Background: Coronary heart disease has been widely studied in cardiovascular research. However, patients with peripheral artery disease (PAD) have worst outcomes compared to those with coronary artery disease. Therefore, pharmacological studies using femoral artery are highly relevant for a better understanding of the pathophysiologic responses of the PAD. Objective: The aim of this study was to evaluate the pharmacologic properties of the contractile and relaxing agents in rat femoral artery. Methods: Concentration response curves to the contractile phenylephrine (PE) and serotonin (5-HT) and the relaxing agents isoproterenol (ISO) and forskolin were obtained in isolated rat femoral artery. For relaxing responses, tissues were precontracted with PE or 5-HT. Results: The order rank potency in femoral artery was 5-HT > PE for contractile responses. In tissues precontracted with 5-HT, relaxing responses to isoproterenol was virtually abolished as compared to PE-contracted tissues. Forskolin, a stimulant of adenylyl cyclase, partially restored the relaxing response to ISO in 5-HT-precontracted tissues. Conclusion: An interaction between β-adrenergic- and serotoninergic- receptors signaling pathway occurs in femoral artery. Moreover, this study provides a new model to study serotoninergic signaling pathway under normal and pathological conditions which can help understanding clinical outcomes in the PAD.9812934Mewissen, M.W., Stenting in the femoropopliteal arterial segment (2005) Tech Vasc Interv Radiol, 8 (4), pp. 146-149Schainfeld, R.M., Management of peripheral arterial disease and intermittent claudication (2001) J Am Board Fam Pract, 14 (6), pp. 443-450Balzer, J.O., Scheinert, D., Diebold, T., Haufe, M., Vogl, T.J., Biamino, G., Postinterventional transcutaneous suture of femoral artery access sites in patients with peripheral arterial occlusive disease: A study of 930 patients (2001) Catheter Cardiovasc Interv, 53 (2), pp. 174-181Lumsden, A.B., Rice, T.W., Chen, C., Zhou, W., Lin, P.H., Bray, P., Peripheral arterial occlusive disease: Magnetic resonance imaging and the role of aggressive medical management (2007) World J Surg, 31 (4), pp. 695-704Mardikar, H.M., Mukherjee, D., Current endovascular treatment of peripheral arterial disease (2007) Prog Cardiovasc Nurs, 22 (1), pp. 31-37Hoyer, D., Hannon, J.P., Martin, G.R., Molecular, pharmacological and functional diversity of 5-HT receptors (2002) Pharmacol Biochem Behav, 71 (4), pp. 533-554Berger, M., Gray, J.A., Roth, B.L., The expanded biology of serotonin (2009) Annu Rev Med, 60, pp. 355-366Kaumann, A.J., Levy, F.O., 5-hydroxytryptamine receptors in the human cardiovascular system (2006) Pharmacol Ther, 111 (3), pp. 674-706Hannon, J., Hoyer, D., Molecular biology of 5-HT receptors (2008) Behav Brain Res, 195 (1), pp. 198-213Martin, G.R., Eglen, R.M., Hamblin, M.W., Hoyer, D., Yocca, F., The structure and signalling properties of 5-HT receptors: An endless diversity? (1998) Trends Pharmacol Sci, 19 (1), pp. 2-4Nagatomo, T., Rashid, M., Abul, M.H., Komiyama, T., Functions of 5-HT2A receptor and its antagonistsin the cardiovascular system (2004) Pharmacol Ther, 104 (1), pp. 59-81Insel, P.A., Adrenergic receptors: Evolving concepts on structure and function (1989) Am J Hypertens, 2 (3 PART 2), pp. 112S-118SLefkowitz, R.J., Rockman, H.A., Koch, W.J., Catecholamines, cardiac betaadrenergic receptors, and heart failure (2000) Circulation, 101 (14), pp. 1634-1637Zanesco, A., De-Moraes, S., Effect of acute footshock stress on the responsiveness of the isolated rat tail artery to phenylephrine and epinephrine (1992) Braz J Med Biol Res, 25 (1), pp. 63-66Docherty, J.R., Subtypes of functional alpha1- and alpha2-adrenoceptors (1998) Eur J Pharmacol, 361 (1), pp. 1-15Rocha, M.L., Kihara, A.H., Davel, A.P., Britto, L.R., Rossoni, L.V., Bendhack, L.M., Blood pressure variability increases connexin expression in the vascular smooth muscle of rats (2008) Cardiovasc Res, 80 (1), pp. 123-130Chiba, S., Tsukada, M., Vascular responses to beta-adrenoceptor subtypeselective agonists with and without endothelium in rat common carotid arteries (2001) J Auton Pharmacol, 21 (1), pp. 7-13Matsushita, M., Tanaka, Y., Koike, K., Studies on the mechanisms underlying beta-adrenoceptor-mediated relaxation of rat abdominal aorta (2006) J Smooth Muscle Res, 42 (6), pp. 217-225Guimaraes, S., Moura, D., Vascular adrenoceptors: An update (2001) Pharmacol Rev, 53 (2), pp. 319-356Mbaki, Y., Ramage, A.G., Investigation of the role of 5-HT2 receptor subtypes in the control of the bladder and the urethra in the anaesthetized female rat (2008) Br J Pharmacol, 155 (3), pp. 343-356Drescher, W., Varoga, D., Liebs, T.R., Lohse, J., Herdegen, T., Hassenpflug, J.L., Femoral artery constriction by norepinephrine is enhanced by methylprednisolone in a rat model (2006) J Bone Joint Surg Am, 8 (SUPPL. 3), pp. 162-166van Rossum, J.M., Cumulative dose-response curves. II. Technique for the making of dose-response curves in isolated organs and the evaluation of drug parameters (1963) Arch Int Pharmacodyn Ther, 143, pp. 299-330Gupta, S., Mehrotra, S., Villalón, C., de Vries, R., Garrelds, I., Saxena, P., Effects of female sex hormones on responses to CGRP, acetylcholine, and 5-HT in rat isolated arteries (2007) Headache, 47 (4), pp. 564-575Halloul, Z., Meyer, F., Lippert, H., Buerger, T., Ergotamine-induced acute vascular insufficiency of the lower limb--a case report (2001) Angiology, 52 (3), pp. 217-221Jurno, M.E., Chevtchouk, L., Nunes, A.A., de Rezende, D.F., Jevoux, C.C., de Souza, J.A., Ankle-brachial index, a screening for peripheral obstructive arterial disease, and migraine - a controlled study (2010) Headache, 50 (4), pp. 626-630Wang, S.J., Coutinho, V., Sihra, T.S., Presynaptic cross -talk of betaadrenoreceptor and 5-hydroxytryptamine receptor signalling in the modulation of glutamate release from cerebrocortical nerve terminals (2002) Br J Pharmacol, 137 (8), pp. 1371-137
