NaHS restores the vascular alterations in the renin-angiotensin system induced by hyperglycemia in rats

Abstract

Hyperglycemia (HG) impairs the renin-angiotensin system (RAS), which may contribute to vascular dysfunction. Besides, hydrogen sulfide (H₂S) exerts beneficial cardiovascular effects in metabolic diseases. Therefore, our study aimed to determine the effects of chronic administration of sodium hydrosulfide (NaHS; inorganic H₂S donor) and DL-Propargylglycine [DL-PAG; cystathionine-ץ-lyase (CSE) inhibitor] on the RAS-mediated vascular responses impairments observed in thoracic aortas from male diabetic Wistar rats. For that purpose, neonatal rats were divided into two groups that received: 1) citrate buffer (n = 12) or 2) streptozotocin (STZ, 70 mg/kg; n = 48) on the third postnatal day. After 12 weeks, diabetic animals were divided into 4 subgroups (n = 12 each) that received daily i.p. injections during 4 weeks of: 1) non-treatment; 2) vehicle (PBS, 1 mL/kg); 3) NaHS (5.6 mg/kg); and 4) DL-PAG (10 mg/kg). After treatments (16 weeks), blood glucose, angiotensin-(1-7) [Ang-(1-7)], and angiotensin II (Ang II) levels, vascular responses to Ang-(1-7) and Ang II, and the expression of angiotensin AT₁, AT₂, and Mas receptors, angiotensin converting enzyme (ACE) and ACE type 2 (ACE2) were determined. HG induced: 1) increased blood glucose levels and expression of angiotensin II AT₁ receptor; 2) impaired Ang-(1-7) and Ang II mediated vascular responses; 3) decreased angiotensin levels and expression of angiotensin II AT₂ and angiotensin-(1-7) Mas receptors, and ACE2; and 4) no changes in ACE expression. Interestingly, NaHS, but not DL-PAG, reversed HG-induced impairments, except for blood glucose level changes. These results suggest that NaHS restores vascular function in streptozotocin-induced HG through RAS modulation.

Keywords: Angiotensin receptors; Hydrogen sulfide; Hyperglycemia; Renin-Angiotensin System; Vascular dysfunction.