Effect of tissue kallikrein gene treatment on blood pressure in type 2 diabetic rats and its mechanism

AIM:To study the effect of tissue kallikrein gene (HK) treatment on blood pressure in type 2 diabetic rats and its mechanism. METHODS:Male Wistar rats were injected with low dose streptozotocin and fed with diets enriched in fat and sugar to form type 2 diabetic model. Recombinant adeno-associated viral vectors (rAAV)-mediated HK gene (HK group) or LacZ gene (LacZ group) was introduced to the diabetic rats. The systolic blood pressure was measured every 2 weeks. The acetylcholine (Ach)-dependent vasodilation response, the synthesis of nitric oxide (NO), the expression of endothelin-1 (ET-1) and endothelin-A receptor (ETA-R) in the aorta were detected. RESULTS:(1) Systolic blood pressure was significantly higher in diabetic rats than that in normal control rats. In HK group, systolic blood pressure was significantly reduced within 2 weeks after injection with rAAV·HK, reached near normal levels at 4 weeks and kept until the experiments ended (16 weeks). (2) In LacZ group, Ach-dependent vasodilation response of isolated aorta was markedly decreased than that in HK group (P<0.01). (3) The concentration of NO in the aorta of HK group were significantly higher than those in LacZ group. The expression of ET-1 and ETA-R mRNA were significantly decreased in HK group compared with those in LacZ group (P<0.01). CONCLUSION:rAAV-mediated HK gene delivery efficiently lowed blood pressure and attenuated the endothelial function partly through increasing the concentration of NO and inhibiting the expression of ET-1 and ETA-R of aorta in type 2 diabetic rats.