Facebook
Twitter
LinkedIn
Email
 |
Checking for direct PDF access through Ovid | |
Excerpt
Efforts have been made to use the rates of release of DβH, chromogranin A and NPY as clinical and experimental neurochemical indices of sympathetic nerve firing rates [2–4]. The theoretical backdrop to these efforts has been the difficulty of quantifying rates of release of noradrenaline from sympathetic nerves. Measurement of the overflow (`spillover') of noradrenaline from individual organs to estimate regional sympathetic nervous system activity is both possible, using isotope dilution methodology [7], and useful, but this technique does not measure actual release rates of the transmitter because the extent of neuronal reuptake of noradrenaline is usually not known. It was hoped that DβH, chromogranin A and NPY measurements, being free of this confounding by neuronal reuptake, would have greater validity than noradrenaline measurements.
It turns out that plasma DβH measurements are not valid for this purpose because plasma DβH concentration in humans is bimodally distributed under a genetic influence independent of sympathetic nervous system activity [3]. Measurement of plasma chromogranin concentrations is more helpful [2], although as yet not widely adopted, with increased values being described in patients with essential hypertension. Plasma NPY measurements have found wider application [8] and are featured in the study by Zoccali et al. [9] on patients with end-stage renal disease in this issue of the journal. NPY is a cotransmitter in sympathetic nerves, particularly in those distributed to the cardiovascular system, and is most strikingly evident in the sympathetic innervation of the arterial wall [10]. NPY, in appearing to be disproportionately released at very high rates of sympathetic nerve firing [4] might be particularly suited to detecting sympathetic nervous activation in conditions such as end-stage renal disease, where sympathetic nervous system stimulation has been well documented in sympathetic nerve recordings provided by clinical microneurography [11,12].
Zoccali et al. [9] describe a broad spread of NPY plasma concentrations in patients with renal failure. Although the results from a reference population of healthy people is not provided for comparison, in the patient tertile with highest NPY values, the NPY plasma concentration is clearly elevated, and accompanied by a high plasma noradrenaline concentration, an elevated heart rate and more pronounced left ventricular hypertrophy. End-stage renal disease (ESRD) is associated with an extraordinarily high incidence of cardiovascular mortality [13]. This has previously been tentatively attributed to the high level of sympathetic tone [11,12] which, in other contexts such as cardiac failure [14], has been demonstrated to contribute directly to myocardial damage and to the development of ventricular dysrhythmias. Zoccali et al. [9] make a very plausible, if perhaps not conclusive, case for NPY released from sympathetic nerves having a specific trophic effect, beyond that resulting from high exposure to noradrenaline, in contributing directly to myocyte growth, for which there is independent experimental evidence [15], and to the development of left ventricular hypertrophy. Cardiac hypertrophy is so prevalent in ESRD as to strongly suggest the presence of important trophic influences acting in concert with the elevated blood pressure.
