On bias in medical research; reflections on present salt-cholesterol controversies.

A common form of biased reporting is to avoid quoting evidence that contradicts the authors' interpretation of scientific data. Against this background the recommendations by the Institute of Medicine of the National Academies of USA (IOM) regarding a population-based policy of salt restriction have been reviewed. It is suggested that the recommendations may not be valid since some important evidence has not been included in the IOM analysis.

On criticism in bio-medical research--a tribute to Uffe Ravnskov.

The great importance of criticism in science--and its ups-and-downs due to human prejudices and emotions--is discussed in a historical perspective. Towards such a background, attempts are made to evaluate present controversies concerning the widely assumed cause-effect relations between diet-adipositas per se and disorders, like diabetes 2 and atherosclerosis. Seen from a physiological angle, it appears that the real culprits are to a great extent of a different nature, though easily overlooked in e.

Prenatal exposure to interleukin-6 results in hypertension and increased hypothalamic-pituitary-adrenal axis activity in adult rats.

During pregnancy, systemic inflammatory responses induce cytokines that may stress the fetus and contribute to cardiovascular and neuroendocrine dysfunction in adulthood. We evaluated the effects of early and late prenatal exposure to IL-6 on mean systolic arterial pressure (MSAP) and hypothalamic-pituitary-adrenal (HPA) axis regulation in male and female rats at 5-24 wk of age. MSAP and ACTH and corticosterone levels were measured basally and in response to a novel environment, immobilization stress, and stimulation with corticotropin-releasing factor (CRF) and ACTH.

[Salt and blood pressure--centenarian bone of contention].

It is first discussed to what extent salt intake/metabolism may have been modulated since Homo sapiens' global spread from tropical Africa started some 200,000 years ago (10-15,000 generations). The effects on blood pressure, volume, heart rate etc. have been studied along with nearly 100-fold changes in salt intake.

Perspectives on the integrative functions of the 'sympatho-adrenomedullary system'.

An historic survey is given of the gradual change of views and concepts concerning how the sympatho-adrenomedullary system is organized and operates: While it for nearly a century was considered to merely exhibit more or less generalized activation-inhibition responses, experimental studies during the last 50 years have revealed how it instead constitutes a highly sophisticated instrument for control, engaged in a variety of differentiated response patterns by which the brain controls events in major organ systems, down to include their cellular-molecular levels of organisation.

Hypertension and the metabolic syndrome: closely related central origin?

In primary hypertension a mild hyperresponsiveness of hypothalamic, sympatho-hormonal centres to psychosocial stimuli forms a major pathogenetic element, although high salt intake in some subjects may contribute via volume expansion. Hypertension is often associated with another "civilisation" disorder, the metabolic syndrome, defined as abdominal obesity, insulin resistance and dyslipidaemia. According to recent research, the metabolic syndrome has in all likelihood a central neuroendocrine origin in the form of enhanced engagement of the hypothalamic-pituitary-adrenal (HPA) axis.

Importance of the blood pressure-heart rate relationship.

In studies of the effects of salt intake on blood pressure (SBP, MBP, DBP), influences on heart rate (HR) are usually neglected even though the longterm load on both left ventricle (LV) and systemic arteries (SA) is better related to the product of HR x SBP (or MBP) than to pressure alone. After all, altered salt intakes often induce considerable volume-related changes in HR, and the heart operates more economically at low HR and high stroke volume (SV). Thus, about 3/4 of LV metabolism is used for the build-up of systolic tension, while the cost for SV expulsion, or for SV increases, is far lower.

Comments on "endpoints in hypertension": peripheral resistance vessels--though mainly on their involvement as "starting-points".

In SHR, and probably often in human primary hypertension as well, the structural-geometric changes in proximal resistance arteries (r(i) decrease combined with w/r(i) increase) seem to occur so early in life, and are already then so pronounced, that they must serve also as major "starting-points" for this disorder of regulation, besides contributing to late deterioration and "end-point" situations by increasingly interfering with myocardial, cerebral, renal etc. blood supplies, and hence functions. Furthermore, particularly in early phases of primary hypertension they may have some easily overlooked influences on evaluations of average vascular smooth muscle activity, and of overall haemodynamics as well, which is briefly discussed.

Physiological aspects of the "defence" and "defeat" reactions.

By means of tele-receptor signals (vision, hearing, olfaction) the mammalian brain is almost continuously informed about environmental events, and whenever these are interpreted as positive or negative challenges the cerebral "super-controller" can, for coping with the anticipated situation, select the most appropriate among a number of pre-formed hypothalamic reaction patterns. These are organized as combined engagements of the somatomotor, visceromotor and hormonal efferent links, whereby a variety of behavioural responses can be elicited, where each is accompanied by appropriate adjustments of inner organ systems, metabolism, etc., to achieve optimal performance.

Hypertensive structural changes in systemic precapillary resistance vessels: how important are they for in vivo haemodynamics?

Objective: To discuss recent findings that seem to question the importance of structural vascular changes for the raised resistance observed in hypertension.

Main Issues: First, in daily life situations, the proximal resistance sections, which are the main site for vasoconstrictor fibre effects, are also the main site for structural elevation of resistance in hypertension. The most distal ones are crucially important for local flow distribution, and their unaltered design suggests that they are usually protected from pressure elevations by a raised resistance upstream.

Kidneys and primary hypertension--initiators, stabilizers or/and victim-aggravators?

As the kidneys so importantly contribute to longterm blood pressure control, and decisively to e.g. Goldblatt hypertension, it is often assumed that they are "prime movers" also in most variants of primary hypertension.

Pathophysiology of hypertension: differences between young and elderly.

Pathogenesis of hypertension: Primary hypertension has a multifactorial background, consisting of three main elements, (1) polygenic predisposition, (2) excitatory environmental effects and (3) structural upward resetting of the heart and vessels. These three elements are inter-related, since excitatory environmental effects are usually needed to precipitate the functional expression of genetic predisposition (particularly in man) and structural upward resetting is sometimes genetically facilitated. As hypertension progresses, the structural upward resetting becomes the dominating element, underlying the elevation in both pressure and resistance.

The pathophysiology of hypertension. Differences between young and elderly patients.

While structural and functional signs of a genetic predisposition to hypertension may sometimes be detected in the juvenile cardiovascular system, the borderline phase characteristic of young hypertensive patients is often dominated by a 'hyperkinetic' circulatory state. The modest pressure elevation is then mainly due to an increase in cardiac output and accentuated responses to neurohormonal stimuli. During the development of established hypertension, cardiac output gradually returns to normal and the high pressure state is largely a result of chronically elevated systemic resistance with cardiovascular 'structural upward resetting'.