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International Journal of Environmental Health Research

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Effects of sidestream cigarette smoke exposure on baroreflex components in spontaneously hypertensive rats

Vitor E. Valentia; Luiz Carlos Abreub; Paulo H. Saldivac; Tatiana D. Carvalhoa; Celso Ferreiraa a Departamento de Medicina, Disciplina de Cardiologia, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil b Departamento de Morfologia e Fisiologia, Faculdade de Medicina do ABC, Santo André, Brazil c Departamento de Patologia, Universidade de São Paulo, São Paulo, Brazil Online publication date: 14 December 2010

To cite this Article Valenti, Vitor E. , Abreu, Luiz Carlos , Saldiva, Paulo H. , Carvalho, Tatiana D. and Ferreira,

Celso(2010) 'Effects of sidestream cigarette smoke exposure on baroreflex components in spontaneously hypertensive rats', International Journal of Environmental Health Research, 20: 6, 431 — 437 To link to this Article: DOI: 10.1080/09603123.2010.491852 URL: http://dx.doi.org/10.1080/09603123.2010.491852

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International Journal of Environmental Health Research Vol. 20, No. 6, December 2010, 431–437

Effects of sidestream cigarette smoke exposure on baroreflex components in spontaneously hypertensive rats
Vitor E. Valentia*, Luiz Carlos Abreub, Paulo H. Saldivac, Tatiana D. Carvalhoa and Celso Ferreiraa
a Departamento de Medicina, Disciplina de Cardiologia, Universidade Federal de Sa˜o Paulo (UNIFESP), Sa˜o Paulo, Brazil; bDepartamento de Morfologia e Fisiologia, Faculdade de Medicina do ABC, Santo Andre´, Brazil; cDepartamento de Patologia, Universidade de Sa˜o Paulo, Sa˜o Paulo, Brazil

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(Received 4 September 2009; final version received 4 April 2010) We evaluated short-term effects of sidestream cigarette smoke (SSCS) exposure on baroreflex function in spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) normotensive rats. Rats were exposed to SSCS during three weeks, 180 min, five days per week, in a concentration of carbon monoxide (CO) between 100 and 300 ppm. We observed that SSCS exposure increased tachycardic peak and heart rate range while it attenuated bradycardic reflex in WKY. In respect to SHR, SSCS also increased tachycardic peak. Taken together, our data suggests that three weeks of exposure to SSCS affects the sympathetic and parasympathetic component of the baroreflex in normotensive WKY while it tended to affect the sympathetic component in SHR. Keywords: tobacco; baroreflex; air pollutants; smoke

Introduction There is growing evidence that long-term exposure to fine particulate matter air pollution contributes to the risk of all-cause and cardiovascular mortality (Pope et al. 2002). Moreover, the inspired dose of fine particles from ambient pollution is extremely small compared to that from sidestream cigarette smoke (SSCS) (Gamble and Nicolich 2000; Stinn et al. 2005; Tricker et al. 2009). A study of ambient fine particulate pollution and secondhand cigarette smoke estimates that its cardiovascular mortality effect is much higher than would be expected on the basis of effects extrapolations of active cigarette smoking that assumes a linear dose-response relationship that goes through the origin (Howard and Thun 1999). Baroreflex is one of the body’s homeostatic mechanisms to maintain blood pressure (Valenti et al. 2009a). Besides cardiac hypertrophy observed in stress models and in spontaneous hypertensive rats (SHR) (Cenko et al. 2004; Meneghini et al. 2008; Daud et al. 2009; Ferreira et al. 2009; Meneghini et al. 2009), baroreflex is also impaired in this strain (Valenti et al. 2009a). Hence, this strain is already at a higher risk due to their baroreflex impairment (Valenti et al. 2009a).

*Corresponding author. Email: valenti@unifesp.br
ISSN 0960-3123 print/ISSN 1369-1619 online Ó 2010 Taylor & Francis DOI: 10.1080/09603123.2010.491852 http://www.informaworld.com

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Although it is documented in the literature that long-term (years) exposure to both SSCS and mainstream cigarette smoke impairs baroreflex in human (Shinozaki et al. 2008), the short-term effects of SSCS on baroreflex function in SHR have not yet been demonstrated. Thus, in this study we investigated the effects of SSCS exposure on baroreflex in SHR and Wistar Kyoto (WKY) normotensive rats. Method We used WKY and SHR (15–17 weeks old). They were kept under a 12 h light/dark cycle (lights on at 07:00 h) and had free access to food and water. The Institution’s Animal Ethics Committee authorized housing conditions and experimental procedures. Rats were placed in the transparent chamber, with a volume of approximately 95 6 80 6 65 cm3, where four rats remained. The concentration of smoke carbon monoxide (CO) was maintained between 100 and 300 ppm (23 + 18C, 50–60%) (Gairola et al. 2001). Rats were exposed to SSCS (1.1 mg of nicotine, 14 mg of tar and 15 mg of carbon monoxide) during 180 min, five days/ week, for three weeks between 08:00 and 11:00 h. Control animals were maintained at the same place and the same conditions as the SSCS group but exposed to fresh air not contaminated by smoke CO. Rats were anesthetized one day before the experiments with ketamine (50 mg/kg i.p.) and xylazine (50 mg/kg i.m.) and a catheter of PE-10 polyethylene was inserted into the abdominal aorta through the femoral artery for blood pressure and heart rate recording. The catheters were tunneled under the skin and exteriorized at the animal’s dorsum. One day after surgery, animals were allowed 20 min to adapt to the conditions of the experimental room such as sound and illumination before starting blood pressure and heart rate recording. Pulsatile arterial pressure (PAP) of freely moving animals was recorded using an HP-7754A preamplifier (Hewlett Packard, USA) and an acquisition board (MP100A, Biopac Systems Inc, USA) connected to a computer. Mean arterial pressure (MAP) and heart rate (HR) values were derived from the PAP recordings and processed on-line (Valenti et al. 2009a, 2009b). The baroreflex was tested with a pressor dose of phenylephrine (PE-bolus-8 mg/kg IV; Sigma Chemical) and depressor doses of sodium nitroprusside (NaNPbolus-50 mg/kg IV; RBI). The baroreflex was calculated as the derivation of HR in function of the MAP variation (DHR/DMAP). There was an interval of at least 15 min between the infusions to allow the recovery of basal values. We also evaluated bradycardic and tachycardic peak and HR range, the difference between bradycardic and tachycardic peak. Variables calculation was performed by using the Biopac system program (MP100A, Biopac Systems Inc, USA). The delay in reflex HR responses was about 1.2 s because of the time for baroreflex synapse processing, which is 700 ms according to Su et al. (1992), and the integration factor of the recording system, which was about 500 ms (Cisternas et al. 2010; Valenti et al. 2010). The results were reported as means + standard error of means (SEM). In order to verify if SSCS exposure effects were different between two strains (WKY and SHR) we applied two-way analysis of variance (ANOVA) (strain vs. SSCS) followed by post hoc Tukey test. Differences were considered significant when the probability of a Type I error was less than 5% (p 5 0.05).

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SSCS exposure during three weeks affected tachycardic peak and HR range in WKY rats, while in SHR the tachycardic peak and HR range were altered by SSCS exposure (Table 1). In relation to bradycardic responses to intravenous PHE, WKY control rats presented the highest response, which was higher than WS, SC and SS groups. Thus, it leads us to suggest that SSCS exposure attenuated this component of the baroreflex in WKY rats (Figure 1). NaNP-induced decrease in MAP was reduced in WKY groups compared to SHR groups and tachycardic reflex responses to intravenous NaNP were enhanced in WKY groups compared to the SHR control group, but were not different in the SHR exposed to SSCS (Figure 2). Discussion
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Due the toxic effects of cigarette components (Yamasaki et al. 2009) and other pollutant agents on the cardiovascular system (Solomon et al. 2003; FukudaMatsuda et al. 2007) presented in the literature, we evaluated baroreflex function in WKY and SHR exposed to SSCS during three weeks. Our exposure protocol showed that SSCS affected bradycardic reflex, tachycardic peak and HR range in WKY rats, whereas it influenced the tachycardic peak and HR range in SHR. Maximal parasympathetic activity were not attenuated or elevated in WKY and SHR exposed to SSCS compared to age-matched control groups, while the maximal sympathetic activity was significantly increased in SHR and WKY rats exposed to SSCS. Our data support the hypothesis that less than 30 days of cigarette exposure is sufficient to change the sympathetic component of the baroreflex without change basal arterial pressure (Paiva et al. 2003). This method
Table 1. Baseline level of mean arterial pressure (MAP) and heart rate (HR), bradycardic and tachycardic peak, HR range and baroreflex gain (BG) in WKY (n ¼ 15) and SHR (n ¼ 16) exposed to SSCS and to ambient air (WKY: n ¼ 22; SHR: n ¼ 18). Mean þ SEM, maximum and minimum. Variable MAP (mmHg) HR (bpm) Bradycardic peak (bpm) Tachycardic peak (bpm) HR range (bpm) BG (bpm 6 mmHg71) PHE BG (bpm 6 mmHg71) NaNP WKY control 115.6 + 2.2 (101–124) 338.2 + 8.7 (239–378) 208.2 + 7 (160–260) 456.7 + 9 (352–500) 248.5 + 12 (149–316) 72.2 + 0.15 (71.07–3.01) 72.8 + 0.15 (71.29–3.9) WKY exposed to SSCS 108.3 + 2.3 (96–121) 320.3 + 7.9 (280–363) 226 + 8.7 (155–266) 490.1 + 6.9 (461–545)* 265.8 + 6 (229–323)*$ 71.78 + 0.15 (71.14–3.03) 73.01 + 0.15 (72.2–3.93) SHR control SHR exposed to SSCS

166.3 + 15.2 168.9 + 2 (139–194)* (160–192)* 344.8 + 6.5 350.7 + 7.5 (318–402) (297–446) 284.2 + 10 281.3 + 9.5 (211–342)* (214–352)* 443 + 7.8 487.5 + 7.6 (400–480) (444–521)*$ 158.8 + 7 202.6 + 9.8 (100–189)* (148–236)$ 70.77 + 0.11 71.03 + 0.19 (70.28–1.83)*# (70.24–2.73)*# 71.52 + 0.14 71.43 + 0.14 (70.52–2.61)*# (70.37–2.32)*#

*p 5 0.05: Different from control WKY. #p 5 0.05: Different from WKY exposed to SSCS. $p 5 0.05: Different from control SHR.

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Figure 1. Increase in mean arterial pressure (MAP, mmHg) and decrease in heart rate (HR, bpm) in response to phenylephrine (PHE, 8 mg/kg i.v.) in WKY and SHR exposed to SSCS (WS, n ¼ 15; SS, n ¼ 16, respectively) and to ambient air (WC, n ¼ 22; SC, n ¼ 18, respectively). *p 5 0.05: Different from control WKY; #p 5 0.05: Different from WKY exposed to SSCS.

to activate baroreflex is well accepted by the literature (Valenti et al. 2009a, 2009b; Cisternas et al. 2010). PHE increases arterial pressure and activates the parasympathetic component of the baroreflex, the bradycardic reflex and then calculates bradycardic baroreflex gain. NaNP reduces blood pressure and activates the sympathetic component of the baroceptor reflex (Valenti et al. 2009a, 2009b; Cisternas et al. 2010). To the best of our knowledge, no study has specifically investigated the impact of a short period of exposure to SSCS, the component usually inhaled by nonsmokers exposed to passive smoking, on baroreflex components in SHR. Apart from nicotine, cigarette smoke contains thousands of other chemical substances, including carbon monoxide, hydrogen cyanide, nitrogen oxides, aldehydes, Nnitrosamines, polyaromatic hydrocarbons (Cenko et al. 2004; Pouliou et al. 2008). SSCS has a higher concentration of toxic substances compared to mainstream smoke due to a lower temperature of combustion as well as lack of filtering. For instance, there is five times more acrolein in SSCS compared to mainstream smoke (Talbot et al. 1998).

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Figure 2. Decrease in mean arterial pressure (MAP, mmHg) and decrease in heart rate (HR, bpm) in response to sodium nitroprussied (NaNP, 50 mg/kg i.v.) in WKY and SHR exposed to SSCS (WS, n ¼ 15; SS, n ¼ 16, respectively) and to ambient air (WC, n ¼ 22; SC, n ¼ 18, respectively). *p 5 0.05: Different from control SHR; #p 5 0.05: Different from SHR exposed to SSCS.

Our results from ANOVA suggest that while in normotensive WKY rats SSCS exposure affects parasympathetic and sympathetic components of baroceptor reflex, in SHR it influences only the sympathetic component before change arterial pressure. Therefore, short-term SSCS exposure affects different components of baroreflex in WKY and SHR. In conclusion, sidestream cigarette smoke exposure over three weeks affected the sympathetic and parasympathetic component of the baroreflex in WKY while it affected the sympathetic component of the baroreflex in SHR. We believe that secondhand smoke affects the cardiovascular system firstly by changing the autonomic function. Acknowledgments We thank Mr Jason Saltsgiver for critically evaluating the English grammar. This ` research was supported by grants from Fundacao de Amparo a Pesquisa do Estado ¸ ˜ de Sao Paulo (FAPESP) (003/08). ˜

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