Study On Changes Of Insulin And Its Receptor In Hypothalamus And Their Relationship With Blood Pressure In Hypertensive Rats

Hypertension is one of the diseases seriously threatening health of human beings. Hypertension and its complications can cause not only patients' tremendous agony in body and mind, but also a heavy burden to their families and the society. But the pathogenesis remains unclear. Insulin resistance and hyperinsulinmia plays an important role in the development of hypertension. It has been hypothesized from the experimental researches that insulin and insulin receptor are widely distributed and can be synthesized in the central nervous system. On the other hand, previous studies have shown that the central insulin concentration of spontaneous hypertensive rats was higher than that of Wistar rats. And microinjections of insulin into the ventromedial nucleus in the hypothalamus and the lateral ventricle can cause vasodepression and bradycardia via the suppression of both sympathetic nervous system activities and the release of digitalis-like substances. Central nervous system has an important role in the development of hypertension. A deeper understanding of the relationship between the central insulin, insulin receptor and blood pressure will be helpful to explain the pathogenesis of hypertension and offer an experimental basis in the treatment of hypertension.In this study, we have investigated the concentration of insulin in hypothalamus, the Bmax and KD of InsR in cellualr membrane from hypothalamus, InsR mRNA and effects of microinjection of insulin into anterior hypothalamic area on blood pressure and blood glucose at different blood pressure by means of RIA (radioimmunoassay), RBA (radioligandbinding assay of receptor), RT-PCR and microinjection. The main results are as follows:⑴ The insulin was widely and unequally distributed in the rat brain. The insulin concentrations in hypothalamus, hippocampus and olfactory bulb were higher than those in cerebral cortex and midbrain, but much lower in medulla oblongata. The insulin concentration in hypothalamus of SHR was higher than that in Wistar (P<0.05), but the plasma insulin concentration was similar without significant difference. The insulin concentration was not associated with blood pressure in any part of brain. ⑵ With high sucrose diets, the animal model of insulin resistance had been set up successfully in the Wistar rats and the concentration of insulin in plasma was higher than that of SHR and IRH. (P<0.05), the blood pressure was also higher than that of Wistar rats.⑶The quantity of insulin receptor in the hypothalamus was a down- regulated in response to the increased concentration of insulin in SHR, which maybe result from the decreased expression of the InsR mRNA, without changes found in its KD.⑷Microinjection of insulin (0.2pmol) into anterior hypothalamic area significantly decreased mean arterial pressure in SHR group, but not in other groups. Blood glucose concentration was not affected by the microinjection of insulin in all groups. The insulin in the hypothalamus may be a negative feedback to the high arterial pressure and has a protective effect on inhibiting the continuous increase of arterial pressure during the development of hypertension. But the mechanism needs further investigation .