This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stein, C. M. Articles by Wood, A. J. J. Search for Related Content PubMed PubMed Citation Articles by Stein, C. M. Articles by Wood, A. J. J.

(Hypertension. 1995;25:1294-1300.)
© 1995 American Heart Association, Inc.

Articles

Tachyphylaxis of Human Forearm Vascular Responses Does Not Occur Rapidly After Exposure to Isoproterenol

C. Michael Stein; Richard Nelson; Robert Deegan; Huaibing He; Tadashi Inagami; Marshall Frazer; Kamal F. Badr; Margaret Wood; Alastair J. J. Wood

From the Departments of Pharmacology and Medicine, Vanderbilt University School of Medicine, Nashville, Tenn.

Correspondence to Dr Alastair J.J. Wood, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Medical Research Bldg, Room 546, Nashville, TN 37232-6602.

Abstract In vitro and limited in vivo data suggest that rapid desensitization of ß-adrenoceptor responses occurs after exposure to agonist. Tachyphylaxis to a ß-adrenoceptor agonist would represent a potentially important mechanism for the short-term regulation of vascular tone. The effects of a 4-hour infusion of 400 ng/min intra-arterial isoproterenol on forearm blood flow and presynaptic ß-adrenoceptor–mediated norepinephrine release were determined in eight healthy volunteers. Intra-arterial isoproterenol at 400 ng/min resulted in a significant increase in forearm blood flow in all eight subjects at all time points, with no evidence of tachyphylaxis. In fact, forearm blood flow after 4 hours of the isoproterenol infusion (22.8±3.3 mL/100 mL per minute) was significantly greater than after 7 minutes (14.6±2.8 mL/100 mL per minute), 15 minutes (15.4±2.4 mL/100 mL per minute), and 30 minutes (17.4±3.0 mL/100 mL per minute) of the infusion (P<.05). Similarly, presynaptic ß-adrenoceptor responses showed no evidence of tachyphylaxis, so forearm norepinephrine spillover values after 7 minutes (6.6±0.94 ng/min), 15 minutes (7.6±1.5 ng/min), and 4 hours (8.8±1.1 ng/min) of isoproterenol infusion were increased and similar. Minimal systemic effects were observed, and there was no evidence of tolerance, there being no difference in heart rate after 7 minutes (70.7±2.7 beats per minute) and 4 hours (72.2±3.6 beats per minute) of isoproterenol infusion. Similarly, systemic norepinephrine spillover values at 7 minutes (422.6±60.6 ng/min), 15 minutes (436.3±48.7 ng/min), and 240 minutes (491.4±52.9 ng/min) all increased from a baseline value of 294±28.2 ng/min (P<.05) but were not significantly different from each other. Tachyphylaxis does not occur rapidly after exposure of forearm vascular smooth muscle to the ß-adrenoceptor agonist isoproterenol and is unlikely to play a major role in the rapid regulation of vascular response to a ß-adrenoceptor agonist.

Key Words: isoproterenol • norepinephrine • vasodilation • receptors, adrenergic, beta

This article has been cited by other articles:

				X. F. Figueroa, I. Poblete, R. Fernandez, C. Pedemonte, V. Cortes, and J. P. Huidobro-Toro NO production and eNOS phosphorylation induced by epinephrine through the activation of {beta}-adrenoceptors Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H134 - H143. [Abstract] [Full Text] [PDF]

				E. J. Whalen, A. K. Johnson, and S. J. Lewis {beta}-Adrenoceptor Dysfunction After Inhibition of NO Synthesis Hypertension, September 1, 2000; 36(3): 376 - 382. [Abstract] [Full Text] [PDF]

				C. M. Stein, R. Nelson, H. B. He, M. Wood, and A. J. J. Wood Norepinephrine Release in the Human Forearm : Effects of Epinephrine Hypertension, November 1, 1997; 30(5): 1078 - 1084. [Abstract] [Full Text]

				C. M. Stein, R. Deegan, and A. J. J. Wood Lack of Correlation Between Arterial and Venous ß-Adrenergic Receptor Sensitivity Hypertension, June 1, 1997; 29(6): 1273 - 1277. [Abstract] [Full Text]