Angiotensin-converting enzyme inhibitors (ACEi) improve cardiac function and remodeling and prolong survival in patients with heart failure (HF). Blockade of the renin-angiotensin system (RAS) with an angiotensin II type 1 receptor antagonist (AT 1 -ant) may have a similar beneficial effect. In addition to inhibition of the RAS, ACEi may also act by inhibiting kinin destruction, whereas AT 1 -ant may block the RAS at the level of the AT 1 receptor and activate the angiotensin II type 2 (AT 2 ) receptor. Using a model of HF induced by myocardial infarction (MI) in rats, we studied the role of kinins in the cardioprotective effect of ACEi. We also investigated whether an AT 1 -ant has a similar effect and whether these effects are partly due to activation of the AT 2 receptor. Two months after MI, rats were treated for 2 mo with: (

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Using a high-frequency linear transducer (15L8), we studied 1) the feasibility of performing echocardiography in nonanesthetized mice compared with mice given pentobarbital sodium (Pento) or a mixture of ketamine and xylazine and 2) the feasibility of echocardiographic evaluation of left ventricular (LV) hypertrophy, dilatation, and function in mice with two-kidney, one-clip hypertension or myocardial infarction (MI). Heart rate (HR) in awake mice was 658 +/- 9 beats/min; Pento and ketamine plus xylazine reduced HR to 377 +/- 11 and 293 +/- 19 beats/min, respectively, associated with a significant decrease in shortening fraction (SF), ejection fraction (EF), and cardiac output (CO) and an increase in LV end-diastolic (LVEDD) and end-systolic dimensions (LVESD). Mice with 4 wk of two-kidney, one-clip hypertension had increased LV mass (15.62 +/- 0. 62 vs. 22.17 +/- 1.79 mg) without altered LV dimensions, SF, EF, or CO. Mice studied 4 wk post-MI exhibited obvious LV dilatation and systolic dysfunction, as evidenced by increased LVEDD and LVESD and decreased SF, EF, and CO. Our findings clearly show the adverse impact of anesthesia on basal cardiac function and the difficulty in interpreting data obtained from anesthetized mice. We believe this is the first study to demonstrate the feasibility of using echocardiography to assess cardiovascular function in the nonanesthetized mouse.

prevents cardiac remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growth-regulatory lectin.

Abstract-Recent studies have shown that angiotensin-(1-7) (Ang- [1][2][3][4][5][6][7]), which is generated endogenously from both Ang I and II, is a bioactive component of the renin-angiotensin system and may play an important role in the regulation of blood pressure. However, little is known about its role in regulating the reactivity of the afferent arteriole or the mechanism(s) involved. We hypothesized that Ang-(1-7), acting on specific receptors, participates in the control of afferent arteriole tone. We first examined the direct effect of Ang-(1-7) on rabbit afferent arterioles microperfused in vitro, and we tested whether endothelium-derived relaxing factor/NO and cyclooxygenase products are involved in its actions. To assess the vasodilator effect of Ang-(1-7), afferent arterioles were preconstricted with norepinephrine, and increasing concentrations of Ang-(1-7) were added to the lumen. We found that 10 Ϫ10 to 10 Ϫ6 mol/L Ang-(1-7) produced dose-dependent vasodilatation, increasing luminal diameter from 8.9Ϯ1.0 to 16.3Ϯ1.1 m (PϽ0.006). Indomethacin had no effect on Ang-(1-7)-induced dilatation. N G -nitro-L-arginine methyl ester, a NO synthesis inhibitor, abolished the dilatation induced by Ang-(1-7). We attempted to determine which angiotensin receptor subtype is involved in this process. We found that 10, a potent and selective Ang-(1-7) antagonist, abolished the dilatation induced by Ang-(1-7). An angiotensin II type 1 receptor antagonist (L158809) and an angiotensin II type 2 receptor antagonist (PD 123319) at 10 Ϫ6 mol/L had no effect on Ang-(1-7)-induced dilatation. Our results show that Ang-(1-7) causes afferent arteriole dilatation. This effect may be due to production of NO, but not the action of cyclooxygenase products. Ang-(1-7) has a receptor-mediated vasodilator effect on the rabbit afferent arteriole. This effect may be mediated by Ang-(1-7) receptors, because angiotensin type 1 and type 2 receptor antagonists could not block Ang-(1-7)-induced dilatation. Thus, our data suggest that Ang-(1-7)opposes the action of Ang II and plays an important role in the regulation of renal hemodynamics. Key Words: arterioles Ⅲ angiotensin Ⅲ nitric oxide Ⅲ prostaglandins Ⅲ receptors, angiotensin A ngiotensin II (Ang II) is believed to be the principal bioactive end product of both the circulating system and tissue renin-angiotensin system (RAS). Recent reports have suggested that important central and peripheral actions of the RAS may be conveyed by shorter sequences of Ang peptides, including Ang III, Ang-(3-8), and Ang-(1-7). 1,2 Among the putative RAS mediators, the heptapeptide Ang-(1-7) is particularly interesting because of its physiological actions. It has been shown to activate several subtypes of angiotensin receptors in neural, endothelial, and vascular smooth muscle cell preparations and to exert biological actions in the brain and peripheral vessels that are both complementary to and distinct from those of Ang II. 3 A major target organ of the RAS is the kidney, where Ang II plays a pivotal rol...