ABC | Volume 114, Nº2, February 2020

Original Article Passive Cigarette Smoking Impact on Blood Pressure Response to Epinephrine and Felypressin in 1K1C Hypertensive Rats Treated or not with Atenolol Camila A. Fleury, 1 Elizandra P. M. Almeida, 1 Thiago J. Dionisio, 1 Adriana M. Calvo, 1 Gabriela M. Oliveira, 1 Sandra L. Amaral, 2 Carlos F. Santos, 1 Flávio A. C. Faria 1 Faculdade de Odontologia de Bauru - Universidade de São Paulo - Ciências Biológicas - Farmacologia, 1 Bauru, SP - Brazil Programa Conjunto de Pós-Graduação em Ciências Fisiológicas - Departamento de Educação Física - Faculdade de Ciências - Universidade Estadual de São Paulo, 2 Bauru, SP - Brazil Mailing Address: Carlos F. Santos • Faculdade de Odontologia de Bauru - Universidade de São Paulo - Ciências Biológicas - Farmacologia - Alameda Octávio Pinheiro Brisolla, 9-75. Postal Code 17012-901, Bauru, SP - Brazil E-mail: cfsantos@fob.usp.br Manuscript received June 25, 2018, revised manuscript December 18, 2018, accepted April 24, 2019 DOI: https://doi.org/10.36660/abc.20180433 Abstract Background: Cigarette smoking is usually associated with hypertension and may modify vasoconstrictor response. Objective: The present study aimed to analyze and compare the interaction of passive cigarette smoking and hypertension on epinephrine and felypressin blood pressure effects after intravascular injection. Method: 45-day male Wistar rats had the main left renal artery partially constricted and the right kidney removed (1K1C model). Rats were placed in the chamber for exposition to passive cigarette smoking (10 cigarettes) during 10 min (6 days a week). Hypertensive rats received atenolol (90 mg/kg/day) by gavage for two weeks. Hypotensive and hypertensive response, response duration and heart rate were recorded from direct blood pressure values. The significance level was 5%. Results: Passive cigarette smoking increased maximal hypertensive response to epinephrine in normotensive and 1K1C- atenolol treated rats and to felypressin only in 1K1C-atenolol treated rats; it also reduced epinephrine hypotensive response. Epinephrine increased heart rate in normotensive and hypertensive passive smokers or non-smoker rats. Comparing the two vasoconstrictors, epinephrine showed greater hypertensive response in normotensive smokers, 1K1C-atenolol treated smokers and non-smokers. However, in normotensive-nonsmoker rats, felypressin showed a greater and longer hypertensive effect. Conclusions: Our results suggest that passive cigarette smoking may reduce epinephrine vasodilation and increase hypertensive response when compared to felypressin. Therefore, felypressin may be safe for hypertensive patients to avoid tachycardia and atenolol interaction, but for normotensive and non-smoker patients, epinephrine may be safer than felypressin. (Arq Bras Cardiol. 2020; 114(2):295-303) Keywords: Tobacco Use Disorder; Hypertension; Rats; Felypressin; Atenolol; Epinephrine; Tobacco Smoke Pollution; Nicotine/adverse effects. Introduction Vasoconstrictor drugs are essential for dental and medical procedures performed under local anesthesia, since the local anesthetic must stay in contact with sensitive nerves. One single local anesthetic cartridge administered via intravascular route can be fatal. 1 Therefore, vasoconstrictors are also used to avoid its absorption and adverse effects: seizures, arrhythmia and cardiac arrest. There are studies indicating vasoconstrictor absorption and systemic effects. Epinephrine can be detected in plasma after infiltration and can increase heart rate in normal subjects. 2 There are no clinical data comparing epinephrine and felypressin efficacy or safety, but there is evidence that isolated local anesthetics results in shorter and low quality pain control. 3 Vasoconstrictor drugs have systemic effects that can be critical in patients with cardiovascular diseases: coronary vasoconstriction, tachycardia, increases in cardiac contraction force, etc. Such effects are related to the most common causes of death in the modern world: heart attack, stroke and thrombosis; and patients usually have multifactorial diseases. Cigarette smoking and hypertension are included in the National Cholesterol Education Program algorithm to predict cardiovascular disease risk, addressing both as modifiable causes of atherosclerosis in prevention efforts. 4 The WHO estimates that the global prevalence of adults smoking any tobacco product is 36% in adult men and 8% in adult women. 5 The number of cigarettes show a positive correlation with higher blood pressure values but not with heart rate. 6 Nicotine also affects the autonomous nervous system, having a different effect than cigarette smoking products. 7 Catecholamine release and atherosclerotic lipoproteins 295