Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, C011

Oral Communications

Different low-level lead exposure profiles induce long-lasting physiological changes

L. Shvachiy1, V. Geraldes1,2, Â. R. Leal1, I. Rocha1,2

1. Cardiovascular Center of University of Lisbon, University of Lisbon, Lisbon, Portugal. 2. Institute of Physiology, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.

Lead (Pb) is a toxic metal, and its widespread use has resulted in environmental contamination and significant public health problems. Exposures to lead during developmental phases can alter the normal course of development, with lifelong health consequences. Permanent Pb exposure leads to behavioural changes, cognitive impairment, sympathoexcitation, tachycardia, hypertension and autonomic dysfunction. However, the effects of an intermittent Pb exposure, increased in the past years, have not been studied. We aimed to describe Pb health effects along various profiles of exposure, including a new animal model of intermittent low-level lead exposure. For that, the tap water of seven-day pregnant Wistar females was replaced by 0.2% (p/v) lead acetate solution. After being weaned at 21 days, rat pups, both sexes, were divided into 3 groups of lead exposure (n=10/group/timepoint): long-term - PbP (exposure from foetal period until 28 weeks of age), short-term - PbS (exposure from foetal period until 12 weeks) and intermittent - PbI (exposure from foetal period until 12 weeks, lead-free period until 20 weeks and a second exposure between 20 and 28 weeks of age). At 12, 20 and 28 weeks of age, animals were anaesthetised with sodium pentobarbital solution (60mg/kg, ip) and maintained by 20% (v/v) anaesthetic solution. Blood pressure (BP), electrocardiogram, heart rate (HR) and respiratory frequency (RF) were recorded. Baro and chemoreceptor reflexes were stimulated by phenylephrine (0.2ml, 25µg/mL, iv) and lobeline (0.2ml, 25µg/mL, ia) injections, respectively, and baroreflex gain and chemoreflex sensitivity calculated. Low frequencies (LF) and high frequencies (HF) were determined for sympathetic and parasympathetic activity estimation. An age- and sex-matched control group was also used (n=10/timepoint). One-way ANOVA was used (significance p < 0.05) for statistical analysis. Our data showed a clear association between lead exposure, hypertension and baro and chemoreflexes impairment, RF increase, without HR changes. At 28 weeks, PbI group showed a less pronounced hypertension when compared to PbP group. Moreover, we showed that only a longer lead-free period is capable to reverse baroreflex impairment (PbS), without significant changes in chemoreflex function. Regarding the autonomic data, the overactivity of the sympathetic nervous system, evaluated by LF band, was concomitant with baroreceptor reflex impairment and/or hypertension in all groups. Nevertheless, a lead-free period of 8 weeks was sufficient to restore sympathetic activity toward LF values obtained in healthy control rats. In summary, this study brings new insights on the environmental factors that influence nervous and cardiovascular systems during development, which can help create public policy strategies to prevent and control the adverse effects of Pb toxicity.

Where applicable, experiments conform with Society ethical requirements