Invited review: Physiological consequences of intermittent hypoxia: systemic blood pressure.

One of the major manifestations of obstructive sleep apnea is profound and repeated hypoxia during sleep. Acute hypoxia leads to stimulation of the peripheral chemoreceptors, which in turn increases sympathetic outflow, acutely increasing blood pressure. The chronic effect of these repeated episodic or intermittent periods of hypoxia in humans is difficult to study because chronic cardiovascular changes may take many years to manifest. Rodents have been a tremendous source of information in short- and long-term studies of hypertension and other cardiovascular diseases. Recurrent short cycles of normoxia-hypoxia, when administered to rats for 35 days, allows examination of the chronic cardiovascular response to intermittent hypoxia patterned after the episodic desaturation seen in humans with sleep apnea. The result of this type of intermittent hypoxia in rats is a 10- to 14-mmHg increase in resting (unstimulated) mean blood pressure that lasts for several weeks after cessation of the daily cyclic hypoxia. Carotid body denervation, sympathetic nerve ablation, renal sympathectomy, adrenal medullectomy, and angiotensin II receptor blockade block the blood pressure increase. It appears that adrenergic and renin-angiotensin system overactivity contributes to the early chronic elevated blood pressure in rat intermittent hypoxia and perhaps to human hypertension associated with obstructive sleep apnea.     

DIFFERENTIAL EFFECTS OF SEDIMENTS ON SURVIVAL AND GROWTH OF FUCUS SERRATUS EMBRYOS (FUCALES,PHAEOPHYCEAE)1

Recruitment of seaweeds through small reproductive stages is limited on sediment inundated rocky shores and largely unsuccessful in soft sediment environments. Burial in sediment has several potentially negative effects for seaweed propagules, and these effects were differentiated in a laboratory experiment. We investigated how light deprivation, sediment type (grain size, organic content, and origin), and sediment chemistry (oxygen presence and toxicity through hydrogen sulfide) affected survivorship and growth of Fucus serratus L. embryos. Presence of hydrogen sulfide had overriding negative impacts on both survivorship and growth of Fucus embryos, independently of sediment type and light availability. In contrast, simple anaerobiosis generally did not impair survival or growth of the embryos. Fine sediments, 3 mm thick, significantly reduced embryo survivorship, presumably through accumulation of metabolic waste products in the immediate vicinity of the embryos as a consequence of constrained diffusion. This effect was equally pronounced in the presence of a 1‐mm layer of organically rich biodeposits. Irradiance levels did not affect survival of embryos but influenced growth. Decreasing thickness and increasing coarseness of sediments together represented a gradient of enhanced light penetration and diffusion. Growth of embryos increased along this gradient. In nature, soft sediment environments with organically enriched muds (e.g. tidal flats and salt marshes) represent habitats least favorable for colonization through small reproductive stages of seaweeds.     

Physiological and Genomic Consequences of Intermittent Hypoxia: Selected Contribution: Altered vascular reactivity in arterioles of chronic intermittent hypoxic rats

Recurrentepisodic hypoxia (EH) is a feature of sleep apnea that may beresponsible for some chronic cardiovascular sequelae such as systemichypertension. Chronic EH (8 h/day for 35 days) causes elevation ofdiurnal resting (unstimulated) mean arterial blood pressure (MAP) inthe rat. We used in vivo video microscopy to examine arteriolarreactivity in the cremaster muscle of male Sprague-Dawley ratssubjected to 35 days of EH. Cremaster muscles of EH (n = 6) and control (n = 6) rats were exposed to varying doses of norepinephrine (NE) (10¹⁰ to 10⁵M), ACh (10⁹ to 10⁵ M), and endothelin-1(10¹² to 10⁸ M). In a separate experiment,EH (n = 5) and control (n = 6) ratswere given one dose of a nitric oxide synthase (NOS) inhibitor N^G-nitro-L-arginine methylester (L-NAME; 10⁵ M). We also examinedendothelial NOS mRNA from the kidneys of EH-stimulated and control(unstimulated) rats. Telemetry-monitored EH rats showed a 16-mmHgincrease in MAP over 35 days, whereas control rats showed no change.The response to NE and endothelin-1 were similar for EH and controlrats. ACh vasodilatation of arterioles in EH rats was significantlyattenuated compared with that of controls. The degree ofvasoconstriction in response to blockade of the nitric oxide system byL-NAME was significantly less (83% of baseline diameterwith L-NAME) for arterioles of EH rats compared with thatfor controls (61% of baseline diameter), implying lower basal restingnitric oxide release in the EH rats. Whole kidney mRNA endothelial NOSlevels were not different between groups. These data support thehypothesis that chronic elevation of blood pressure associated with EHinvolves increased peripheral resistance from decreased basal releaseor production of nitric oxide after 35 days of EH.

     

Field of genes: the politics of science and identity in the Estonian Genome Project

This case study of the Estonian Genome Project (EGP) analyses the Estonian policy decision to construct a national human gene bank. Drawing upon qualitative data from newspaper articles and public policy documents, it focuses on how proponents use discourse to link the EGP to the broader political goal of securing Estonia's position within the Western/European scientific and cultural space. This dominant narrative is then situated within the analytical notion of the "brand state", which raises potentially negative political consequences for this type of market-driven genomic research. Considered against the increasing number of countries engaging in gene bank and/or gene database projects, this analysis of Estonia elucidates issues that cross national boundaries, while also illuminating factors specific to this small, post-Soviet state as it enters the global biocybernetic economy.     

Analysis of genomic sequences by Chaos Game Representation

MOTIVATION: Chaos Game Representation (CGR) is an iterative mapping technique that processes sequences of units, such as nucleotides in a DNA sequence or amino acids in a protein, in order to find the coordinates for their position in a continuous space. This distribution of positions has two properties: it is unique, and the source sequence can be recovered from the coordinates such that distance between positions measures similarity between the corresponding sequences. The possibility of using the latter property to identify succession schemes have been entirely overlooked in previous studies which raises the possibility that CGR may be upgraded from a mere representation technique to a sequence modeling tool. RESULTS: The distribution of positions in the CGR plane were shown to be a generalization of Markov chain probability tables that accommodates non-integer orders. Therefore, Markov models are particular cases of CGR models rather than the reverse, as currently accepted. In addition, the CGR generalization has both practical (computational efficiency) and fundamental (scale independence) advantages. These results are illustrated by using Escherichia coli K-12 as a test data-set, in particular, the genes thrA, thrB and thrC of the threonine operon.     

Daytime cardiac autonomic activity during one week of continuous night shift

Shift workers encounter an increased risk of cardiovascular disease compared to their day working counterparts. To explore this phenomenon, the effects of one week of simulated night shift on cardiac sympathetic (SNS) and parasympathetic (PNS) activity were assessed. Ten (5m; 5f) healthy subjects aged 18-29 years attended an adaptation and baseline night before commencing one week of night shift (2300-0700 h). Sleep was recorded using a standard polysomnogram and circadian phase was tracked using salivary melatonin data. During sleep, heart rate (HR), cardiac PNS activity (RMSSD) and cardiac SNS activity (pre-ejection period) were recorded. Night shift did not influence seep quality, but reduced sleep duration by a mean of 52 +/- 29 min. One week of night shift evoked a small chronic sleep debt of 5 h 14 +/- 56 min and a cumulative circadian phase delay of 5 h +/- 14 min. Night shift had no significant effect on mean HR, but mean cardiac SNS activity during sleep was consistently higher and mean cardiac PNS activity during sleep declined gradually across the week. These results suggest that shiftwork has direct and unfavourable effects on cardiac autonomic activity and that this might be one mechanism via which shiftwork increases the risk of cardiovascular disease. It is postulated that sleep loss could be one mediator of the association between shiftwork and cardiovascular health.     

Intermittent hypoxia: cell to system

This symposium was organized to present research dealing with the effects of intermittent hypoxia on cardiorespiratory systems and cellular mechanisms. The pattern of neural impulse activity has been shown to be critical in the induction of genes in neuronal cells and involves distinct signaling pathways. Mechanisms associated with different patterns of intermittent hypoxia might share similar mechanisms. Chronic intermittent hypoxia selectively augments carotid body sensitivity to hypoxia and causes long-lasting activation of sensory discharge. Intermittent hypoxia also activates hypoxia-inducible factor-1. Reactive oxygen species are critical in altering carotid body function and hypoxia-inducible factor-1 activation caused by intermittent hypoxia. Blockade of serotonin function in the spinal cord prevents long-term facilitation in respiratory motor output elicited by episodic hypoxia and requires de novo protein synthesis. Chronic intermittent hypoxia leads to sustained elevation in arterial blood pressure and is associated with upregulation of catecholaminergic and renin-angiotensin systems and downregulation of nitric oxide synthases.