This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted 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 Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schmidt, B. M. W. Articles by Wehling, M. Search for Related Content PubMed PubMed Citation Articles by Schmidt, B. M. W. Articles by Wehling, M.

Interaction of Rapid Nongenomic Cardiovascular Aldosterone Effects with the Adrenergic System¹

Institute of Clinical Pharmacology, University Hospital of Mannheim, Faculty for Clinical Medicine Mannheim, University of Heidelberg, 68167 Mannheim, Germany

Address all correspondence and requests for reprints to: Martin Wehling, M.D., Institute of Clinical Pharmacology, Faculty of Clinical Medicine, Ruprecht Karls University of Heidelberg, Theodor Kutzer Ufer 1–3, 68167 Mannheim, Germany. E-mail: martin.wehling{at}upha.ma.uni-heidelberg.de

Interactions between the renin-angiotensin-aldosterone system and the adrenergic system are complex and have mainly been attributed to angiotensin II, with knowledge about aldosterone action much less advanced. Only recently has evidence been forthcoming that aldosterone blunts the baroreceptor reflex and lowers heart rate variability in humans. Both effects point to an adrenergic-like action of aldosterone. It has been proposed that this blunting of baroreceptor sensitivity is mediated nongenomically and that nongenomic aldosterone action itself is modulated by the adrenergic system. The aim of the present study was to prove the hypothesis of an interaction between the autonomic nervous system and rapid, nongenomic aldosterone effects.

We conducted a randomized, double blind, 8-fold cross-over trial on 18 healthy male volunteers. After pretreatment with the ß-blocking agent esmolol, the ß-agonist dobutamine, the ₁-agonist phenylephrine, or placebo, placebo (0.9% NaCl) or aldosterone (0.5 mg) was injected. After aldosterone injection the peak plasma levels were supraphysiological, reaching nanomolar concentrations. Primary target variables were differences in changes in mean arterial blood pressure, systemic vascular resistance, and cardiac output depending on the pretreatment. Cardiovascular parameters were measured by impedance cardiography during the maintained infusion of the adrenergic modulators for 45 min.

Comparing pretreatments, diverse acute, and thus nongenomic, effects of aldosterone on mean arterial blood pressure were observed. After esmolol pretreatment, aldosterone caused an increase in mean arterial blood pressure by 4.1%, whereas after dobutamine pretreatment mean arterial blood pressure decreased by 1.6%, and the difference was statistically significant (P < 0.01). These effects were significant (P < 0.005) for the first 12 min, underlining their nongenomic nature. Our data support the hypothesis that aldosterone, via nongenomic mechanisms, has diverse effects on the cardiovascular system that depend on the preexisting adrenergic state. Furthermore, aldosterone blunts the blood pressure-lowering effect of the ß-blocking agent esmolol by a nongenomic mechanism.

This article has been cited by other articles:

				R. Gros, Q. Ding, S. Armstrong, C. O'Neil, J. G. Pickering, and R. D. Feldman Rapid effects of aldosterone on clonal human vascular smooth muscle cells Am J Physiol Cell Physiol, February 1, 2007; 292(2): C788 - C794. [Abstract] [Full Text] [PDF]

				B. M.W. Schmidt, U. Sammer, I. Fleischmann, M. Schlaich, C. Delles, and R. E. Schmieder Rapid Nongenomic Effects of Aldosterone on the Renal Vasculature in Humans Hypertension, April 1, 2006; 47(4): 650 - 655. [Abstract] [Full Text] [PDF]

				M. Wehling Rapid Effects of Aldosterone: Relevant in Cardiac Ischemia? Hypertension, July 1, 2005; 46(1): 27 - 28. [Full Text] [PDF]

				J. W. Funder The Nongenomic Actions of Aldosterone Endocr. Rev., May 1, 2005; 26(3): 313 - 321. [Abstract] [Full Text] [PDF]

				I. Mazak, A. Fiebeler, D. N. Muller, J.-K. Park, E. Shagdarsuren, C. Lindschau, R. Dechend, C. Viedt, B. Pilz, H. Haller, et al. Aldosterone Potentiates Angiotensin II-Induced Signaling in Vascular Smooth Muscle Cells Circulation, June 8, 2004; 109(22): 2792 - 2800. [Abstract] [Full Text] [PDF]

				B. Boldyreff and M. Wehling Aldosterone: Refreshing a Slow Hormone by Swift Action Physiology, June 1, 2004; 19(3): 97 - 100. [Abstract] [Full Text] [PDF]

				J. Fletcher, A. N. Buch, H. C. Routledge, S. Chowdhary, J. H. Coote, and J. N. Townend Acute aldosterone antagonism improves cardiac vagal control in humans J. Am. Coll. Cardiol., April 7, 2004; 43(7): 1270 - 1275. [Abstract] [Full Text] [PDF]

				D. W. Good, T. George, and B. A. Watts III Aldosterone potentiates 1,25-dihydroxyvitamin D3 action in renal thick ascending limb via a nongenomic, ERK-dependent pathway Am J Physiol Cell Physiol, November 1, 2003; 285(5): C1122 - C1130. [Abstract] [Full Text] [PDF]

				B. M.W. Schmidt, S. Oehmer, C. Delles, R. Bratke, M. P. Schneider, A. Klingbeil, E. H. Fleischmann, and R. E. Schmieder Rapid Nongenomic Effects of Aldosterone on Human Forearm Vasculature Hypertension, August 1, 2003; 42(2): 156 - 160. [Abstract] [Full Text] [PDF]

				R. M. LOSEL, E. FALKENSTEIN, M. FEURING, A. SCHULTZ, H.-C. TILLMANN, K. ROSSOL-HASEROTH, and M. WEHLING Nongenomic Steroid Action: Controversies, Questions, and Answers Physiol Rev, July 1, 2003; 83(3): 965 - 1016. [Abstract] [Full Text] [PDF]

				R. Alzamora, E. T. Marusic, M. Gonzalez, and L. Michea Nongenomic Effect of Aldosterone on Na+,K+-Adenosine Triphosphatase in Arterial Vessels Endocrinology, April 1, 2003; 144(4): 1266 - 1272. [Abstract] [Full Text] [PDF]

				B. M. W. Schmidt, N. Martin, A. C. Georgens, H.-C. Tillmann, M. Feuring, M. Christ, and M. Wehling Nongenomic Cardiovascular Effects of Triiodothyronine in Euthyroid Male Volunteers J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1681 - 1686. [Abstract] [Full Text] [PDF]