ABC | Volume 114, Nº2, February 2020

Original Article Fleury et al. Epinephrine and felypressin effects Arq Bras Cardiol. 2020; 114(2):295-303 by our group that such mixture reduced basal heart rate but did not alter blood pressure responses 10 . Smoke and nicotine can act diversely; nicotine seems to reduce blood pressure when administered acutely, while cigaretes smoking products are associated with increased blood pressure value. 7 . Tobacco smoke sidestream reduces acetylcholine endothelium-dependent relaxation when compared to non-smokers. 14 Our data show that epinephrine-induced hypertensive responses were increased in normotensive and atenolol-treated hypertensive smoker rats when compared to the non-smokers groups (Figure 2) and when compared to felypressin (Figure 5). Blood pressure is defined by cardiac output multiplied by vascular peripheral resistance. Felypressin injected by the intravenous route shows only a vasoconstrictor effect, increasing vascular resistance and leading to an increase in blood pressure values. Epinephrine, on the other hand shows vasoconstrictor and vasodilator, cardiac inotropic and chronotropic effects, leading to complex blood pressure responses after an intravenous injection. Vasodilation reduces hypertensive responses when global blood pressure is measured in and normotensive non-smoker rats showed the highest values of hypotensive response for the lowest doses of epinephrine (Figure 3), reducing hypertensive response when compared with felypressin (Figure 5). Felypressin presents less cardiac effects, but significantly reduced heart rate on normotensive non-smoker rats; such results are consistent with previous studies, where this vasoconstrictor response was associated with prilocaine, 15 which was associated with coronary artery constriction and baroreflex. There is a complex cardiovascular response to nicotine because of ganglionar nicotine receptors which influence autonomous sympathetic and parasympathetic nervous systems. This response includes increase in catecholamine release and altered lipids metabolismwhich explains increase in cardiovascular disease development on in smokes. 8 . According to the Third Report of National Cholesterol Education Program (NCEP), smoking cigarettes has a direct impact on atherosclerosis formation and increases cardiovascular disases risk. 4 The association of hypertension and cigarettes smoking represents a delicate case for vasoconstrictor use. Felypressin response duration was significantly higher than epinephrine’s in all groups, which was expected since vasopressin half-life is approximately 17-35min, 16 while epinephrine has a short half-life due to metabolism and synaptic reuptake. Cigarette smoking increases blood vessel stiffness by different pathways, including oxidative stress increase of endothelin-1 production and formation of smooth muscle cell. 17 . Nicotine-free cigarette smoke extract administered by subcutaneous injection induced endothelial dysfunction, increased blood pressure values and reduced acetylcholine- induced vasodilatation. 18 Although the chemical component responsible for epithelial dysfunction is not clear, cigarettes smoke extract reduces vascular relaxation by increasing oxidative stress and reducing NO bioavailability. 19 Smokers also showed altered lipoprotein metabolism, increased levels of oxidized low density lipoprotein (LDL) which may contribute to vasoconstriction. Chronic smoking impairs NO synthesis and enhances production of reactive oxygen species, while nicotine administration leads to hypertension due to increased sympathetic nervous system. 2,21 Our study showed a significantly reduced minimal hypotensive response on the smoker normotensive group (Figure 3). This reduced vasodilation caused by epinephrine may be related to the increase on the smooth muscle layer promoted by smoke. The heart rate effect was similar in both smoker and non- smoker groups. Conclusion Epinephrine and felypressin dosage corresponded to the content of 0.5 to 16 local anesthetic cartridges administered in bolus via intravascular route in hypertensive rats but there were no deaths. Our results support vasoconstrictor safety in associated vascular problems, mostly especially felypressin seems to be promising vasoconstrictor to smoker patients since there is no interaction with the sympathetic nervous system. Author contributions Conception and design of the research: Fleury CA, Almeida EPM, Amaral SL, Santos CF, Faria FAC; Acquisition of data, Analysis and interpretation of the data and Critical revision of the manuscript for intellectual content: Fleury CA, Moretto E, Dionisio TJ, Calvo AM, Oliveira GM, Amaral SL, Santos CF, Faria FAC; Statistical analysis: Fleury CA, Dionisio TJ, Calvo AM, Oliveira GM, Santos CF, Faria FAC; Writing of the manuscript: Fleury CA, Dionisio TJ, Calvo AM, Oliveira GM, Amaral SL, Santos CF, Faria FAC. Potential Conflict of Interest No potential conflict of interest relevant to this article was reported. Sources of Funding There were no external funding sources for this study. Study Association This article is part of the thesis of master submitted by Elizandra P. M. Almeida, from Faculdade de Odontologia de Bauru - Universidade de São Paulo . Ethics approval and consent to participate This study was approved by the Ethics Committee of the Faculdade de Odontologia de Bauru - Universidade de São Paulo under the protocol number 10/2010. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. 301