| Cardiovascular disease ranks among the leading causes of morbidity and mortality in adult populations in most countries in the world. Hypertension is a major risk factor of cardiovascular diseases and its underlying pathogenetic mechanisms are still not well elucidated. Significant progress in understanding the etiology of cardiovascular disease has come from recent recognition that inflammation plays a key role in its development. Accumulating clinical evidences have implied that inflammation was also related to hypertension to some extent. Sesso and his colleagues reported a positive relationship between increased serum levels of C-reactive protein and the risk for development of incident hypertension in participants of the Women's Health Study. Bautista et al discovered the serum level of IL-6 elevated in hypertensive patients. More interestingly, Samuelsson showed that prenatal exposure to interleukin-6 resulted in hypertension and increased hypothalamic- pituitary- adrenal axis activity in adult rats. It has been commonly accepted that IL-6 is a pro-inflammatory factor. Thus, prenatal exposure to IL-6 might induce maternal systemic inflammation. Moreover, systemic inflammatory response during pregnancy represents one form of stressful event for the fetus. However, is hypertension in offspring induced single-handedly by IL-6 or by maternal systemic inflammation? This hypothesis has not been tested. Therefore, in order to explore the roles of immuno-inflammtory factors in the development of hypertension, we chose LPS from Gram-negative bacteria and zymosan from eumycete to act as nonspecific immunostimulant to induce maternal systemic inflammation and observe the blood pressure response in offspring. Methods1. Twenty-four time-mated Sprague-Dawley (SD) rats'dams were randomly divided into three groups. On their gestational days 8, 10, and 12, dams in each group received i.p injections of 0.79 mg/kg LPS, 0.79mg/kg zymosan or sterile saline respectively. One hour after the administration, the serum level of TNF-αwas detected by ELISA method. The pups were randomly chosen to be included in this study (males: controls, n=12; LPS-treated, n = 12; zymosan-treated, n=12; females: controls, n =12; LPS-treated, n = 12; zymosan-treated, n=12).2. The pups'body weight was measured once every two weeks since weaned in 4th week until 24th week. Their systolic blood pressure and blood sugar were measured once every tow or six weeks from the 6th to 24th week with tail-cuff method and GOD method, respectively. During the 15th week, their food intake was weighed every day. In their 24th week, the serum level of IL-6 and circulating immune complex (CIC) were measured. After that, the serum level of TNF-αwas measured before and after 2h, 4h and 8h injection of LPS (1mg/kg) to the offspring. At the end of 24th week, the rats were put to death by decapitation. Abdomen adipose tissues were weighed. The serum level of leptin was detected by RIA.Results1. The dams'serum level of TNF-αin LPS group and zymosan group was higher than that in control group (P<0.01). It showed that there was immune challenge after LPS or zymosan exposure in dams.2. There were no significant differences in the number of progeny per dam (P>0.05). Meanwhile, no significant differences were discovered about the ratio of male births to female births in each litter (P>0.05). The body weights of newborn pups did not differ much between the LPS, zymosan and control groups (P>0.05).3. All offspring to LPS or zymosan-exposed dams showed increased systolic blood pressure (P<0.05). They reached the standard of hypertension at the end of 24th week.4. All offspring to LPS or zymosan-exposed dams showed heavier body weights in male from the 6th week ages while female from the 14th week ages, elevated food intake, increased circulating leptin and increased abdomen adipose tissue weights than controls(P<0.05).5. There were no significant differences in blood sugar between LPS, zymosan group and control group (P>0.05).6. There were no significant differences in the serum level of IL-6, TNF-αand CIC when the pups weren't exposed to immuno-inflammatory stimulant between LPS, zymosan group and control group (P>0.05).7. After 2h, 4h, 8h of LPS 1mg/kg i.p., the serum level of TNF-αwas significantly higher in the LPS and zymosan group than that in the control group. The serum level of TNF-αwas positively connected to blood pressure and body weight (P<0.05).Conclusion1. Prenatal exposure to LPS or zymosan could lead to increases in blood pressure and body weight in rats.2. There were no significant differences in the serum level of inflammatory factors IL-6, TNF-αand CIC when the pups weren't exposed to immuno-inflammatory stimulant between LPS, zymosan group and control group.3. The reactions to immuno-inflammatory stimulant in offspring of LPS and zymosan group were more intensive than that in offspring of the control group when they suffered from immune challenge. That was positively connected to blood pressure and body weight.
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