Epinefrina 320ng ~ 45 days old (120-140g): 1C1K induction ~ 46-74 days old: cigarette smoke exposition ~ 60 days old: indirect arterial blood pressure measurements and beginning of atenolol treatment ~ 75 days old: direct blood pressure experiments Duração Epinefrina 640ng Epinefrina 1.280ng hypertensive responses in normotensive and atenolol-treated rats. Smoke significantly increased felypressin maximal hypertensive response only in the atenolol-treated group. Minimal Hypotensive Response Figure 3 shows epinephrine minimal hypotensive response curves. Smoke significantly reduced the hypotensive response in normotensive rats (p < 0.05). There was a significant reduction in vasodilator response in 1K1C atenolol-treated group after epinephrine administration. Felypressin, as expected, did now result in significant hypotensive response in the three studied groups (Figure 3B). Heart Rate Epinephried caused a significant increase in heart rate in normotensive and 1K1C hypertensive rats when compared with basal values for each group, but smoking did not alter such effect (Figure 4A). 1K1C atenolol-treated rats showed no changes in this parameter, probably due to the antagonistic effect of atenolol on β 1 -receptors. Felypressin showed a significant reduction in heart rate for non-smoker, normotensive rats when compared with basal values (Figure 4B). Smoke significantly increased heart rate only at 1 and 2 mIU doses of felypressin, when compared with non-smoker normotensive control rats. Response Duration Response duration is described in Table 2. Felypressin showed a significantly longer duration of blood pressure responses than epinephrine in all studied groups. 297