Modulation of tyrosine hydroxylase, neuropeptide y, glutamate, and substance p in Ganglia and brain areas involved in cardiovascular control after chronic exposure to nicotine

Abstract

Considering that nicotine instantly interacts with central and peripheral nervous systems promoting cardiovascular effects after tobacco smoking, we evaluated the modulation of glutamate, tyrosine hydroxylase (TH), neuropeptide Y (NPY), and substance P (SP) in nodose/petrosal and superior cervical ganglia, as well as TH and NPY in nucleus tractus solitarii (NTS) and hypothalamic paraventricular nucleus (PVN) of normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) after 8 weeks of nicotine exposure. Immunohistochemical and in situ hybridization data demonstrated increased expression of TH in brain and ganglia related to blood pressure control, preferentially in SHR, after nicotine exposure. The alkaloid also increased NPY immunoreactivity in ganglia, NTS, and PVN of SHR, in spite of decreasing its receptor (NPY1R) binding in NTS of both strains. Nicotine increased SP and glutamate in ganglia. In summary, nicotine positively modulated the studied variables in ganglia while its central effects were mainly constrained to SHR.

Figure 1

Immunoreactivity of tyrosine hydroxylase, neuropeptide Y, glutamate, and substance P in nodose/petrosal ganglia of Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats exposed either to nicotine or placebo delivered through subcutaneously implanted pellets during 8 weeks. Values are presented as mean ± SD, *P < 0.05 as compared to the same strain placebo treated rat; ^#P < 0.05 as compared to WKY on the same experimental condition, according to 2-way ANOVA followed by Bonferroni posttest, n = 6.

Figure 2

Immunoreactivity of tyrosine hydroxylase, neuropeptide Y, and substance P in superior cervical ganglion (SCG) of Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats exposed either to nicotine or placebo delivered through subcutaneously implanted pellets during 8 weeks. Values are presented as mean ± SD, *P < 0.05 as compared to the same strain placebo treated rat; ^#P < 0.05 as compared to WKY on the same experimental condition, according to 2-way ANOVA followed by Bonferroni posttest, n = 6.

Figure 3

Immunoreactivity and mRNA expression of tyrosine hydroxylase in the nucleus tractus solitarii (NTS) and paraventricular hypothalamic nucleus (PVN) of Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats exposed either to nicotine or placebo delivered through subcutaneously implanted pellets during 8 weeks. Values are presented as mean ± SD, *P < 0.05 as compared to the same strain placebo-treated rat; ^#P < 0.05 as compared to WKY on the same experimental condition, according to 2-way ANOVA followed by Bonferroni posttest, n = 6.

Figure 4

Neuropeptide Y immunoreactivity and NPY1R binding in the nucleus tractus solitarii (NTS) and paraventricular hypothalamic nucleus (PVN) of Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats exposed either to nicotine or placebo delivered through subcutaneously implanted pellets during 8 weeks. Values are presented as mean ± SD, *P < 0.05 as compared to the same strain placebo-treated rat; ^#P < 0.05 as compared to WKY on the same experimental condition, according to 2-way ANOVA followed by Bonferroni posttest, n = 6.