Role of Plasma S-Nitrosothiols in Regulation of Blood Pressure in Anesthetized Rabbits with Special References to Hypotensive Effects of Acetylcholine and Nitrovasodilators

Ishibashi, Takaharu; Miwa, Tomoko; Nishizawa, Naoki; Shinkawa, Ikumi; Yoshida, Junko; Kawada, Toru; Nishio, Matomo

doi:10.1248/bpb.34.1307

Cited by 4 publications

(6 citation statements)

References 58 publications

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“…However, nitroglycerin presents the adverse effect of tolerance that results in a decline in its therapeutic efficacy in the course of treatment and SNP presents cytotoxicity to vascular smooth muscle cells due to cyanide release. In addition, the hypotensive effects induced by nitroglycerin and SNP are not accompanied by plasma nitrosothiol formation, 30 which could explain their short-time effect. Therefore, the longlasting hypotensive effect induced by TERPY could be related to the slow release of NO, which can be an interesting characteristic of TERPY as a potential therapeutic vasodilator.…”

Section: Discussionmentioning

confidence: 99%

Long-lasting Hypotensive Effect in Renal Hypertensive Rats Induced by Nitric Oxide Released From a Ruthenium Complex

Rodrigues¹,

Pereira

Vercesi

et al. 2012

Journal of Cardiovascular Pharmacology

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In this study, we investigated the effect of the ruthenium complex [Ru(terpy)(bdq)NO] (TERPY) on the arterial pressure from renal hypertensive 2 kidney-1 clip (2K-1C) rats, which was compared with sodium nitroprusside (SNP). The most interesting finding was that the intravenous bolus injection of TERPY (2.5, 5.0, 7 mg/kg) had a dose-dependent hypotensive effect only in 2K-1C rats. On the other hand, SNP (35 and 70 μg/kg) presented a similar hypotensive effect in both normotensive (2K) and 2K-1C although the effect of 70 μg/kg was >35 μg/kg. The injection of the nonselective NO-synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) increased the arterial pressure in 2K and 2K-1C rats with a similar magnitude. After infusion of L-NAME, the hypotensive effect induced by TERPY and SNP was potentiated in both 2K and in 2K-1C rats. The administration of the superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl increased the hypotensive effect induced by TERPY or SNP in both 2K and 2K-1C rats. The hypotensive effect induced by TERPY was longer than that produced by SNP. Taken together, our results show that the TERPY has a long-lasting hypotensive effect, which has a dose dependence and higher magnitude in 2K-1C compared with in 2K rats. In comparison with SNP, TERPY is less potent in inducing arterial pressure fall, but it presents a much longer hypotensive effect.

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Section: Discussionmentioning

confidence: 99%

Long-lasting Hypotensive Effect in Renal Hypertensive Rats Induced by Nitric Oxide Released From a Ruthenium Complex

Rodrigues¹,

Pereira

Vercesi

et al. 2012

Journal of Cardiovascular Pharmacology

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“…S ‐nitrosoglutathione (GSNO), the nitrosated form of glutathione, is an endogenous low molecular weight S ‐nitrosothiol involved in the storage and transport of NO. Several studies reported the vasorelaxant properties and/or hypotensive effects of GSNO , as its protective effects against platelet aggregation . GSNO is an interesting candidate for therapeutics as it mimics endogenous GSNO‐related functions.…”

Section: Introductionmentioning

confidence: 99%

Aging and hypertension decrease endothelial NO‐related dilating function and gamma‐glutamyl transferase activity but not S‐nitrosoglutathione‐induced aortic vasodilation

Perrin-Sarrado

Dahboul

Leroy

et al. 2018

Fundamemntal Clinical Pharma

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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 ; pD ) 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 values for carbachol (E -8% in adult SHR, -42% in mature SHR vs. age-matched WKY, p and p < 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 and p < 0.05). The pD values of GSNO were similar in mature SHR and WKY but higher in adult SHR (p < 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.

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“…We have previously documented that endothelial GGT is critical for GSNO-dependent NO-delivery and vasorelaxation in aortic rings isolated from normotensive rats (Dahboul et al, 2012). In this context, GSNO and its cellular metabolism enzymes are likely to be involved in blood pressure regulation (Ishibashi et al, 2011). …”

Section: Introductionmentioning

confidence: 99%

Reduced Activity of the Aortic Gamma-Glutamyltransferase Does Not Decrease S-Nitrosoglutathione Induced Vasorelaxation of Rat Aortic Rings

et al. 2016

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Aims: Gamma-glutamyl transferase (GGT), an enzyme present on the endothelium, is involved in the release of nitric oxide (NO) from S-nitrosoglutathione (GSNO) and in the GSNO-induced vasodilation. Endogenous GSNO is a physiological storage form of NO in tissues while exogenous GSNO is an interesting candidate for compensating for the decreased NO bioavailability occurring during cardiovascular diseases. We investigated in a rat model of human hypertension, the spontaneous hypertensive rat (SHR), submitted or not to high salt diet, whether a decreased vascular GGT activity modifies the vasorelaxant effect of GSNO.Methods: Thoracic aortic rings isolated from male SHR and Wistar Kyoto rats (WKY) aged 20–22 weeks—submitted or not for 8 weeks to a high salt diet (1% w/v NaCl in drinking water) were pre-constricted with phenylephrine then submitted to concentration-vasorelaxant response curves (maximal response: Emax; pD2) to carbachol or sodium nitroprusside to evaluate endothelial dependent or independent NO-induced vasodilation, or GSNO (exogenous NO vasodilation depending from the endothelial GGT activity). GGT activity was measured using a chromogenic substrate in aortic homogenates. Its role in GSNO-induced relaxation was assessed following inhibition of the enzyme activity (serine-borate complex). That of protein disulfide isomerase (PDI), another redox sensitive enzyme involved in GSNO metabolism, was assessed following inhibition with bacitracin.Results: Aortic GGT activity (18–23 μmol/min/mg of tissue in adult WKY) decreased by 33% in SHR and 45% in SHR with high salt diet. Emax and pD2 for sodium nitroprusside were similar in all groups. Emax for carbachol decreased by −14%, reflecting slight endothelial NO-dependent dysfunction. The GSNO curve was slightly shifted to the left in SHR and in SHR with high salt diet, showing a small enhanced sensitivity to GSNO. Involvements of GGT, as that of PDI, in the GSNO effects were similar in all groups (pD2 for GSNO −0.5 to −1.5 following enzymatic inhibition).Conclusion: Hypertension is associated with a decreased aortic GGT activity without decreasing the vasorelaxant effects of GSNO, whose bioactivity may be supplemented through the alternative enzymatic activity of PDI.

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Role of Plasma S-Nitrosothiols in Regulation of Blood Pressure in Anesthetized Rabbits with Special References to Hypotensive Effects of Acetylcholine and Nitrovasodilators

Cited by 4 publications

References 58 publications

Long-lasting Hypotensive Effect in Renal Hypertensive Rats Induced by Nitric Oxide Released From a Ruthenium Complex

Long-lasting Hypotensive Effect in Renal Hypertensive Rats Induced by Nitric Oxide Released From a Ruthenium Complex

Aging and hypertension decrease endothelial NO‐related dilating function and gamma‐glutamyl transferase activity but not S‐nitrosoglutathione‐induced aortic vasodilation

Reduced Activity of the Aortic Gamma-Glutamyltransferase Does Not Decrease S-Nitrosoglutathione Induced Vasorelaxation of Rat Aortic Rings

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