Aim:
To analyze the sequence of adaptive responses induced by training (T) on both hemodynamic profile and cytokines gene expression within the paraventricular nucleus (PVN).
Methods:
SHR submitted to T (treadmill, 55% maximal capacity, 1h/day, 5 d/week) or kept sedentary (S), were cannulated for measurement of pressure (BP), heart rate (HR) and baroreflex sensitivity (BrS) at rest on weeks 0, 1, 2, 4 and 8 of protocols. HR and BP variability (power spectral analysis) were also evaluated. After euthanasia, brains were removed for isolation of PVN. Total mRNA was extracted for quantification of TNFα and IL-6 expression by real time PCR (HPRT as the endogenous gene). WKY were used as time controls. One-way ANOVA, with Fisher post-hoc test and Pearson correlation were employed.
Results:
At the beginning of the protocols, SHR exhibited high mean BP and HR, decreased BrS, increased BP variability and decreased HR variability (170±3 mmHg, 356±7 b/min; 2.3±0.2 b/min/mmHg, 14±2 mmHg
2
and 14±2 ms
2
) when compared to WKY (119±2 mmHg, 307±6 b/min; 3.6±0.3 b/min/mmHg, 6±1 mmHg
2
and 22±2 ms
2
, respectively). Pro-inflammatory cytokines expression in PVN are also elevated in SHR
vs
WKY (TNF-α= 1.9±0.3
vs
1.2±0.1, IL-6= 4.9±0.8
vs
1.1±0.3 UA). In the SHR, T caused significant increases on BrS (4.0±0.2 b/min/mmHg, T
2
-T
8
), HR variability (21±1 ms
2
, with a 60% increase of HF component from T
4
-T
8
) and prevented the increase on BP variability in the SHR (13±2
vs
20±3 mmHg
2
, T
8
vs
S
8
, with 29% reduction of LF component at T
8
). T caused a prompt normalization of TNFα and IL-6 mRNA expression within the PVN (1.3±0.2 and 0.9±2 UA at T
2
), accompanied by HR reduction (338±4 b/min, T
4
-T
8
) and mean BP fall (159±6 mmHg, T
8
), with significant correlations between TNFα x HR variability (Y=-3.6x+24.3, r= -0.29; P=0.04), TNFα x BrS (Y=-0.7x+4.3, r=-0.35; P=0.01), TNFα x BP (Y=9x+140, r= 0.26; P=0.04) and TNFα x HR (Y=18x+309, r= 0.29; P=0.03). PVN IL-6 content was also correlated with HR variability (Y=-1.8x+21.5, r=-0.36; P=0.01), BrS (Y= -0.3x+4.2, r=-0.44; P<0.001) and HR (Y=7x+324, r=0.30; P=0.02).
Conclusions:
Data suggested the involvement of PVN pro-inflammatory cytokines in the mediation of cardiovascular deficits in the SHR and the efficacy of T to prompt normalize these deleterious effects.
Pro‐inflammatory cytokines increase neuronal activity in the hypothalamic paraventricular nucleus and contribute to the pathogenesis of streptozotocin‐induced diabetes
