Cardiovascular responses to apelin in two-kidney-one-clip hypertensive rats and its receptor expression in ischemic and non-ischemic kidneys

Background: Apelin and its receptor APJ have been shown to have beneficial effects on cardiovascular function. Apelin was shown to elicit hypotensive effects and also a positive inotropic effect on failing hearts. In this study, we investigated the effect of apelin on blood pressure and cardiac contractility in a two-kidney-one-clip (2K1C) hypertension model. We also assessed the changes in the level of apelin and some other hemodynamically effective hormones in serum and apelin receptor gene expression in nonischemic and ischemic kidneys. Methods: 2K1C was produced by placing a Plexiglas clip around the left renal artery. Four weeks later, blood pressure (BP) and cardiac indices of contractility were measured by power lab system. The sample venous blood was drawn from the jugular vein for biochemical variable measurements. The mRNA and protein level of APJ were determined in the kidneys by RT-PCR and Western blot methods respectively. Results: The findings showed that, 2K1C increased BP from 116/75 in sham group to 200/140 mm Hg in test group. Furthermore, intravenous administration of apelin-13 to hypertensive rats significantly decreased systolic (SBP) and diastolic (DBP) blood pressures in dose of 20 mu g/kg with maximal responses within 2 min of injection. This reduction was long lasting and prominent in dose of 40 mu g/kg. Apelin at dose of 20 mu g/kg increased +LVdp/dt max and -LVdp/dt max. However at dose of 40 mu g/kg SBP, DBP, +LVdp/dt max and -LVdp/dt max strongly decreased. All of the observed effects were completely blocked by apelin antagonist F13A. 2K1C did not change serum apelin, aldosterone and arginine-vasopressin levels but significantly increased angiotensin II level. 2K1C hypertension decreased apelin receptor mRNA and protein expression in contra lateral (nonischemic) kidney, but these were not affected in clipped kidney. Conclusion: Apelin induces hypotensive and positive inotropic effects in medium doses. However, in higher doses it elicits hypotensive and negative inotropic effects in 2K1C rats. Down regulation of apelin receptor in nonischemic kidney of hypertensive rats may play a role in pathophysiology of renovascular hypertension. Apelin together with renin-angiotensin antagonism may play a useful role in treatment of this type of hypertension. (C) 2011 Elsevier B.V. All rights reserved.