Effects of long-term angiotensin converting enzyme inhibition on cardiovascular variability in aging rats Valdo Jose ´ Dias da Silva a , Nicola Montano b , Helio Cesar Salgado c , Rubens Fazan Ju ´ nior c, * a Department of Biological Sciences, School of Medicine of Tria ˆngulo Mineiro, Uberaba, MG Brazil b Department of Clinical Sciences, Internal Medicine II, L. Sacco Hospital, University of Milan, Milano, Italy c Department of Physiology, School of Medicine of Ribeira ˜o Preto, Av. Bandeirantes 3900, 14049-900, Ribeira ˜o Preto, SP, Brazil Received 20 July 2005; received in revised form 28 November 2005; accepted 28 November 2005 Abstract We studied the effects of chronic (4 weeks) angiotensin converting enzyme inhibition with captopril on arterial pressure (AP) and heart rate (HR) variability, as well as on cardiac baroreflex sensitivity (BRS), in aged (20 months) rats. Series of basal RR interval (RRi) and systolic AP (SAP) were studied by autoregressive spectral analysis with oscillations quantified in low (LF: 0.2 – 0.8 Hz) and high frequency (HF: 0.8 – 2.5 Hz). BRS was measured by linear regression between HR and MAP changes. Captopril did not affect the spectra of RRi or SAP in young rats. Aged rats presented a reduction in variance (time domain) and in LF and HF oscillations of RRi and SAP. Captopril induced, in aged rats, a decrease in absolute and normalized LF oscillations and in LF/HF ratio of RRi. Captopril also reduced the variance, without changing its LF or HF components of SAP. Reflex tachycardia was reduced in aged as compared to young rats (À 1.1 T 0.2 versus À 3.4 T 0.5 bpm/mm Hg) and captopril did not affect it. Reflex bradycardia was also reduced in aged rats (À 0.7 T 0.5 versus À 2.0 T 0.4 bpm/mm Hg), but captopril prevented this attenuation in aged rats (À 2.3 T 0.3 versus À 0.7 T 0.5 bpm/mm Hg). These data indicate that there is a reduction in HR and SAP variability during aging, suggesting impairment of cardiovascular autonomic control. Captopril was able to change the power of oscillatory components of RRi, suggesting a shift in cardiac sympatho/vagal balance toward parasympathetic predominance. In addition, blockage of ACE improved the reflex bradycardia, but not the reflex tachycardia in aged rats. D 2005 Elsevier B.V. All rights reserved. Keywords: Aging; Heart rate variability; Baroreceptor; ACE inhibitor; Rats 1. Introduction Aging is associated with an impairment of arterial pressure regulation which is expressed by an increased arterial pressure variability (Shi et al., 2003; Laitinen et al., 2004) and tendency to postural and postprandial hypoten- sion (Ferrari et al., 2003). In addition, it is well known that aging is associated with a reduction of heart rate variability (Ferrari et al., 2003) and depression of cardiac baroreflex sensitivity (BRS) in both humans (Gribbin et al., 1971; Jones et al., 2003) and animals (Ferrari et al., 1991; Irigoyen et al., 2000). The attenuation of baroreflex control of heart rate (HR) during aging (Gribbin et al., 1971; Ferrari et al., 1991, 2003; Sei et al., 2002; Jones et al., 2003; Nagai et al., 2003) could be involved in higher arterial pressure variability (Laitinen et al., 2004), orthostatic intolerance (Sei et al., 2002; Laitinen et al., 2004), reduced vagal control of the heart (Ferrari et al., 2003; Shi et al., 2003) and increased sympathetic nerve activity to the heart and vessels (Ferrari et al., 2003). All these alterations might be associated with electrical and morphological changes of myocardium which significantly increase the incidence of life-threatening cardiac arrhythmias and sudden death in aged subjects (Molander et al., 2003; Kistler et al., 2004; Souza Neto et al., 2004). Accordingly, therapeutic strategies which im- prove reduced heart rate variability and cardiac baroreflex 1566-0702/$ - see front matter D 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.autneu.2005.11.004 * Corresponding author. Tel.: +55 16 36023331; fax: +55 16 36330017. E-mail address: rfazanjr@rfi.fmrp.usp.br (R. Fazan Ju ´ nior). Autonomic Neuroscience: Basic and Clinical 124 (2006) 49 – 55 www.elsevier.com/locate/autneu