This study compared spontaneous baroreflex sensitivity (BRS) estimates obtained from an identical set of data by 11 European centers using different methods and procedures. Noninvasive blood pressure (BP) and ECG recordings were obtained in 21 subjects, including 2 subjects with established baroreflex failure. Twenty-one estimates of BRS were obtained by methods including the two main techniques of BRS estimates, i.e., the spectral analysis (11 procedures) and the sequence method (7 procedures) but also one trigonometric regressive spectral analysis method (TRS), one exogenous model with autoregressive input method (X-AR), and one Z method. With subjects in a supine position, BRS estimates obtained with calculations of alpha-coefficient or gain of the transfer function in both the low-frequency band or high-frequency band, TRS, and sequence methods gave strongly related results. Conversely, weighted gain, X-AR, and Z exhibited lower agreement with all the other techniques. In addition, the use of mean BP instead of systolic BP in the sequence method decreased the relationships with the other estimates. Some procedures were unable to provide results when BRS estimates were expected to be very low in data sets (in patients with established baroreflex failure). The failure to provide BRS values was due to setting of algorithmic parameters too strictly. The discrepancies between procedures show that the choice of parameters and data handling should be considered before BRS estimation. These data are available on the web site (http://www.cbi.polimi.it/glossary/eurobavar.html) to allow the comparison of new techniques with this set of results.

The aim of this study was to compare the systemic hemodynamic effects of four commonly used anesthetic regimens in mice that were chronically instrumented for direct and continuous measurements of cardiac output (CO). Mice (CD-1, Swiss, and C57BL6 strains) were instrumented with a transit-time flow probe placed around the ascending aorta for CO measurement. An arterial catheter was inserted into the aorta 4 or 5 days later for blood pressure measurements. After full recovery, hemodynamic parameters including stroke volume, heart rate, CO, mean arterial pressure (MAP), and total peripheral resistance were measured with animals in the conscious state. General anesthesia was then induced in these mice using isoflurane (Iso), urethane, pentobarbital sodium, or ketamine-xylazine (K-X). The doses and routes of administration of these agents were given as required for general surgical procedures in these animals. Compared with the values obtained for animals in the conscious resting state, MAP and CO decreased during all anesthetic interventions, and hemodynamic effects were smallest for Iso (MAP, -24 +/- 3%; CO, -5 +/- 7%; n = 15 mice) and greatest for K-X (MAP, -51 +/- 6%; CO, -37 +/- 9%; n = 8 mice), respectively. The hemodynamic effects of K-X were fully antagonized by administration of the alpha(2)-receptor antagonist atipamezole (n = 8 mice). These results indicate that the anesthetic Iso has fewer systemic hemodynamic effects in mice than the nonvolatile anesthetics.

Background-Cardiac hypertrophy is an independent risk factor for cardiovascular morbidity and mortality in men and in women. Epidemiological studies indicate that estrogen replacement therapy is cardioprotective; the mechanisms involved in this process, however, are poorly understood. We therefore studied the effect of 17␤-estradiol (E 2 ) on the development of pressure-overload hypertrophy. Methods and Results-Ovariectomized mice receiving E 2 or placebo underwent transverse aortic constriction (TAC) or sham operation. TAC led to a significant increase in ventricular mass compared with sham operation. E 2 treatment reduced cardiac hypertrophy by 31% and 26% compared with placebo 4 and 8 weeks after TAC, whereas it had no effect on the degree of pressure overload, as determined by hemodynamic measurements. Furthermore, E 2 blocked the increased phosphorylation of p38-mitogen-activated protein kinase (MAPK) observed in the placebo-treated animals with TAC. No differences were observed in the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) 1/2 between the groups. E 2 had no effect on the expression of angiotensin-converting enzyme (ACE) or the angiotensin II type 1 receptor. Ventricular atrial natriuretic peptide (ANP) expression was detected only in the animals with TAC. Compared with placebo, E 2 treatment led to an increased expression of ANP in animals with pressure overload. Conclusions-Here, we show that E 2 attenuates the hypertrophic response to pressure overload in mice. This observation demonstrates that hormone replacement therapy with E 2 has direct effects on the heart and may be beneficial in the treatment of postmenopausal women to reduce cardiac hypertrophy. Key Words: hormones Ⅲ hypertrophy Ⅲ myocardium Ⅲ sex T he increase of left ventricular mass represents the structural mechanism of adaptation of the heart in response to pressure overload. The resulting left ventricular hypertrophy is an important negative predictor of cardiac morbidity and mortality and displays significant sex-based differences. 1,2 Estrogen is known to have multiple protective effects on the cardiovascular system. 3 The role of estrogen in the development of cardiac hypertrophy, however, is poorly understood. See p 1333We have shown previously that cardiac myocytes and cardiac fibroblasts contain both known estrogen receptor isoforms, called ␣ and ␤. 4 Via these receptors, estrogen can regulate the cardiac expression of endothelial and inducible NO synthase and connexin 43. 5 Estrogen also modulates the activity of the mitogen-activated protein kinase (MAPK) pathways in cardiac myocytes. 6 The MAPK signaling pathways consist of a sequence of successively acting kinases that ultimately result in the dual phosphorylation and activation of effector kinases such as p38-MAPKs, c-Jun N-terminal kinases (JNKs), and extracellular signal-regulated kinases (ERKs), which subsequently phosphorylate a large array of targets, leading to altered gene expression patterns. 7 These signalin...

Knowledge on murine blood pressure and heart rate control mechanisms is limited. With the use of a tethering system, mean arterial pressure (MAP) and pulse interval (PI) were continuously recorded for periods up to 3 wk in Swiss mice. The day-to-day variation of MAP and PI was stable from 5 days after surgery. Within each mouse (n = 9), MAP and PI varied by 21+/-6 mm Hg and 17+/-4 ms around their respective 24-h averages (97+/-3 mm Hg and 89+/-3 ms). Over 24-h periods, MAP and PI were bimodally distributed and clustered around two preferential states. Short-term variability of MAP and PI was compared between the resting (control) and active states using spectral analysis. In resting conditions, variability of MAP was mainly confined to frequencies <1 Hz, whereas variability of PI was predominantly linked to the respiration cycle (3-6 Hz). In the active state, MAP power increased in the 0.08- to 3-Hz range, whereas PI power fell in the 0.08- to 0.4-Hz range. In both conditions, coherence between MAP and PI was high at 0.4 Hz with MAP leading the PI fluctuations by 0.3-0.4 s, suggesting that reflex coupling between MAP and PI occurred at the same frequency range as in rats. Short-term variability of MAP and PI was studied after intravenous injection of autonomic blockers. Compared with the resting control state, MAP fell and PI increased after ganglionic blockade with hexamethonium. Comparable responses of MAP were obtained with the alpha-blocker prazosin, whereas the beta-blocker metoprolol increased PI similarly. Muscarinic blockade with atropine did not significantly alter steady-state levels of MAP and PI. Both hexamethonium and prazosin decreased MAP variability in the 0.08- to 1-Hz range. In contrast, after hexamethonium and metoprolol, PI variability increased in the 0.4- to 3-Hz range. Atropine had no effect on MAP fluctuations but decreased those of PI in the 0.08- to 1-Hz range. These data indicate that, in mice, blood pressure and its variability are predominantly under sympathetic control, whereas both vagal and sympathetic nerves control PI variability. Blockade of endogenous nitric oxide formation by N(G)-nitro-L-arginine methyl ester increased MAP variability specifically in the 0.08- to 0.4-Hz range, suggesting a role of nitric oxide in buffering blood pressure fluctuations.