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Over the past few years, the research team of Professor
Ding-feng SU has reported an impressive quantity of
experimental data about the relationships between blood pressure
variability (BPV) and end-organ damage, a topic of obvious
clinical interest. This research work has been summarized in
a paper that appeared in the August issue of the renowned
journal Trends in Pharmacological
Sciences[1]. The studies by Su
et al provide convincing evidence that BPV is an
independent cardiovascular risk factor that should be
considered as such and, therefore, might become an important
target for therapeutic interventions. Besides these exciting
perspectives in the prevention and treatment of cardiovascular
diseases, the work by Su et al raises a series of
physiological questions.
In most, if not all, studies by Su
et al, BPV is expressed as the standard deviation of beat-to-beat blood pressure
data[2,3]. The standard deviation provides an index of overall BPV
that incorporates all kinds of blood pressure (BP) variations,
from those resulting from the respiratory cycle to the slow
trends occurring over the whole recording period. However,
when studied in the frequency domain, it becomes apparent
that the bulk of BPV is concentrated at low frequencies
(<0.15 Hz in rats)[4]. In other words, the standard deviation
of BP essentially corresponds to the low-frequency
component of the BP spectra. In the low frequency band, BPV is
mainly the result of opposing interactions between
hemodynamic perturbations and the corrective
feedback provided by the arterial baroreceptor reflex. Hemodynamic
studies in conscious rats with neonatal chemical
sympathectomy[5], chronic sinoaortic baroreceptor
denervation[6], and acute neurohumoral
blockade[7] have revealed that one major source
of slow (or low frequency) hemodynamic perturbations is
the myogenic response of vascular smooth muscle cells that
promotes vasoconstriction in regional circulations when BP
increases and vasodilatation when BP decreases (Figure
1)[8].
Taking into consideration this fundamental underlying
physiology of BPV, the soundest pharmacological approach
to reducing BPV is twofold. First, it would be beneficial to
enhance baroreflex function. Chronic treatment with a
non-antihypertensive dose of ketanserin increases baroreflex
sensitivity while reducing BPV in spontaneously
hypertensive rats[3]. This effect was observed for the cardiac
component of the baroreceptor reflex. It is not known whether this
also applies to the sympathetic component. The second
approach would be to attenuate myogenic responses of
regional circulations (Figure 1). This can be achieved with
dihydropyridine L-type calcium channel blockers. Su
et al have demonstrated that nitrendipine can selectively reduce
BPV[2]. However, this strategy is more problematic than the
first because although the reduction of BPV afforded by
calcium channel blockers would be beneficial in terms of
arterial stiffness and left ventricular workload, this would
probably be achieved at the cost of a reduced protection of
capillary vascular beds (eg in the brain and
kidney)[9]. Further investigations including regional hemodynamic
measurements are required to clarify this issue. Finally, it should be
noted that the research team of Professor Su will soon make
available a rat strain with a spontaneous deficiency in
baroreflex function[10], which will undoubtedly facilitate the
study of pharmacological modulation of BPV.
References
References
1 Su DF, Miao CY. Reduction of blood pressure variability: a new
strategy for the treatment of hypertension. Trends Pharmacol
Sci 2005; 26: 388-90.
2 Liu JG, Xu LP, Chu ZX, Miao CY, Su DF. Contribution of blood
pressure variability to the effect of nitrendipine on end-organ
damage in spontaneously hypertensive rats. J Hypertens 2003;
21: 1961-7.
3 Xie HH, Shen FM, Cao YB, Li HL, Su DF. Effects of low-dose
ketanserin on blood pressure variability, baroreflex sensitivity
and end-organ damage in spontaneously hypertensive rats. Clin
Sci (Lond) 2005; 108: 547-52.
4 Chapuis B, Vidal-Petiot E, Oréa V, Barrès C, Julien C. Linear
modelling analysis of baroreflex control of arterial pressure
variability in rats. J Physiol 2004; 559: 639-49.
5 Zhang ZQ, Julien C, Gustin MP, Cerutti C, Barrès C.
Hemodynamic analysis of arterial pressure lability in sympathectomized
rat. Am J Physiol 1994; 267: H48-56.
6 Zhang ZQ, Barrès C, Julien C. Involvement of vasodilator
mechanisms in arterial pressure lability after sino-aortic baroreceptor
denervation in rat. J Physiol 1995; 482: 435-48.
7 Létienne R, Barrès C, Cerutti C, Julien C. Short-term
haemodynamic variability in the conscious areflexic rat. J Physiol
1998; 506: 263-74.
8 Burattini R, Borgdorff P, Westerhof N. The baroreflex is
counteracted by autoregulation, thereby preventing circulatory
instability. Exp Physiol 2004; 89: 397-405.
9 Griffin KA, Hacioglu R, Abu-Amarah I, Loutzenhiser R,
Williamson GA, Bidani AK. Effects of calcium channel blockers
on "dynamic" and "steady-state step" renal autoregulation. Am
J Physiol Renal Physiol 2004; 286: F1136-43.
10 Su DF, Miao CY. Arterial baroreflex function in conscious rats.
Acta Pharmacol Sin 2002; 23: 673-9.
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