Published online before print October 10, 2005, doi: 10.1161/01.HYP.0000187014.92384.a4
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(Hypertension. 2005;46:1095.)
© 2005 American Heart Association, Inc.
Editorial Commentaries |
Baroreflexes in Hypertension
A Mystery Revisited
From the Institute of Physiology, Humboldt University, Berlin, Germany
Correspondence to Dr Pontus B. Persson, Institut für Vegetative Physiologie, Charité Universitätsmedizin Berlin, Tucholskystr. 2, D-10117 Berlin. E-mailpontus.persson{at}charite.de
To date, most studies investigating baroreflexes in hypertension have been performed either by recording baroreflex afferents or by denervating them. In the current issue of Hypertension, Lohmeier et al1 present data on the effects of chronic carotid sinus stimulation (CSS) in hypertensive animals. Striking differences were observed during CSS in dogs with angiotensin II (Ang II)-induced hypertension as compared with control conditions. In line with a previous study,2 baroreflex activation by CSS significantly reduced blood pressure during control. In contrast, the hypotensive effect was markedly attenuated in Ang II hypertensive dogs. This observation fits very well with today’s understanding of baroreflexes in several forms of hypertension.
Remarkably, it is still not fully understood how the autonomic nervous system acts in hypertension, although the issue dates back to the very beginnings of research on cardiovascular reflexes. During that era, it was generally held that baroreflexes continuously buffer sympathetic nervous output. Thus, dissection of the afferent nerves supplying regions of the baroreceptors (carotid sinuses and aortic arch) was thought to increase long-term blood pressure. Koch described what he termed Entzügelungshochdruck (disinhibitory hypertension) in many species.3 Today, neurogenic hypertension is commonly used to describe hypertension following denervation of baroreceptors. The concept of neurogenic hypertension was never seriously questioned until the 1970s when Cowley et al performed long-term studies in conscious dogs. In these experiments, only slight increases in blood pressure were found after baroreceptor denervation. Neurogenic hypertension mainly seems to be observed under special experimental conditions: either in animals that are not fully at rest or in unrestrained, freely moving animals in which blood pressure is recorded over a long period of time.4 Although this seems to be the most representative protocol to simulate human life, movement and postural changes in baroreceptor-denervated animals lead to episodes of severe hypotension, resulting in lower mean arterial pressure (MAP) than in resting animals.
Matton was perhaps the first to find blunted baroreflexes in hypertensive animals,5 and only shortly thereafter McCubbin et al directly demonstrated resetting of the baroreflex operating range in hypertension by electroneurographic techniques.6 Thus, the past understanding was that baroreflexes are of minor importance during chronic hypertension because they will completely reset to any new MAP level. Lohmeier et al1 show that under control conditions, CSS indeed lowers MAP over several days. Thus, there is no, or very little, resetting taking place. The situation during Ang II-induced hypertension is very different. Here, Lohmeier et al1 observe significant long-term attenuation of CSS effects on MAP. This is in-line with a series of very recent studies, one which has shown that baroreceptors may indeed be able to influence long-term MAP.7 Furthermore, it has been shown that the baroreflex may not completely reset, at least not with regard to renal sympathetic nerve activity.8 Interestingly, Ang II-mediated sympathoinhibition to the kidney relies critically on intact baroreflexes.9
With regard to the present study of Lohmeier et al,1 it is particularly interesting that renal sympathetic nerve activity has been assumed to be resistant to resetting in response to Ang II-induced hypertension.10 In the study by Lohmeier et al,1 effects of CSS on MAP taper off: one possibility is that there is gradual recovery of sympathetic drive to the kidney. This would not be in-line with nonresetting baroreflex response to renal sympathetic nerve activity. It rather seems that there exists a neural setpoint for long-term MAP, which is only acutely modulated by the baroreflex.11
In light of these studies, our view of the baroreflex requires rethinking. The baroreflex is probably neither fully in control of MAP nor is it ever totally irrelevant for long-term MAP. Baroreflexes are one of many control elements acting in concert to provide the most appropriate response to a given challenge. Completely eliminating the reflex, as done by denervation, or maximum stimulation of the reflex provides valuable insight into cardiovascular control under extreme conditions. However, these may not fully elucidate a subtly controlled interaction between the neurohumoral mechanisms and the kidney, as seen in circulatory homeostasis. More studies of the type presented by Lohmeier et al1 are required.
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Footnotes |
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The opinions expressed in this editorial commentary are not necessarily those of the editors or of the American Heart Association.
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References |
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 Top References |
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1. Lohmeier TE, Dwyer TM, Hildebrandt DA, Irwin ED, Rossing MA, Serdar DJ, Kieval RS. Influence of Prolonged Baroreflex Activation on Arterial Pressure in Angiotensin Hypertension. Hypertension. 2005; 46: 1194–1200.
2. Lohmeier TE, Irwin ED, Rossing MA, Serdar DJ, Kieval RS. Prolonged activation of the baroreflex produces sustained hypotension. Hypertension. 2004; 43: 306–311.
3. Koch E. Die reflektorische Selbststeurung des Kreislaufs. Steinkopff, Dresden; 1931.
4. Cowley AW Jr, Liard JF, Guyton AC. Role of baroreceptor reflex in daily control of arterial blood pressure and other variables in dogs. Circ Res. 1973; 32: 564–576.
5. Matton G. Carotid sinus and neurogenic and renal hypertension. J Physiol. 1954; 126: 13P–14P.
6. McCubbin JW, Green JH, Page IH. Baroceptor function in chronic renal hypertension. Circ Res. 1956; 4: 205–210.
7. Thrasher TN. Effects of chronic baroreceptor unloading on blood pressure in the dog. Am J Physiol Regul Integr Comp Physiol. 2005; 288: R863–R871.
8. Malpas SC. What sets the long-term level of sympathetic nerve activity:is there a role for arterial baroreceptors? Am J Physiol Regul Integr Comp Physiol. 2004; 286: R1–R12.
9. Barrett CJ, Guild SJ, Ramchandra R, Malpas SC. Baroreceptor denervation prevents sympathoinhibition during angiotensin II-induced hypertension. Hypertension. 2005; 46: 168–172.
10. Barrett CJ, Malpas SC. Problems, possibilities, and pitfalls in studying the arterial baroreflexes’ influence over long-term control of blood pressure. Am J Physiol Regul Integr Comp Physiol. 2005; 288: R837–R845.
11. Osborn JW, Jacob F, Guzman P. A neural set point for the long-term control of arterial pressure: beyond the arterial baroreceptor reflex. Am J Physiol Regul Integr Comp Physiol. 2005; 288: R846–R855.
Related Article:
Hypertension 2005 46: 1194-1200.
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