Region-Specific and Pregnancy-Enhanced Vasodilator Effects of Hydrogen Sulfide

Abstract

Hydrogen sulfide (H₂S) is a cardiovascular signaling molecule that causes vasodilation in vascular smooth muscle cells, but its mechanism is unclear. We examined how H₂S affects mesenteric and uterine arteries without endothelium in nonpregnant and pregnant rats and the underlying mechanisms. H₂S donors GYY4137 and NaHS relaxed uterine arteries more than mesenteric arteries in both pregnant and nonpregnant rats. GYY4137 and NaHS caused greater relaxation in the uterine artery of pregnant versus nonpregnant rats. High extracellular K⁺ abolished NaHS relaxation in pregnant uterine arteries, indicating potassium channel involvement. NaHS relaxation was unaffected by voltage-gated potassium channel blockers, reduced by ATP-sensitive potassium channel blockers, and abolished by calcium-activated potassium (BK_Ca) channel blockers. Thiol-reductant dithiothreitol also prevented NaHS relaxation. Thus, H₂S has region-specific and pregnancy-enhanced vasodilator effects in the uterine arteries, mainly mediated by BK_Ca channels and sulfhydration.

Keywords: H2S; artery; potassium channels; pregnant; vasodilation.

Figure 1:

GYY4137 and NaHS-induced concentration-dependent relaxation responses in nonpregnant and pregnant rat mesenteric and uterine arterial rings pre-constricted with PE. The vertical bar represents mean ± S.E.M. (n= 6, *p < 0.05 UA vs. MA). MA – Mesenteric artery; UA – Uterine artery.

Figure 2:

NaHS-induced concentration-dependent relaxation in pregnant rat uterine arterial rings in the presence and absence of high extracellular potassium concentration (80 mM). The vertical bar represents mean ± S.E.M. (n= 6, *p < 0.05 compared to control).

Figure 3:

NaHS-induced concentration-dependent relaxation in pregnant rat uterine arterial rings pre-incubated with (A) 4-aminopyridine (1 mM), (B) Glibenclamide (10 μM) and (C) iberiotoxin (100 nM) plus apamin (100 nM) for 20 min and then pre-constricted with PE. The vertical bar represents mean ± S.E.M. (n= 6, *p < 0.05 compared to control).

Figure 4:

NaHS-induced concentration-dependent relaxation in pregnant rat uterine arterial rings was pre-incubated with dithiothreitol (DTT, 2 mM) for 20 min and then pre-constricted with PE. The vertical bar represents mean ± S.E.M. (n= 6, *p < 0.05 compared to control).