Alteration of local ACE activity and vascular responsiveness during development of 2K1C renovascular hypertension.

OBJECTIVES

This study sought to examine the correlation between development of hypertension and local, including; aorta, heart, kidney, lung, as well as circulatory (serum) ACE activity in two kidney one clip (2K1C) renovascular hypertension.

METHODS

Ten- to twelve-week-old rats undertaken left renal artery clipping. Experiments were carried out in 2, 4, 8, and 12 weeks after induction of hypertension (2, 4, 8 and 12W). After sacrificing, animals blood and tissues including heart, aorta lung and kidney were dissected out and homogenized in Trizma buffer. ACE activity was determined by hydrolysis of the synthetic substrate, Hip-His-Leu and the amount of hippuric acid liberated from the substrate were analyzed by HPLC. Vascular responsiveness was measured using perfusion pressure method.

RESULTS

The systolic blood pressure (SBP) was gradually increased in 2K1C animals and was markedly higher compared to that of controls. The ACE activity in all tissues from 2K1C was significantly different in all groups of 2, 4, 8, and 12 weeks after surgery. The serum ACE activity of 2K1C was markedly increased in 2 and 4W and reached to plateau in 8 and 12W group. Vascular responsiveness to angiotensin I (AngI) was increased during development of hypertension in all groups of animals.

CONCLUSION

These results indicated that there is a positive correlation between augmentation of blood pressure and local ACE activity in various tissues as well as serum, highlighting the significant contribution of local compared to circulatory ACE activity in development of renovascular hypertension.