AIM: To evaluate the role of chymase in blood pressure regulation and its actions on tissue renin-angiotensin system.METHODS: A two-kidney, one-clip(2K1C) hypertension model was developed in Syrian hamsters, which hav...AIM: To evaluate the role of chymase in blood pressure regulation and its actions on tissue renin-angiotensin system.METHODS: A two-kidney, one-clip(2K1C) hypertension model was developed in Syrian hamsters, which have a human-type chymase. Either an angiotensin(Ang) converting enzyme(ACE) inhibitor(ACE-I; temocapril, 30 mg/kg per day), Ang Ⅱ type 1 receptor antagonist(ARB; CS866, 10 mg/kg per day), or vehicle was administered, beginning 2 wk after renal artery clipping and continued for 16 wk. At the end of this protocol, hearts, aortas, and lungs were removed, and total Ang Ⅱ-forming activities and ACE- and chymasedependent Ang Ⅱ-forming activities were determined.RESULTS: After renal artery clipping, systolic blood pressure in the vehicle group was significantly higher compared with that in a sham-operated group throughoutthe experimental period. Both ACE-I and ARB treatments revealed similar antihypertensive effects. Moreover, in the vehicle group, cardiac total and chymase-dependent Ang Ⅱ-forming activities significantly increased at 18 wk after clipping. Further, cardiac total and chymase-dependent Ang Ⅱ-forming activities decreased significantly after ACE-I or ARB treatment for 16 wk. In addition, chymase-dependent Ang Ⅱ-forming activity significantly increased in the aorta, although these changes were inhibited only by ARB. ARB treatment was more effective compared with ACE-I treatment in reversing the changes in tissue Ang Ⅱ formation, particularly in the aorta, despite their similar antihypertensive effects.CONCLUSION: Chymase does not play a major role in maintaining blood pressure and tissue ACE and chymase are regulated in a tissue-dependent manner in 2K1 C hamster.展开更多
文摘AIM: To evaluate the role of chymase in blood pressure regulation and its actions on tissue renin-angiotensin system.METHODS: A two-kidney, one-clip(2K1C) hypertension model was developed in Syrian hamsters, which have a human-type chymase. Either an angiotensin(Ang) converting enzyme(ACE) inhibitor(ACE-I; temocapril, 30 mg/kg per day), Ang Ⅱ type 1 receptor antagonist(ARB; CS866, 10 mg/kg per day), or vehicle was administered, beginning 2 wk after renal artery clipping and continued for 16 wk. At the end of this protocol, hearts, aortas, and lungs were removed, and total Ang Ⅱ-forming activities and ACE- and chymasedependent Ang Ⅱ-forming activities were determined.RESULTS: After renal artery clipping, systolic blood pressure in the vehicle group was significantly higher compared with that in a sham-operated group throughoutthe experimental period. Both ACE-I and ARB treatments revealed similar antihypertensive effects. Moreover, in the vehicle group, cardiac total and chymase-dependent Ang Ⅱ-forming activities significantly increased at 18 wk after clipping. Further, cardiac total and chymase-dependent Ang Ⅱ-forming activities decreased significantly after ACE-I or ARB treatment for 16 wk. In addition, chymase-dependent Ang Ⅱ-forming activity significantly increased in the aorta, although these changes were inhibited only by ARB. ARB treatment was more effective compared with ACE-I treatment in reversing the changes in tissue Ang Ⅱ formation, particularly in the aorta, despite their similar antihypertensive effects.CONCLUSION: Chymase does not play a major role in maintaining blood pressure and tissue ACE and chymase are regulated in a tissue-dependent manner in 2K1 C hamster.
