Prenatal Exposure To Inflammatory Stimulant Results In Aortic Vascular Remodeling And Vascular Reactivity In Hypertensive Rats And Its Mechanisms

Essential hypertension ranks among the leading disease of the people which complications are the main reasons resulting in death. 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. Our laboraty traced back to the onset of the essential hypertension from the early stage of the lives which was stimulated by the immuno-inflammatory stimulant. Therefore, we set up the model that prenatal exposure to LPS could lead to increase in blood pressure in offsprings. Accumulating etiopathogenesis evidences have implied that vascular remodeling contributes to increasing not only in peripheral resistance but also in the development and complication of the hypertension. Accordingly, this study was designed to observe the alterations of the aortic vascular remodeling, the hyperplasia and hypertrophy in vascular smooth muscle cells (VSMCs), the proliferation of VSMCs, and the potential underlying mechanisms.Methods:1. Eighteen time-mated Sprague-Dawley (SD) rats'dams were randomly divided into two groups. On their gestational days 8, 10, and 12, dams in each group received i.p injections of 0.79 mg/kg LPS, or sterile saline respectively. The pups were randomly chosen to be included in this study (controls, n=9; LPS-treated, n = 9).2. The pups'systolic blood pressure and body weight were measured once four weeks since weaned in the 6th week until the 34th week by tail-cuff method and analytical balance, respectively.3. At the end of the 34th week, the rats were put to death by decapitation. Aortic vascular remodeling was measured by HE-stained of tissue biopsy. Lumen diameter (LD) and media thickness (MT) of aorta were assayed by Image Pro-Plus software. The expression of PCNA on VSMCs was measured by immunohistochemical method.4. The vascular reactivity of aortic ring from offspring in vitro was measured. The blood plasma level of endothelin-1 (ET-1) was measured by RIA, and the serum level of nitric oxide (NO) was measured by nitrate reductase method.Results:1. All offsprings to LPS-exposed dam showed increased systolic blood pressure since the 6th week (P<0.01). At the end of the 34th week, LPS-exposed dam was (124.24±6.28) mmHg. Contrastly, the blood pressure of control was (111.24±4.56) mmHg (P<0.01).2. The MT, LD and the media/lumen ratios (MT/LD) were increased significantly in LPS-exposed dam by comparison of control (P<0.05).3. Compared with the control, the VSMCs proliferation activity was obviously increased 65% in LPS-exposed dam (P<0.01).4. At the end of the 6th, 12th, 24th, 35th week, the blood plasma level of ET-1 of LPS-exposed dam was higher than the control (P<0.05). Until the 35th week, the level of ET-1 was (148.23±13.42) pg/ml, which was nearly doubled to more than 71.87 pg/ml comparing with the control (P<0.01).5. There were no significant differences in the serum level of NO between LPS group and control group at the end of the 6th, 12th, 24th, 35th week (P>0.05).6. There were no significant differences in the vascular reactivity of aortic ring from offspring in vitro between LPS group and control group at the end of the 6th, 12th, 24th, 35th week (P>0.05).Conclusion:1. Prenatal exposure to LPS leads to increases in blood pressure from the 6th week.2. Prenatal exposure to LPS causes the hypertrophy and hyperplasia of VSMCs and the proliferation of VSMCs.3. The blood plasma level of ET-1 of LPS-exposed dam is higher than the control, but the serum level of NO has no significant differences between them. It illustrates that the dysfunction of imbalance occurs between systolic and diastolic factors releasing by the endothelial cells.4. There were no significant differences in the vasoconstrictor responses to NE and the vasodilator responses to SNP of isolated perfused aortic ring in vitro between LPS group and control group. However, because of heterogeneity of vascular, the vascular reactivity of resistance vessel needs to be studied in depth.