بررسی اثرات تزریق سوبسترای رنین در هسته آمیگدال مرکزی بر فشارخون شریانی و ضربان قلب در موش صحرایی مبتلا به پرفشاری خون کلیوی ـ عروقی

Introduction & Objectives: Previous studies have revealed that induction of two kidney-one clip (2K1C) Goldblatt hypertension in rats eliminates hypertensive response after inactivating of the Central Nucleus of the Amygdala (CA). The present study investigated the possibility of alteration in local Renin Angiotensin System (RAS) activity in CA after hypertension induction and evaluation of cardiovascular response to Renin Substrate (RS) microinjection into CA in Wistar rats. Materials & Methods: Clamps were placed on the left renal arteries to induce 2K1C Goldblatt hypertension. A similar surgery procedure without clipping was done in sham group. Rats were studied eight weeks after surgery. The Mean Arterial Blood Pressure (MAP) and heart rate (HR) were measured directly with indwelling arterial cannula under urethane anesthesia. Rats received bilateral cannulation of the CA for RS microinjection. After bilateral microinjection of consecutive doses of RS (0.5µL- 0.1, 1 & 10 µM) saline and pretreatment of losartan (10µM), saralasin(1nM) or captopril(10µM) before RS into CA, MAP and HR measured and compared between groups. Results: Bilateral microinjection of consecutive doses of RS   into CA increased MAP and HR significantly greater in hypertensive group in comparison with normotensive ones (P<0.001). Bilateral microinjection of saralasin and losartan into the CA of Goldblatt hypertensive rats produced significant decrease in MAP and HR from baseline levels. After pretreatment of saralasin, losartan and captopril effects of 1µM RS microinjection into CA of all groups were inhibited. Conclusion: These results are functionally demonstration of cardiovascular effects of RS after microinjection into CA and that effects have increased after 2K1C hypertension induction. This process may contribute in Goldblatt hypertension pathogenesis. Increased Angiotensin II (AngII) receptors or accelerated proteolytic process of RS to Angiotensin I and II may alter RS microinjection into CA outcome.