Effects of poly(ADP-ribose) polymerase inhibition on dysfunction of non-adrenergic non-cholinergic neurotransmission in gastric fundus in diabetic rats

Nitric Oxide : Biology and Chemistry
T Michael GibsonN E Cameron

Abstract

Diabetes mellitus compromises nitric oxide (NO)-mediated endothelium-dependent relaxation of blood vessels, which has been linked to the excessive generation of reactive oxygen species. There are also deleterious effect on nitrergic innervation, contributing to autonomic neuropathy symptoms such as impotence and gastroporesis. Poly(ADP-ribose) polymerase (PARP) is a nuclear protein stimulated by DNA damage, caused, for example, by oxidative stress. Activation has been linked to impaired endothelial nitric oxide synthase (eNOS)-mediated vasodilation in experimental diabetes. There is no information on the potential role of PARP in nitrergic nerve dysfunction, therefore, the aim was to examine the effects of PARP inhibition, using 3-aminobenzamide (3-AB) on neurally mediated gastric fundus relaxation in streptozotocin-induced diabetic rats. Eight weeks of diabetes caused a 42.5% deficit in maximum relaxation of in vitro gastric fundus strips to electrical stimulation of the non-adrenergic non-cholinergic innervation. This was largely prevented or corrected (4 weeks of treatment following 4 weeks of untreated diabetes) by 3-AB. Diabetes also markedly attenuated the maintenance of relaxation responses to prolonged stimulation, and ...Continue Reading

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Citations

Apr 11, 2009·International Journal of Molecular Medicine·Igor VareniukIrina G Obrosova
Sep 3, 2010·The Journal of Sexual Medicine·Zhihua H WanFeng Guo
May 4, 2007·Experimental Neurology·Igor VareniukIrina G Obrosova
Feb 13, 2009·British Journal of Pharmacology·Csaba Szabo
Aug 21, 2010·The American Journal of Pathology·Irina G ObrosovaRobert E Schmidt
Jul 23, 2013·European Journal of Pharmacology·P Sytze Van DamNorman E Cameron
Dec 2, 2017·British Journal of Pharmacology·Rachel M McQuadeKulmira Nurgali

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