Published online before print November 24, 2003, doi: 10.1161/01.HYP.0000105111.06482.7E
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(Hypertension. 2004;43:e1.)
© 2004 American Heart Association, Inc.
Hypertension Electronic Pages |
Letters to the Editor
Rapid Nongenomic Aldosterone Effects in the Human Forearm?
Department of Cardiology, University Hospital of Wales College of Medicine, Wales Heart Research Institute, Cardiff, UK
To the Editor:
Deducing the physiological role of aldosterone from studies using systemic infusions of hormone is difficult because of the interdependent nature of many of the often counter-regulatory organ responses that are evoked.
It is because of such general limitations that venous occlusion plethysmography (VOP), combined with intra-arterial drug infusion, has been used extensively to study (regional) human vascular physiology in vivo. Using this technique, Schmidt et al1 report rapid nongenomic effects of aldosterone (500 ng/min) on human forearm resistance vessels by demonstrating an increase in the forearm blood flow (FBF) ratio between the study arm and control arm. Having previously demonstrated that systemic aldosterone infusion causes an acute increase in systemic vascular resistance,2 and in view of the supraphysiological plasma levels achieved in the venous effluent of the infused arm in their present study,1 it is regrettable that they do not present additional data for both arms individually, as previously recommended by Petrie et al.3 VOP is at its most powerful when dose-response relationships to different drugs or mediators within a single study are compared.4 We previously performed such a dose-response study for incremental doses of intra-arterial aldosterone (10, 50, and 100 ng/min) and, in contrast to Schmidt et al, reported a lack of rapid aldosterone effects on forearm resistance vessels.5 Interestingly, small nonsignificant increases in the FBF ratio in our study were almost exclusively the result of a decrease in FBF in the contralateral arm. Did Schmidt et al observe a similar phenomenon? It is noteworthy that a further study using a much smaller aldosterone dose (
0.9 ng/min) showed a significant decrease in FBF following intra-arterial infusion, in keeping with vasoconstriction.6 The contrasting findings in these 3 studies are difficult to reconcile unless one assumes that nongenomic aldosterone effects follow a bi-phasic dose-dependent pattern exhibiting vasoconstriction at low levels (high physiological level6), a neutral effect at moderately raised levels (levels such as seen in severe heart failure and severe primary hyperaldosteronism5), and vasodilatation at high levels (pharmacological levels1). While we agree that acutely achieved plasma levels may be a poor surrogate marker for potentially more important tissue levels, we would like to point out to the reader that the present study contrasts with previous studies.
References
1. Schmidt BM, Oehmer S, Delles C, Bratke R, Schneider MP, Klingbeil A, Fleischmann EH, Schmieder RE. Rapid nongenomic effects of aldosterone on human forearm vasculature. Hypertension. 2003; 42: 156–160.
2. Schmidt BM, Montealegre A, Janson CP, Martin N, Stein-Kemmesies C, Scherhag A, Feuring M, Christ M, Wehling M. Short term cardiovascular effects of aldosterone in healthy male volunteers. J Clin Endocrinol Metab. 1999; 84: 3528–3533.
3. Petrie JR, Perry C, Cleland SJ, Murray LS, Elliott HL, Connell JM. Forearm plethysmography: does the right arm know what the left is doing? Clin Sci (Lond). 2000; 98: 209–210.[Medline] [Order article via Infotrieve]
4. Benjamin N, Calver A, Collier J, Robinson B, Vallance P, Webb D. Measuring forearm blood flow and interpreting the responses to drugs and mediators. Hypertension. 1995; 25: 918–923.
5. Gunaruwan P, Schmitt M, Taylor J, Lee L, Struthers A, Frenneaux M. Lack of rapid aldosterone effects on forearm resistance vasculature in health. J Renin Angiotensin Aldosterone Syst. 2002; 3: 123–125.
6. Romagni P, Rossi F, Guerrini L, Quirini C, Santiemma V. Aldosterone induces contraction of the resistance arteries in man. Atherosclerosis. 2003; 166: 345–349.[CrossRef][Medline] [Order article via Infotrieve]
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