The renin-angiotensin system and the central nervous system.

One of several factors affecting the secretion of renin by the kidneys is the sympathetic nervous system. The sympathetic input is excitatory and is mediated by beta-adrenergic receptors, which are probably located on the membranes of the juxtaglomerular cells. Stimulation of sympathetic areas in the medulla, midbrain and hypothalamus raises blood pressure and increases renin secretion, whereas stimulation of other parts of the hypothalamus decreases blood pressure and renin output. The centrally active alpha-adrenergic agonist clonidine decreases renin secretion, lowers blood pressure, inhibits ACTH and vasopressin secretion, and increases growth hormone secretion in dogs. The effects on ACTH and growth hormone are abolished by administration of phenoxybenzamine into the third ventricle, whereas the effect on blood pressure is abolished by administration of phenoxybenzamine in the fourth ventricle without any effect on the ACTH and growth hormone responses. Fourth ventricular phenoxybenzamine decreases but does not abolish the inhibitory effect of clonidine on renin secretion. Circulating angiotensin II acts on the brain via the area postrema to raise blood pressure and via the subfornical organ to increase water intake. Its effect on vasopressin secretion is debated. The brain contains a renin-like enzyme, converting enzyme, renin substrate, and angiotensin. There is debate about the nature and physiological significance of the angiotensin II-generating enzyme in the brain, and about the nature of the angiotensin I and angiotensin II that have been reported to be present in the central nervous system. However, injection of angiotensin II into the cerebral ventricles produces drinking, increased secretion of vasopressin and ACTH, and increased blood pressure. The same responses are produced by intraventricular renin. Angiotensin II also facilitates sympathetic discharge in the periphery, and the possibility that it exerts a similar action on the adrenergic neurons in the brain merits investigation.     

Further studies on hypothermia and the blood-brain barrier system.

Rats subjected to five episodes of recurrent, progressively deeper hypothermia showed no difference in cerebral deposition of rubidium tracer at 16 °C and/or apnea from animals lowered to this temperature and/or condition only once. Rats allowed to rewarm from 16 °C showed persisting increased cerebral deposition of tracer at 20 °C with gradual diminution at higher temperatures; at 37 °C, deposition of rubidium tracer in brains of rewarmed rats was not different from that of euthermic rats which were not subjected to hypothermia.     

Effect of microgravity on the respiratory system.

Because the pleural pressure gradient and regional distribution of pulmonary function are gravity dependent, substantial changes may be expected during weightlessness. Although very few measurements have been made during spaceflights, a number of observations during brief periods of weightlessness inside aircraft flying with parabolic trajectories confirm these predictions. Single-breath N2 washouts suggest a marked reduction in the inequality of ventilation distribution seen at 1 G. Similarly, inferences made from cardiogenic oscillations during single-breath washouts suggest a greater uniformity of perfusion during weightlessness. This is supported by changes seen on chest radiographs as well as by more direct measurements of regional blood flow distribution using radioactive iodine-labeled macroaggregates. Vital capacity is only slightly reduced, but functional residual capacity decreases by approximately 10% and maximum expiratory flow rates are slightly decreased, especially at low lung volumes. Weightlessness decreases abdominal girth, increases abdominal compliance, and substantially increases the abdominal contribution to tidal volume during resting breathing. Despite these changes, there does not appear to be any alteration in the temporal pattern of breathing. However, the deposition of inhaled medium-sized aerosol particles is substantially reduced, as predicted by model analyses of gravitational sedimentation. Virtually all these observations describe effects at the very onset of weightlessness. Practically nothing is known of slower functional changes and adaptations to prolonged weightlessness. Systematic repeated measurements during manned spaceflights will hopefully begin to provide some information on this subject in the near future.     

Increased training load and the beta-adrenergic-receptor system on human lymphocytes.

The influence of increased training on the sympathoadrenergic system was investigated. Moderately trained male subjects (n = 15) increased their training within 10 wk by 60%; eight of the subjects increased their training volume, and seven increased their training intensity. Before and after the training, an exhaustive treadmill exercise was carried out. Acute treadmill exercise increased beta-adrenergic receptor number on mononuclear lymphocytes, isoproternol-stimulated cAMP production, and plasma catecholamine concentration. The increase of receptor number can at least partially be explained by a changed lymphocyte composition at rest and after exercise. After training, the exercise-induced increase of beta-adrenergic receptor number was significantly blunted, and the exercise-induced increase of the isoproternol-stimulated cAMP production per beta-receptor was enhanced. Subjects who experienced increased symptoms of physical discomfort and/or mood changes showed an enhanced cAMP production after training. These findings point to an altered regulation of the receptor and postreceptor mechanisms as an effect of a 10-wk period of hard training.     

Wnts and the female reproductive system.

Wnts are intercellular growth and differentiation factors that regulate several key developmental steps, such as gastrulation, neurulation, and organogenesis, including the development of the midbrain, central nervous system, kidney, and limbs. Wnts are also needed for a normal development of the reproductive system. Deficiency of Wnt-4, -5a, and -7a, for example, results in sex reversal, infertility, and/or malformation of the internal and external genitals. Here we focus on the importance of Wnts in the female reproductive system.