Captopril Partially Decreases the Effect of H2S on Rat Blood Pressure and Inhibits H2S-Induced Nitric Oxide Release From S-Nitrosoglutathione

Abstract

We studied the effects of the H 2 S donor Na 2 S on the mean arterial blood pressure (MAP) and heart and breathing rates of anesthetized Wistar rats in the presence and absence of captopril. Bolus administration of Na 2 S (1-4 µmol/kg) into the right jugular vein transiently decreased heart and increased breathing rates; at 8-30 µmol/kg, Na 2 S had a biphasic effect, transiently decreasing and increasing MAP, while transiently decreasing heart rate and increasing and decreasing breathing rate. These results may indicate independent mechanisms by which H 2 S influences MAP and heart and breathing rates. The effect of Na 2 S in decreasing MAP was less pronounced in the presence of captopril (2 µmol/l), which may indicate that the renin-angiotensin system is partially involved in the Na 2 S effect. Captoprildecreased H 2 S-induced NO release from S-nitrosoglutathione, which may be related to some biological activities of H 2 S. These results contribute to the understanding of the effects of H 2 S on the cardiovascular system.

The Role of Hydrogen Sulphide in Blood Pressure Regulation

“…Slow H 2 S-donor AP39 decreased and consequently increased blood pressure at 0.2-1.0 µmol/kg . Our in vivo experiments showed that intravenously injected Na 2 S (3 μmol/kg) had vasopressor effects only; however, at higher Na 2 S doses (8-30 μmol/kg), we demonstrated a transient biphasic effect on blood pressure (Drobna et al 2015). The K ATP channel has been reported to be a major molecular target of the vasorelaxant and vasodepressor effects of H 2 S (Zhao et al 2001).…”

“…We confirmed this finding using glibenclamide, a K ATP channel inhibitor. Specifically, this inhibitor blocked the vasorelaxation induced by higher doses of H 2 S (Drobna et al 2015). Given that 1) acute pretreatment with glibenclamide did not affect low-dose H 2 S-induced contractile responses of isolated thoracic aortas and 2) the increase in blood pressure was observed at lower H 2 S concentrations than the biphasic effects, we concluded that K ATP channels were not involved in the transient blood pressure increase.…”

“…We observed that a bolus administration of captopril (an angiotensin-converting enzyme inhibitor) in vivo reduced the H 2 S donor-induced decrease in blood pressure. This result suggests that captopril might inhibit the mechanism responsible for the depressor effect of H 2 S (Drobna et al 2015). We suggested that captopril disabled the inhibitory effect of H 2 S on RAS, thereby masking the depressor effects of H 2 S. As acetylcholine decreased blood pressure to the same extent as before captopril treatment, we assumed that a change in the blood pressure baseline after captopril administration was not responsible for the weaker H 2 S effect.…”

“…Higher concentrations of H 2 S (sodium disulphide (NaHS): 2.8 and 14 µmol/kg; 0.1-1 mmol/l) evoked decrease of blood pressure or vasorelaxation in some types of isolated vessels (Zhao et al 2001, Zhao andWang 2002). Lower concentrations of H 2 S (Na 2 S: 3 µmol/kg; 10-100 µmol/l) resulted in blood pressure increase and vasoconstriction of the same vessels (Kubo et al 2007, Lim et al 2008, Drobna et al 2015.…”

“…NO and CO act via binding to the heme moiety at the active site of guanylate cyclase. H 2 S acts in part by opening ATP-sensitive potassium channels (K ATP ) on the vascular smooth muscle cells (Zhao et al 2001, Zhao and Wang 2002, Drobna et al 2015 and in part by stimulating endothelium-derived NO production (Zhao and Wang 2002). Although gaseous transmitters operate in distinct ways, studies have revealed that they can act cooperatively.…”