The Effect of High Fat Diet and H2S Donor GYY-4137 on Vascular Function in Spontaneously Hypertensive Rats

Metabolic syndrome is a growing global health burden, resulting in an urgent need for new therapeutic strategies. We evaluated the effects of 3 weeks of treatment with slow-releasing H ₂ S donor GYY-4137 on adiposity, systolic blood pressure (sBP), plasma biochemical indices, vascular function and nitric oxide (NO) and hydrogen sulfide (H ₂ S) pathways in the isolated thoracic aortas (TAs) and mesenteric arteries (MAs) from spontaneously hypertensive rats (SHRs) fed a high-fat diet (HFD) for 8 weeks. Although the HFD increased TAs relaxation, it induced cardiac remodeling, decreased adrenergic contraction, reduced NO participation in vasoactive responses, decreased NO-synthase (NOS) activity, altered the expression of the endothelial NOS (reduced), inducible NOS, and tumor necrosis factor alpha (TNFα) (both increased) proteins and increased adiposity and plasma chemerin levels. Treatment with GYY-4137 reduced sBP, improved relaxation of the MA, partially restored the contractility of the TA, generally restored NO signaling, and decreased the expression of the inducible NOS and TNFα proteins and plasma chemerin. Thus, a slow H ₂ S-releasing donor could partially ameliorate metabolic changes induced by increased fat intake during essential hypertension and trigger beneficial vasoactive effects associated with the restoration of NO signaling and suppression of inflammation.