Journal of APPLIED BIOMEDICINE
ISSN 1214-0287 (on-line)
ISSN 1214-021X (printed)

Volume 7 (2009), No 3, p 123-131




The effect of S-nitrosocaptopril and S-nitroso-N-acetyl-D,L- penicillamine on blood glucose concentration and haemodynamic parameters

Sacha Campbell, Ruby Alexander-Lindo, Tara Dasgupta, Donovan McGrowder

Address: Donovan McGrowder, Department of Pathology, Faculty of Medical Sciences, University of the West Indies, Mona Campus, Kingston, Jamaica
dmcgrowd@yahoo.com

Received 8th January 2009.
Revised 11th June 2009.
Published online 8th July 2009.

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SUMMARY
Studies have shown that S-nitrosothiols (RSNOs) are able to affect glucose metabolism and blood pressure in animal models. This paper describes an investigation into the effect of two RSNOs, S-nitrosocaptopril (CapSNO) and S-nitroso-N-acetyl-D,L-penicillamine (SNAP) on fasting and postprandial blood glucose concentration, and systolic and diastolic blood pressures. Rats administered intravenously with CapSNO and SNAP, using dosages of 2.0, 5.0 and 12.5 mg/kg BW, showed a dose-dependent hyperglycaemic effect. Intravenous administration of 12.5 mg/kg BW of CapSNO and SNAP caused a statistically significant increase in fasting blood glucose concentration compared to rats treated with the same dosage of captopril. SNAP-treated rats showed a significantly greater elevation of fasting (F2) blood glucose concentration (5.91 ± 0.27 mmol/l) compared to CapSNO-treated rats (5.11 ± 0.08 mmol/l. However there was no significant difference in postprandial blood glucose concentrations. SNAP, CapSNO and captopril significantly reduced both systolic and diastolic blood pressures. This was accompanied by an increase in heart rate. The anti-hypertensive property of CapSNO and SNAP was more significant than that of captopril. CapSNO was more potent than SNAP in reducing blood pressure, suggesting that CapSNO may act via a combined mechanism that involves ACE inhibition and NO release.

KEY WORDS
S-nitrosothiols; S-nitroso-N-acetylpenicillamine; S-nitrosocaptopril; hyperglycaemia; haemodynamic parameters


REFERENCES
Aquart DV, Dasgupta TP: Dynamic interaction of vitamin C with some potent nitrovasodilators, SNAP and SNOCap, in aqueous solution. Biophys Chem 107:117-131, 2004.

Askew SC, Barnett DJ, McAninly J, Williams DLH: Catalysis by Cu2+ of nitric oxide release from S-nitrosothiols (RSNO). J Chem Soc Perkin Trans 2:741-745, 1995.

Cooke JF, Andon N, Loscalzo J: S-nitrosocaptopril II. Effects on vascular reactivity. J Pharmacol Exp Ther 249:730-734, 1989.

Craven PA, DeRubertis FR: Requirement for heme in the activation of purified guanylate cyclase by nitric oxide. Biochim Biophys Acta 745:310-321, 1983.

Euser AG, Cipolla MJ: Cerebral blood flow autoregulation and edema formation during pregnancy in anesthetized rats. Hypertension 49:334-340, 2007.

Feelisch M, Kelm M: Biotransformation of organic nitrates to nitric oxide by vascular smooth muscle and endothelial cells. Biochem Biophys Res Commun 180:286-293, 1991.

Henry PJ, Drummer, OH, Horwitz PJ: S-nitrosothiols: Implications regarding tolerance to nitric oxide-containing vasodilators. Br J Pharmacol 98:757-766, 1989a.

Henry PJ, Horwitz PJ, Louis WJ: Determinants of in vitro nitroglycerin tolerance induction and reversal: influence of dose regimen nitrate-free period, and sulfurhydryl supplementation. J Cardiovasc Pharmacol 14:31-37, 1989b.

Henry PJ, Horwitz PJ, Louis WJ: Nitroglycerin induced tolerance affects multiple sites in the organic nitrate bioconversion cascade. J Pharmacol Exp Ther 248:762-768, 1989c.

Ignarro LJ, Kadowitz PJ: The pharmacological and physiological role of cyclic GMP in vascular smooth muscle relaxation. Annu Rev Pharmacol Toxicol 25:171-191, 1985.

Ignarro L, Lippton H, Edwards JC, Baricos WH, Hyman AC, Kodowitz PJ, Gruetter CA: Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: evidence for the involvement of S-nitrosothiols as active intermediates. J Pharmacol Exp Ther 218:739-749, 1981.

Ignarro LJ, Cirino G, Casini A, Napoli C: Nitric oxide as a signaling molecule in the vascular system: an overview. J Cardiovasc Pharmacol 34:879-886, 1999.

Jia L, Wong H: In vitro and in vivo assessment of cellular permeability and pharmacodynamics of S-nitrosylated captopril, a nitric oxide donor. J Pharmacol 134:1697-1704, 2001.

Keeble JE, Moore PK: Pharmacological and potential therapeutic applications of nitric oxide-releasing non-steroidal anti-inflammatory and related nitric oxide-donating drugs. Br J Pharmacol 137:295-310, 2002.

Langford EJ, Brown AS, Wainwright RJ, de Belder AJ, Thomas MR, Smith RE, Radomski MW, Martin JF, Moncada S: Inhibition of platelet activity by S-nitrosoglutathione during coronary angioplasty. Lancet 344:1458-1460, 1994.

Liu Z, Rudd MA, Freedman JE, Loscalzo J: S-transnitrosation reactions are involved in the metabolic fate and biological actions of nitric oxide. J Pharmacol Exp Ther 284:526-534, 1998.

Loscalzo J, Smick D, Andon N, Cooke J: S-nitrosocaptopril. I. Molecular characterization and effects on the vasculature and on platelets. J Pharmacol Exp Ther 249:726-729, 1989.

Matthew WR, Kerr SW: Biological activity of S-nitrosothiols: the role of nitric oxide. J Pharmacol Exp Ther 267:1529-1537, 1993.

McGrowder D, Ragoobirsingh D, Dasgupta T: The hypergycaemic effect of S-nitrosoglutathione in the dog. Nitric Oxide 3:481-491, 1999.

McGrowder D, Ragoobirsingh D, Dasgupta T: Effects of S-nitroso-N-acetylpenicillamine administration on glucose tolerance and plasma levels of insulin and glucagon in the dog. Nitric Oxide 5:402-412, 2001.

McGrowder D, Ragoobirsingh D, Dasgupta T: The effect of captopril on blood glucose, plasma insulin and blood pressure via a nitric oxide mechanism in an animal model. Diabetol Croat 32:125-131, 2003.

Megson IL: Nitric oxide donor drugs. Drugs Future 25:701-715, 2000.

Mohr S, Stamler JS, Brune B: Posttranslational modification of glyceraldehyde-3-phosphate dehydrogenase by S-nitrosylation and subsequent NADH attachment. J Biol Chem 271:4209-4214, 1996.

Moro MA, Darley-Usmar VM, Lizasoain I, Su Y, Knowles RG, Radomski MW, Moncada S: The formation of nitric oxide donors from peroxynitrite. Br J Pharmacol 166:1999-2004, 1995.

Moynihan HA, Roberts SM: Preparation of some novel S-nitroso compounds as potential slow-release agents of nitric oxide in vivo. J Chem Soc Perkin Trans 1:797-804, 1994.

Myers PR, Minor RL Jr., Guerra R Jr., Bates JN, Harrison DG: Vasorelaxant properties of the endothelium-derived relaxing factor closely resemble S-nitrosocysteine than nitric oxide. Nature 345:161-163, 1990.

Nakae I, Takahashi M, Kinoshita T, Matsumoto T, Kinoshita M: The effects of S-nitrosocaptopril on canine coronary circulation. J Pharmacol Exp Ther 274:40-46, 1995.

Needleman P, Johnson ME Jr.: Mechanism of tolerance development to organic nitrates. J Pharmacol Exp Ther 184:709-715, 1973.

Park A, Suzuki Y: Effects of intermittent hypoxia on oxidative stress-induced myocardial damage in mice. J Appl Physiol 102:1806-1814, 2007.

Salehi A, Carlberg M, Henningson R, Lundquist I: Islet constitutive nitric oxide synthase: biochemical determination and regulatory function. Am J Physiol Cell Physiol 270:C11634-C11641, 1996.

Shaffer JE, Lee F, Thomson S, Han B, Cooke JP, Loscalzo J: The haemodynamic effects of S-nitrosocaptopril in anaesthetized dogs. J Pharmacol Exp Ther 256:704-709, 1991.

Singh SP, Wishnok JS, Keshive M, Deen WM, Tannenbaum SR: The chemistry of the S-nitrosoglutathione/glutathione system. Proc Natl Acad Sci U S A 93:14428-14433, 1996b.

Singh RJ, Hogg N, Joseph J, Kalyanaraman B: Mechanism of nitric oxide release from S-nitrosothiols. J Biol Chem 271:18596-18603, 1996a.

Smith JN, Dasgupta T: Kinetics and mechanism of the decomposition of S-nitrosoglutathione by L-ascorbic acid and copper ions in aqueous solution to produce nitric oxide. Nitric Oxide 4:57-66, 2000.

Smith RP, Kruszyna H: Nitroprusside produces cyanide poisoning via a reaction with haemoglobin. J Pharmacol Exp Ther 101:557-563, 1974.

Tsikas D, Sandmann J, Rossa S, Gutzki F-M, Frolich JC: Investigations of S-transnitrosylation reactions between low-and-high molecular weight S-nitroso compounds and their thiols by high performance liquid-chromatography and gas chromatography-mass spectrometer. Anal Biochem 270:231-241, 1999.

Van der Vliet A, Hoen PA, Wong PS, Bast A, Cross CE: Formation of S-nitrosothiols via direct nitrosation of thiols by peroxynitrite with elimination of hydrogen peroxide. J Biol Chem 273:30255-30262, 1998.

Winocour P, Waldek S, Anderson DC: Captopril and blood glucose. Lancet 2:461, 1986.
CITED

Li HP, Zhang JJ, Qin L, Zhao MD. Synthesis and characterization of captopril derivatives. Res Chem Intermed. 39: 621-629, 2013.

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