Hydrogen Sulfide Facilitates the Impaired Sensitivity of Carotid Sinus Baroreflex in Rats with Vascular Calcification

Abstract

Arterial baroreflex is a general mechanism maintaining cardiovascular homeostasis; its sensitivity is reduced in vascular calcification (VC). Hydrogen sulfide (H₂S) treatment facilitates baroreflexive sensitivity in normal and hypertensive rats. Here, we aimed to detect the effect of H₂S on baroreflexive sensitivity in rats with VC. The rat VC model was induced by vitamin D₃ plus nicotine for 4 weeks. The sensitivity of baroreflex was detected by perfusing the isolated carotid sinus. VC was assessed by hematoxylin and eosin (H&E) staining, Ca²⁺ content and alkaline phosphatase (ALP) activity. Protein levels were detected by western blot analysis. Vitamin D₃ plus nicotine induced structural disorder and elevated Ca²⁺ content in the aortic and carotid arterial wall and increased plasma ALP activity. In the calcified aorta and carotid artery, protein levels of contractile phenotype markers of vascular smooth muscle cells (VSMCs) were downregulated and that of osteoblast-like phenotype markers and endoplasmic reticulum stress (ERS) markers were upregulated. NaHS treatment ameliorated the histologic disorder and Ca²⁺ content in the calcified aorta and carotid artery, inhibited the elevated plasma ALP activity, and prevented the transformation of the VSMC phenotype and activation of ERS in rats with VC. Chronic NaHS treatment prevented the impairment of the baroreflex sensitivity and acute NaHS treatment dose-dependently improved the sensitivity in rats with VC. Our results suggested that H₂S could directly facilitate the impairment of baroreflex in rats with VC and ameliorate VC, which might provide new target and strategy for regulation of the baroreflex and therapy of VC.

Keywords: baroreflex; endoplasmic reticulum stress; hydrogen sulfide; perfusion of isolated carotid sinus; vascular calcification.

Figure 1

H₂S ameliorates vascular calcification (VC) detected by morphology of vascular vessels (a, aorta; b, transverse section of carotid artery; c, longitudinal section of carotid artery), calcium content in aorta (d), and carotid artery (e), and plasma alkaline phosphatase (ALP) activity (f). Data are mean ± SD. ^*P < 0.05 vs. control; ^#P < 0.05 vs. calcification (Cal) (n = 8 each group).

Figure 2

Protein expression of contractile phenotype and osteoblast-like phenotype markers of vascular smooth muscle cells in aorta (A) and carotid artery (B). Data are mean ± SD. ^*P < 0.05 vs. control; ^#P < 0.05 vs. Cal. (n = 8 each group).

Figure 3

Protein expression of endoplasmic reticulum stress markers in aorta (A) and carotid artery (B). Data are mean ± SD. ^*P < 0.05 vs. control; ^#P < 0.05 vs. Cal. (n = 8 each group).

Figure 4

The original recording images (A,D), functional curves (B,E) and peak slope (C,F) of carotid sinus baroreflex. (A–C), Effect of chronic NaHS treatment on baroreflex; (D–F), Effect of acute NaHS treatment on baroreflax. Data are mean ± SD. ^*P < 0.05 vs. control; ^#P < 0.05 vs. Cal. (n = 8 each group).