Central autonomic control in spontaneously hypertensive rats: a study on phasic phenomena during rapid-eye-movement sleep

The cardiovascular regulation undergoes wide changes in the different states of sleepwake cycle. In particular, the relationship between spontaneous fluctuations in heart period and arterial pressure clearly shows differences between the two sleep states. In non rapid-eye-movement sleep, heart rhythm is under prevalent baroreflex control, whereas in rapid-eye-movement sleep central autonomic commands prevail (Zoccoli et al., 2001). Moreover, during rapid-eye-movement sleep the cardiovascular variables show wide fluctuations around their mean value. In particular, during rapid-eyemovement sleep, the arterial pressure shows phasic hypertensive events which are superimposed upon the tonic level of arterial pressure. These phasic increases in arterial pressure are accompanied by an increase in heart rate (Sei & Morita, 1996; Silvani et al., 2005). Thus, rapid-eye-movement sleep may represent an “autonomic stress test” for the cardiovascular system, able to unmask pathological patterns of cardiovascular regulation (Verrier et al. 2005), but this hypothesis has never been tested experimentally. The aim of this study was to investigate whether rapid-eye-movement sleep may reveal derangements in central autonomic cardiovascular control in an experimental model of essential hypertension. The study was performed in Spontaneously Hypertensive Rats, which represent the most widely used model of essential hypertension, and allow full control of genetic and environmental confounding factors. In particular, we analyzed the cardiovascular, electroencephalogram, and electromyogram changes associated with phasic hypertensive events during rapid-eyemovement sleep in Spontaneously Hypertensive Rats and in their genetic Wistar Kyoto control strain. Moreover, we studied also a group of Spontaneously Hypertensive Rats made phenotypically normotensive by means of a chronic treatment with an angiotensin converting enzyme inhibitor, the Enalapril maleate, from the age of four weeks to the end of the experiment. All rats were implanted with electrodes for electroencephalographic and electromyographic recordings and with an arterial catheter for arterial pressure measurement. After six days for postoperative recovery, the rats were studied for five days, at an age of ten weeks.The study indicated that the peak of mean arterial pressure increase during the phasic hypertensive events in rapid-eye-movement sleep did not differ significantly between Spontaneously Hypertensive Rats and Wistar Kyoto rats, while on the other hand Spontaneously Hypertensive Rats showed a reduced increase in the frequency of theta rhythm and a reduced tachicardia with respect to Wistar Kyoto rats. The same pattern of changes in mean arterial pressure, heart period, and theta frequency was observed between Spontaneously Hypertensive Rats and Spontaneously Hypertensive Rats treated with Enalapril maleate. Spontaneously Hypertensive Rats do not differ from Wistar Kyoto rats only in terms of arterial hypertension, but also due to multiple unknown genetic differences. Spontaneously Hypertensive Rats were developed by selective breeding of Wistar Kyoto rats based only on the level of arterial pressure. However, in this process, multiple genes possibly unrelated to hypertension may have been selected together with the genetic determinants of hypertension (Carley et al., 2000). This study indicated that Spontaneously Hypertensive Rats differ from Wistar Kyoto rats, but not from Spontaneously Hypertensive Rats treated with Enalapril maleate, in terms of arterial pH and theta frequency. This feature may be due to genetic determinants unrelated to hypertension. In sharp contrast, the persistence of differences in the peak of heart period decrease and the peak of theta frequency increase during phasic hypertensive events between Spontaneously Hypertensive Rats and Spontaneously Hypertensive Rats treated with Enalapril maleate demonstrates that the observed reduction in central autonomic control of the cardiovascular system in Spontaneously Hypertensive Rats is not an irreversible consequence of inherited genetic determinants. Rather, the comparison between Spontaneously Hypertensive Rats and Spontaneously Hypertensive Rats treated with Enalapril maleate indicates that the observed differences in central autonomic control are the result of the hypertension per se. This work supports the view that the study of cardiovascular regulation in sleep provides fundamental insight on the pathophysiology of hypertension, and may thus contribute to the understanding of this disease, which is a major health problem in European countries (Wolf-Maier et al., 2003) with its burden of cardiac, vascular, and renal complications.

Towards Rapid Environmental Assessment and Coastal Forecasting in the Northern Adriatic Sea

A new Coastal Rapid Environmental Assessment (CREA) strategy has been developed and successfully applied to the Northern Adriatic Sea. CREA strategy exploits the recent advent of operational oceanography to establish a CREA system based on an operational regional forecasting system and coastal monitoring networks of opportunity. The methodology wishes to initialize a coastal high resolution model, nested within the regional forecasting system, blending the large scale parent model fields with the available coastal observations to generate the requisite field estimates. CREA modeling system consists of a high resolution, O(800m), Adriatic SHELF model (ASHELF) implemented into the Northern Adriatic basin and nested within the Adriatic Forecasting System (AFS) (Oddo et al. 2006). The observational system is composed by the coastal networks established in the framework of ADRICOSM (ADRiatic sea integrated COastal areaS and river basin Managment system) Pilot Project. An assimilation technique exerts a correction of the initial field provided by AFS on the basis of the available observations. The blending of the two data sets has been carried out through a multi-scale optimal interpolation technique developed by Mariano and Brown (1992). Two CREA weekly exercises have been conducted: the first, at the beginning of May (spring experiment); the second in middle August (summer experiment). The weeks have been chosen looking at the availability of all coastal observations in the initialization day and one week later to validate model results, verifying our predictive skills. ASHELF spin up time has been investigated too, through a dedicated experiment, in order to obtain the maximum forecast accuracy within a minimum time. Energetic evaluations show that for the Northern Adriatic Sea and for the forcing applied, a spin-up period of one week allows ASHELF to generate new circulation features enabled by the increased resolution and its total kinetic energy to establish a new dynamical balance. CREA results, evaluated by mean of standard statistics between ASHELF and coastal CTDs, show improvement deriving from the initialization technique and a good model performance in the coastal areas of the Northern Adriatic basin, characterized by a shallow and wide continental shelf subject to substantial freshwater influence from rivers. Results demonstrate the feasibility of our CREA strategy to support coastal zone management and wish an additional establishment of operational coastal monitoring activities to advance it.