Action Of Potassium Channels In The Vascular Remodeling Of Renal Hepertension

BackgroundHypertension, as a common diseases of cardiovascular system, can injure main organs of human body such as heart, kidney, brain and so on. Along with increasing ratio of elders and improving of life standard in the last 20 years, the incidence rate of hypertension is increasing rapidly. Vascular remodeling as an outcome of hypertension contains the changes of structure and function. Vascular remodeling is the main pathological basis of hypertension-related diseases. If we inhibit the vascular remodeling, we will be able to control hypertension better.As we know, a lot of factors influence the vascular remodeling, especially some endogenous vasoactive substances. Some studies of pulmonary hypertension show us that potassium channels can lead to apoptosis and proliferation of vascular smooth muscle cells. What potassium channels play in the course of hypertension has already attracted people's attention. And many studies show that potassium channels may play an important role in the course of hypertension and the vascular remodeling.Objective 1. To investigate the changes of vascular function and the vascularstructure of renal hypertensive rats (RHR) and its relative effects for K+ channels blocker.2. To investigate the vascular remodeling of arteries of the RHR and the effects of K+ opener.Method1. Forty SD rats in 6 weeks old, were divided into 4 groups, every group was 10 rats. Group A was control. To form models of RHR, the other 3 groups were operated with two-kidney, one-clip (2K1C) method. Under antiseptic condition, the left renal artery was exposed and a silver clip with an internal diameter of 0.2 mm was placed around the artery. The 3 groups were divided into RHR group (group B) RHR+ Pinacidil group (group C), RHR+ pinacidil + glibenclamide group (group D). Systolic blood pressure (SBP), heart rate was measured by standard tail-cuff technique before and after operation every week.2. Three weeks after the operation, we treated group C with pinacidil by gastric lavage at doses of 10 mg/kg/day, and group D with pinacidil + glibenclamide by gastric lavage. And group A and group B were treated with 0.9% physiological saline at doses of 10 mg/kg/day.3. Five weeks after the operation, we killed all the rats and got femoral arteries and abdominal aortas from the four groups respectively. Isolated artery rings were used to study the changes of vascular function. We respectively treated group A and group B with KCL, norepinephrine (NE), nitroglycerin (NTG), tetraethylammonium (TEA), and 4-aminopyridine (4-AP), and group C and group D only with KCL, norepinephrine (NE), nitroglycerin (NTG) to observe the effects.4. To observe the changes of the vascular structure of the four groups after HE staining.Results1. One week after the operation, compared with the control group, the SBP of renal hypertensive rats increased significantly (p<0.05), and three weeks after the operation, the SBP achieved the highest level (p<0.01). There was not significant difference in heart rate among the four groups. After drug treated by gastric lavage for two weeks, the SBP of group C decreased compared with group B (p<0.05), and group D was higher than group C (p<0.05).2. Five weeks after the operation, compared with group A, contractions of femoral artery and abdominal aorta of group B induced by KCL or NE were increased significantly in RHR group (p<0.05); contraction induced by TEA or 4-AP decreased significantly (p<0.05); the relaxation induced by NTG decreased significantly (p<0.05).3. Five weeks after the operation, the contraction of femoral artery and abdominal aorta induced by KCL and NE: group C decreased significantly compared with group B (p<0.05); group D increased significantly compared with group C (p<0.05). The relaxation induced by NTG:group C increased significantly compared with group B(p<0.05); group D decreased significantly compared with group C(p<0.05).4. The vascular structure of group B compared to group A changed significantly (p<0.05). The vascular structure among group B, group C and group D did not change significantly (p>0.05).