Constitutive Nitric Oxide Synthase in Hypothalami of Normal and Hereditary Diabetes Insipidus Rats and Mice: Role of Nitric Oxide in Osmotic Regulation and its Mechanism
|Title:||Constitutive Nitric Oxide Synthase in Hypothalami of Normal and Hereditary Diabetes Insipidus Rats and Mice: Role of Nitric Oxide in Osmotic Regulation and its Mechanism|
|Authors:||Wang, MD, Hui; Morris, MD, John F.|
|Date Published:||May 01, 1996|
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This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
Wang and Morris' research suggests that NO is a long-term regulator of osmosis and that CNOS in the hypothalamus is regulated by shifts in osmotic pressure. They concluded this after examining and comparing the hypothalamic tissue of normal rats with rats that have hereditary diabetes hypothalamic insipidus, and normal mice with mice that have hereditary nephrogenic diabetes insipidus (NDI). They found that NOS is present in all the major central nervous structures involved in osmotic regulation, and that there are more CNOS positive cells in both large and small cells of the hypothalamus in the rats and mice with diabetes insipidus (DI) than their normal counterparts. This provides new evidence that NO is an important factor in the regulation of body water and electrolyte homeostasis and further suggests that NOS in large cell nuclei is regulated by osmotic status.
Short-term dehydration causes an increase in the number and activity of NOS genes in the hypothalamus, as does an increase in sodium in the blood. In normal rats, only half the cells in a part of the hypothalamus called the supraoptic nucleus indicate the presence of NOS activity, whereas in the rats with diabetes nearly all the cells indicated NOS activity. This indicates that NO in the area is called on to regulate the hypothalamo-neurohypophysial system both in a long-term sense and also when the system is under stress. It also indicates that NOS production will be maximal when coping with the life-long osmotic stimulus experienced by the diabetic rats. The same patterns held true for diabetic mice compared to their normal counterparts.
Wang and Morris' study also found that in normal osmotic conditions, female rats show a significantly larger incidence of NOS activity, which is probably related to their higher estrogen levels.
The use of rats and mice with diabetes insipidus enabled Wang and Morris to approach from a different angle the question of how NO regulates osmosis. The hypothalamic DI rats cannot secrete vasopressin. Their vasopressin neurons are, however, overgrown and extremely active. NDI mice produce VP, but can't respond to it. What the diabetic rats and mice have in common is the life-long osmotic stimulation that results from their respective defects. That both show increased CNOS led the researchers to reason that the increase in CNOS is due to osmotic stimulation rather than any local release of VP. Rather, VP secretion is regulated by NO which is itself modulated by body osmotic status.