Cardiac remodeling, which typically results from chronic hypertension or following an acute myocardial infarction, is a major risk factor for the development of heart failure and, ultimately, death. The renin-angiotensin system (RAS) has previously been established to play an important role in the progression of cardiac remodeling, and inhibition of a hyperactive RAS provides protection from cardiac remodeling and subsequent heart failure. Our previous studies have demonstrated that overexpression of angiotensin-converting enzyme 2 (ACE2) prevents cardiac remodeling and hypertrophy during chronic infusion of angiotensin II (ANG II). This, coupled with the knowledge that ACE2 is a key enzyme in the formation of ANG-(1-7), led us to hypothesize that chronic infusion of ANG-(1-7) would prevent cardiac remodeling induced by chronic infusion of ANG II. Infusion of ANG II into adult Sprague-Dawley rats resulted in significantly increased blood pressure, myocyte hypertrophy, and midmyocardial interstitial fibrosis. Coinfusion of ANG-(1-7) resulted in significant attenuations of myocyte hypertrophy and interstitial fibrosis, without significant effects on blood pressure. In a subgroup of animals also administered [d-Ala(7)]-ANG-(1-7) (A779), an antagonist to the reported receptor for ANG-(1-7), there was a tendency to attenuate the antiremodeling effects of ANG-(1-7). Chronic infusion of ANG II, with or without coinfusion of ANG-(1-7), had no effect on ANG II type 1 or type 2 receptor binding in cardiac tissue. Together, these findings indicate an antiremodeling role for ANG-(1-7) in cardiac tissue, which is not mediated through modulation of blood pressure or altered cardiac angiotensin receptor populations and may be at least partially mediated through an ANG-(1-7) receptor.

In vitro fertilization involving frozen embryo transfer (FET) and donor oocytes increases preeclampsia risk. These IVF protocols typically yield pregnancies without a corpus luteum (CL), which secretes vasoactive hormones. We investigated whether IVF pregnancies without a CL disrupt maternal circulatory adaptations and increase preeclampsia risk. Women with 0 (n=26), 1 (n=23), or >1 (n=22) CL were serially evaluated before, during and after pregnancy. Because increasing arterial compliance is a major physiological adaptation in pregnancy, we assessed carotid-femoral pulse wave velocity (cfPWV) and transit time (cfPWTT). In a parallel, prospective

A novel procedure for initiation of voluntary ethanol consumption in the rat was evaluated in terms of ease of initiation, consistency, and resulting brain ethanol levels. The "jello shot" consists of 10% ethanol in gelatin along with a caloric source (Polycose). Initiation of "jello shot" consumption in Sprague-Dawley rats required no food or water restriction and resulted in initial daily (8.4±0.6 g/kg body weight) and eventual hourly (1.1±0.1 g/kg body weight) intake of ethanol comparable to other procedures using either alcohol-preferring or non-genetically selected rats. Rat intake of ethanol via "jello shots" recovered quickly from environmental alterations and surgical implantation of a guide cannula. During 1-hr free access sessions, consumption of the "jello shot" occurred during the initial 10 minutes and resulted in a dose-related increase in ethanol levels in nucleus accumbens measured using microdialysis. These brain ethanol levels were comparable to those achieved using other selfadministration methods. However, when 0.5 g/kg ethanol was gavaged either in "jello shot" or saline, there was about a 20% decrease in brain ethanol concentrations after gavage of the "jello shot" compared to saline. Even so, lack of a need for initial food or water deprivation and the rapidity with which stable self-administration can be achieved both suggest utility of the "jello shot" as a completely voluntary ethanol procedure. Keywordsethanol self-administration; water deprivation; nucleus accumbens; gelatin; Polycose Alcohol ranks second only to tobacco in terms of the magnitude of adverse public health consequences of its abuse. It is important to develop animal models that emulate conditions of human abuse in order to study neural mechanisms implicated in the etiology of alcoholism. Animal models of alcoholism usually induce animals to drink sufficient quantities of ethanol by initial temporary food or water restriction to encourage rats to partake of unfamiliar tastes. For example, Czachowski et al. (1999) initiates ethanol consumption by providing the 10% ethanol solution as the only available fluid for three days before operant training. Additionally, the fluid received as a result of barpressing is the only fluid available during the first 5-7 days of operant training. Even when sucrose or saccharin is added to the ethanol solution to provide additional reinforcement, rats still need to be initially water deprived in order to encourage them to consume the novel sweet taste (reviewed in Samson & Czachowski 2004). Another 1 Mail proofs to:Joanna Peris, Ph.D. Department of Pharmacodynamics, Box 100487, University of Florida, Gainesville FL 32610, Phone: 352-392-9768, Fax: 352-392-9187, Email: peris@cop.ufl.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is pub...

Commonly used in vitro fertilization protocols produce pregnancies without a corpus luteum (CL), a major source of reproductive hormones. In vitro fertilization pregnancies without a CL showed deficient gestational increases of central (aortic) arterial compliance during the first trimester and were at increased risk for developing preeclampsia. Here, we investigated whether there was generalized impairment of cardiovascular adaptation in in vitro fertilization pregnancies without a CL compared with pregnancies conceived spontaneously or through ovarian stimulation, which lead to 1 and >1 CL, respectively (n=19–26 participants per cohort). Prototypical maternal cardiovascular adaptations of gestation were serially evaluated noninvasively, initially during the follicular phase before conception, 6× in pregnancy, and then, on average, 1.6 years post-partum. The expected increases of cardiac output, left atrial dimension, peak left ventricular filling velocity in early diastole (E wave velocity), peripheral/central arterial pulse pressure ratio, and global AC, as well as decrease in augmentation index were significantly attenuated or absent during the first trimester in women who conceived without a CL, when compared with the 1 and >1 CL cohorts, which were comparable. Thereafter, these cardiovascular measures showed recovery in the 0 CL group except for E wave velocity, which remained depressed. These results provided strong support for a critical role of CL factor(s) in the transformation of the maternal cardiovascular system in early gestation. Regimens that lead to the development of a CL or replacement of missing CL factor(s) may be indicated to improve cardiovascular function and reduce preeclampsia risk in in vitro fertilization pregnancies.

Various non‐invasive methods are available to measure cardiac output (CO) during pregnancy. We compared serial measures of CO using various methods to determine which provided the least variability. Ten patients with spontaneous pregnancy had estimation of CO at baseline prior to becoming pregnant and at the end of the first and third trimesters. Echocardiographic data were used to estimate CO using the Teichholz method, Simpson's biplane method, and the Doppler determined velocity time integral (VTI) method. In addition, a Bioz Dx device was used to estimate CO by impedance cardiography. CO estimated with the VTI method had the lowest beat‐to‐beat variability. CO estimated with the VTI method was higher than CO estimated with the 2D‐Teichholz method and Simpson's method. The percent change in CO during pregnancy was similar for all echo methods (VTI, Teichholz, and Simpson's biplane). Baseline CO determined with impedance cardiography was higher than CO determined with the VTI method. However, change in CO during pregnancy was significantly lower when measured with impedance cardiography. There was marked heterogeneity in the degree of rise in CO during the first trimester (−3 to 55%). The wide variation in the gestational rise in CO was unexpected, and at least in part secondary to variable increase in heart rate. We recommend the use of the Doppler determined VTI method for the estimation of CO in pregnancy.