Muscular and cardiac adenosine-induced pain is mediated by A1 receptors

Divisione di Cardiochirurgia, Universita di Roma Tor Vergata, Italy.

OBJECTIVES. This study attempted to establish whether bamiphylline, a selective antagonist of A1 adenosine receptors, prevents the algogenic effects of adenosine in humans. BACKGROUND. Experimental findings indicate that the sympathoexcitatory response elicited by adenosine is mediated by A1 receptors. METHODS. An intrailiac infusion of increasing doses (from 125 to 2,000 micrograms/min) of adenosine was given to 20 patients. Adenosine infusion was then repeated after intrailiac infusion of either bamiphylline or saline solution. In 14 other patients with angina, increasing doses of adenosine (from 108 to 1,728 micrograms/min) were infused into the left coronary artery. Adenosine infusion was then repeated after the intravenous infusion of either bamiphylline or placebo. Coronary blood flow velocity was monitored by a Doppler catheter. Data relative to pain severity are expressed as median and all other data as mean value +/- 1 SD. RESULTS. Bamiphylline prolonged the time to pain onset caused by the intrailiac adenosine infusion from 444 +/- 96 to 749 +/- 120 s (p < 0.001) and reduced pain severity from 45 to 24 mm (p < 0.01). After placebo infusion, the time to pain onset and pain severity were similar to that of baseline (428 +/- 112 vs. 430 +/- 104 s, p = 0.87 and 44 vs. 43 mm, p = 0.67, respectively). Bamiphylline prolonged the time to pain onset caused by intracoronary adenosine infusion from 519 +/- 128 to 603 +/- 146 s (p < 0.01) and reduced pain severity from 58 to 28 mm (p < 0.02). After placebo infusion, the time to pain onset and pain severity were similar to that at baseline (542 +/- 87 vs. 551 +/- 79 s, p = 0.14 and 55 vs. 50 mm, p = 0.61). Maximal coronary blood flow velocities before and after bamiphylline administration were similar (47 +/- 22 vs. 49 +/- 24 cm/s, p = 0.36) as well as before and after placebo administrtion (40 +/- 20 vs. 41 +/- 20 cm/s, p = 0.07). CONCLUSIONS. Bamiphylline reduces adenosine-induced muscular and cardiac pain but does not affect adenosine-induced coronary vasodilation. These findings indicate that at the dose used in this study, bamiphylline does not detectably block vascular A2-receptor-mediated adenosine effects in humans, which suggests that the muscular and cardiac algogenic effects of adenosine are mediated mainly by A1 receptors.

This article has been cited by other articles:

				J. Sawynok Topical and Peripherally Acting Analgesics Pharmacol. Rev., March 1, 2003; 55(1): 1 - 20. [Abstract] [Full Text] [PDF]

				H. R. Middlekauff, A. Doering, and J. N. Weiss Adenosine Enhances Neuroexcitability by Inhibiting a Slow Postspike Afterhyperpolarization in Rabbit Vagal Afferent Neurons Circulation, March 6, 2001; 103(9): 1325 - 1329. [Abstract] [Full Text] [PDF]

				A. Gaspardone, F. Crea, F. Tomai, F. Versaci, A. Pellegrino, L. Chiariello, and P. A. Gioffre Effect of acetylsalicylate on cardiac and muscular pain induced by intracoronary and intra-arterial infusion of bradykinin in humans J. Am. Coll. Cardiol., July 1, 1999; 34(1): 216 - 222. [Abstract] [Full Text] [PDF]

				J.A. Armour Myocardial ischaemia and the cardiac nervous system Cardiovasc Res, January 1, 1999; 41(1): 41 - 54. [Abstract] [Full Text] [PDF]

				H. R. Middlekauff, S. A. Rivkees, H. E. Raybould, M. Bitticaca, J. I. Goldhaber, and J. N. Weiss Localization and functional effects of adenosine A1 receptors on cardiac vagal afferents in adult rats Am J Physiol Heart Circ Physiol, February 1, 1998; 274(2): H441 - H447. [Abstract] [Full Text] [PDF]

				F. Crea and A. Gaspardone New Look to an Old Symptom: Angina Pectoris Circulation, November 18, 1997; 96(10): 3766 - 3773. [Abstract] [Full Text]

				F. Tomai, F. Crea, A. Gaspardone, F. Versaci, A. S. Ghini, R. De Paulis, L. Chiariello, and P. A. Gioffre Phentolamine Prevents Adaptation to Ischemia During Coronary Angioplasty : Role of {alpha}-Adrenergic Receptors in Ischemic Preconditioning Circulation, October 7, 1997; 96(7): 2171 - 2177. [Abstract] [Full Text]

				D. K. Glover, M. Ruiz, J. Y. Yang, B. A. Koplan, T. R. Allen, W. H. Smith, D. D. Watson, R. J. Barrett, and G. A. Beller Pharmacological Stress Thallium Scintigraphy With 2-Cyclohexylmethylidenehydrazinoadenosine (WRC-0470): A Novel, Short-Acting Adenosine A2A Receptor Agonist Circulation, October 1, 1996; 94(7): 1726 - 1732. [Abstract] [Full Text]