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Tranilast treats cold-related hypertension by reducing the expression of NLRP3 inflammasome
doi: 10.2478/fzm-2021-0012
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Abstract:
Objective: Cold exposure is associated with increased prevalence of hypertension and the related severe cardiovascular events. Aberrant activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays an important role in the development of hypertension. Tranilast (TR), an inhibitor of NLRP3, provides a useful pharmacological probe for exploring the role of NLRP3 in pathogenesis associated with inflammation and its potential application as a therapeutic agent. This study was designed to examine the effects of TR on NLRP3 and hypertension in rats exposed to cold environment to simulate the frigid-zone conditions. Methods and results: Sprague Dawley (SD) rats were exposed to moderate cold temperature (4±1℃), and then were randomized to receive TR or vehicle for 3 weeks, while the control group was raised under rat room temperature (RT, 23±1℃). We found that cold exposure substantially increased blood pressure, NLRP3 inflammasome level, and fibrosis in aorta, which were reversed by TR. Conclusion: TR has an anti-hypertensive property in cold environment, and this beneficial action is likely conferred by its inhibitory effects on inflammation and fibrosis. These findings suggest TR as a potential drug for the treatment of cold-induced hypertension.
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Key words:
- cold exposure /
- blood pressure /
- NLRP3 /
- tranilast
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Figure 1. Cold exposure increases blood pressure in rats.
(A and B) SDP and DBP change among the groups. P < 0.0001, P = 0.0258 vs. RT group, n = 10 per group. RT, room temperature.
Figure 2. Cold exposure increases blood pressure in rats by activating the NLRP3 inflammasome.
(A and B) Western blotting for NLRP3, ASC and Casp1-p20 proteins in aorta isolated from rats in the RT and cold groups. P = 0.031 3, P = 0.012 6 vs. RT group, n = 10 per group. RT, room temperature. (C and D) ELISA for the plasma levels of IL-1β and IL-18 in the RT and cold groups. P = 0.023 8, P = 0.019 4 vs. RT group, n = 10 per group.
Figure 3. Tranilast decreases blood pressure in cold exposed rats.
(A and B) Comparisons of SDP and DBP values between cold exposed rats with and without tranilast treatment. P < 0.000 1 vs. cold group, n = 10 per group. TR, tranilast.
Figure 4. Tranilast reduces the expression of NLRP3 inflammasome induced by cold exposure.
(A and B) Western blot results for NLRP3, ASC and Casp1-p20 proteins of aorta in the cold and cold + TR groups. P = 0.002 2, P = 0.002 2 vs. cold group, n = 10 per group. TR, tranilast.
Figure 5. Tranilast alleviates aortic fibrosis in cold exposed rats.
(A) Hematoxylin and eosin (H & E) staining (200× magnification; scale bar: 50 μm. (B) Masson's trichrome staining (200× magnification; scale bar: 50 μm). (C) Collagen volume fraction (CVF) per field in the atria of rats from each group. TR, tranilast.
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