Aging and hypertension decrease endothelial NO‐related dilating function and gamma‐glutamyl transferase activity but not S‐nitrosoglutathione‐induced aortic vasodilation. (1st February 2018)

• Record Type: Journal Article
• Authors: Perrin‐Sarrado, Caroline; Dahboul, Fatima; Leroy, Pierre; Lartaud, Isabelle
• Is Part Of: Fundamental & clinical pharmacology. Volume 32:Number 2(2018)
• Page Start: 134
• Page End: 140
• Publication Date: 2018-02-01
• Subjects: gamma‐glutamyltransferase -- NO‐dependent vasorelaxation -- S‐nitrosoglutathione -- spontaneous hypertensive rat; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/fcp.12347
• Languages: English
• ISSNs: 0767-3981

Abstract

Abstract: S ‐nitrosoglutathione (GSNO), which is involved in the transport and the storage of NO, induces vasorelaxation. It requires gamma‐glutamyl transferase (GGT), an enzyme present on the endothelium, to transfer NO into the cell. We evaluated whether aging and hypertension, which induce NO‐related dilating dysfunction, are associated with decreased vascular GGT activity and modify the vasorelaxant effect of GSNO. Thoracic aortic rings isolated from male spontaneous hypertensive rats (SHR) and Wistar‐Kyoto rats (WKY) aged 20–22 (adult) or 57–60 weeks (mature) were preconstricted with phenylephrine, then submitted to concentration‐vasorelaxant response curves (maximal response: E max ; pD2 ) to GSNO and carbachol (the latter to measure NO‐related dilating function). GGT activity was measured using chromogenic substrate. Both aging and hypertension lowered E max values for carbachol ( E max −8% in adult SHR, −42% in mature SHR vs. age‐matched WKY, p age and p hypertension < 0.05) demonstrating NO‐related dilating dysfunction. Aortic GGT activity also decreased with aging and hypertension (−22% in adult and −75%, reaching 3 nmol/min/g of tissue, in mature SHR vs. 12 in age‐matched WKY and 23 in adult WKY, p age and p hypertension < 0.05). The pD2 values of GSNO were similar in mature SHR and WKY but higher in adult SHR ( p interaction < 0.05). Aging in hypertensive rats decreased NO‐related vasorelaxant function and vascular GGT activity, but did not lower the vasorelaxant response to GSNO. This opens perspectives for GSNO‐based therapeutics restoring nitric oxide bioavailability and vascular protection in a context of endothelial dysfunction.