Pharmacological Effect of Hydrogen Sulfide on the Vasopressor Responses in Male Wistar Rats with Insulin Resistance
Authors: Beltran‐Ornelas Jesus Hernan , Lopez‐Muñoz Francisco Javier , Silva‐Velasco Diana Laura , Sanchez‐Lopez Araceli , de la Cruz Saul Huerta , Gomez Carolina Belen , Medina‐Terol Grecia Josefa , Centurion David 
Published: June 2021

Several lines of evidence have shown the potential role of hydrogen sulfide (H2S) in insulin resistance. However, up to date, the effect of H2S has not been evaluated in the cardiovascular alterations by fructose‐induced insulin resistance. Thus, the aim of this study was to determine the effect of NaHS (sodium hydrosulfide; H2S donor), DL‐propargylglicine (DL‐PPG; cystathionine‐Ɣ‐lyase inhibitor) and hydroxylamine (HA; cystathionine‐β‐synthase inhibitor) on the vasopressor responses induced by sympathetic stimulation (0.03–3 Hz) or by bolus injections of the noradrenaline agonists (α1/2; 0.003–3 μg/kg), methoxamine (α1; 3–100 μg/kg) and UK‐14304 (α2; 0.03–30 μg/kg) in rats with fructose‐induced insulin resistance. For this purpose, 36 rats were divided in two groups. The first group (n=30) was treated with fructose (15% in drinking water) during 20 weeks, while the second group (control; n=6) received tap water. 16 weeks after the treatment with fructose, the first group was divided in 5 subgroups (n=6 each), which received daily i.p. administration during 4 weeks with: (1) nothing; (2) phosphate buffer saline (PBS; 1 mL/g); (3) NaHS (5.6 mg/kg); (4) DL‐PPG (10 mg/kg); and (5) HA (10 mg/g). Next, oral glucose tolerance test (OGTT) and insulin levels were determined before and after administration of glucose (2 g/kg, p.o.). Finally, under anesthesia with isoflurane, animals were pithed and prepared to determine the vasopressor responses induced by stimulation of the sympathetic nervous system. Animals treated with fructose showed hyperinsulinemia, insulin resistance and hypertension. Interestingly, these parameters were reverted by HA but not by PBS. NaHS decreased blood pressure while DL‐PPG increased blood pressure and diminished HOMA‐index. In animals with insulin resistance, the vasopressor responses to sympathetic stimulation were decreased (1 and 3 Hz) while those induced by noradrenaline, methoxamine and UK 14,304 remained unchanged when they were compared with control. PBS and DL‐PPG failed to modify the vasopressor responses aforementioned. On the other hand, NaHS increased the vasopressor responses to sympathetic stimulation (3 Hz), noradrenaline (1 μg/kg) and methoxamine (30 μg/kg), but the responses to UK‐14304 was no modify. HA decreased the vasopressor responses to sympathetic stimulation (1 and 3 Hz), noradrenaline (0.1–3 μg/kg), methoxamine (30 and 100 μg/kg) and UK‐14304 (3–30 μg/kg). These results suggest that chronic treatment with NaHS, but not DL‐PPG, was able to revert the cardiovascular alterations induced by fructose‐induced insulin resistance suggesting a beneficial effect of H2S in the cardiovascular system. In contrast, HA produced: (1) a marked decreased on sympathetic function which may explain its anti‐hypertensive effect; and (2) a significant reduction on insulin resistance. These data may suggest that H2S could be implicated in the pathophysiology of the insulin resistance.

Support or Funding Information

The authors acknowledge to Conacyt (Grant No. 252702) for its financial support.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.