## 4 Discussion  
The main point of the present study was to evaluate the effect of the administration by different routes of the following vasoconstrtorics: epinephrine, most used by dentists and indicated by the American Heart Association (ADA) [20]; phenylephrine, a substance that acts selectively at adrenergic receptors as an alpha-1 agonist [21]; and felypressin, which has limited studies on its effects and is analogous to vasopressin, that acts by binding to the V1A type receptor [3]. In addition, simulated the possible effects of these vasoconstrtorics on the cardiovascular system of patients who use amitriptyline, frequently used in patients with temporomandibular disorders. During a single experiment, the same animal received, firstly, an infiltration and then an intravenous injection of a specific vasoconstrtor. This sequence was chosen to avoid any cumulative cardiovascular effects. The interval of 30 min between doses was established so that the infiltrated or injected substance could be recaptured by nerve or adjacent cells and/or undergo the process of metabolism and destruction, tissue or hepatic, by the enzymes Monoamine-oxidase (MAO) and Catechol-oxymethyltransferase (COMT), thus avoiding the accumulative effect. In our results, treatment with amitriptyline caused a significant decrease in mean, systolic, and diastolic blood pressure (Table 1). Tricyclic antidepressants have as their classic mechanism of action the inhibition of noradrenaline and serotonin reuptake, through their binding with the transport proteins responsible for this process [14; 22; 23; 24; 25]. In addition, this group of drugs also antagonizes several other receptors, such as H1, 5-HT2, alpha-1 adrenergic, and muscarinic in general. This can produce side effects such as blurred vision, dry mouth, constipation, difficulty urinating, as well as hypotension and sedation. The hypotension observed in our animals may have been produced by a set of conditions, including antagonism of alpha-1 adrenergic receptors, produced by amitriptyline and other tricyclic antidepressants, decreased myocardial contractility and peripheral vasodilation [26]. Amitriptyline treated, (Figure 1B) have significantly increased pressor responses to the three vasoconstrtorics (**_p_ < 0.001), compared to untreated animals (control group) (Figure 1A), when epinephrine is infiltrated into the background of the vestibular sulcus. Tricyclic drugs are known to be norepinephrine and serotonin reuptake inhibitors; as the infiltrated epinephrine is also recaptured by the same transporters, which are inhibited by the action of amitriptyline, this substance could remain longer bound to adrenergic receptors, causing a greater increase in blood pressure. [PERSON] et al., [PERSON] et al. and [PERSON] et al., also agree that epinephrine infiltration in patients treated with tricyclic antidepressants can cause an increase in blood pressure, exactly as observed in our study, where treated animals were more sensitive to epinephrine infiltration [12; 13; 24]. It is also important to emphasize that, even though these animals treated with amitriptyline are more sensitive to the hypertensive effects of epinephrine infiltration, even with the infiltration of the equivalent dose of 8 tubes, the blood pressure variation was less than 8 mmHg, which clinically does not represent any significant change. Regarding felypressin infiltration (Figure 1A), the dose-response curves for blood pressure demonstrate a dose-dependent pattern. The results demonstrate that the amitriptyline treated (Figure 1B) were less sensitive to the action of felypressin, especially when the highest doses used in this study were infiltrated (equivalent to 32 tubes). Felypressin is a known agonist of V1a receptors for vasopressin and its hypertensive action is practically due to its peripheral vasoconstrtoric effects since felypressin acts on V1a receptors widely distributed in the smooth muscle of capillaries, arterioles, and venules [2; 3].