Biomaterial Database

Nitric oxide-induced vasodilation of organic nitrate-tolerant rabbit aorta. 1988

C J Slack, and B E McLaughlin, and K Nakatsu, and G S Marks, and J F Brien

Department of Pharmacology and Toxicology, Faculty of Medicine, Queen's University, Kingston, Ont., Canada.

It is postulated that the organic nitrate vasodilator agents, including glyceryl trinitrate (GTN) and isosorbide dinitrate (ISDN), are prodrugs, such that biotransformation to the active inorganic metabolite, nitric oxide (NO), occurs prior to the onset of vasodilation. Furthermore, it is proposed that organic nitrate tolerance in vascular tissue involves decreased formation of NO. To test this latter hypothesis, we examined vasodilation induced by NO, GTN, and ISDN in non-tolerant, GTN-tolerant, and ISDN-tolerant rabbit aortic rings (RARs). Isolated RARs were contracted submaximally with phenylephrine; the time of onset of relaxation and percent relaxation of tissue were determined in response to NO (0.3 microM), GTN (0.03 microM), and ISDN (0.12 microM) before and after a 1-h treatment with 500 microM GTN, 500 microM ISDN, or buffer only. The data demonstrated that the response to NO was not changed in GTN-tolerant and ISDN-tolerant tissues, in which there was virtually no GTN-induced or ISDN-induced relaxation. These results are consistent with the postulate that organic nitrate vasodilator drugs must undergo biotransformation to NO before vasodilation can occur and that the mechanism of organic nitrate tolerance involves decreased formation of NO.

UI	MeSH Term	Description	Entries
D007548	Isosorbide Dinitrate	A vasodilator used in the treatment of ANGINA PECTORIS. Its actions are similar to NITROGLYCERIN but with a slower onset of action.	Cardonit 40,Dilatrate,Iso-Bid,Isodinit,Isoket,Isoket Retard-120,Isomak R,Isordil,Isotrate,Nitrosorbide,Sorbitrate,Sorbonit,Dinitrate, Isosorbide,Iso Bid,IsoBid,Isoket Retard 120,Isoket Retard120
D008297	Male		Males
D009131	Muscle, Smooth, Vascular	The nonstriated involuntary muscle tissue of blood vessels.	Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D009569	Nitric Oxide	A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.	Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D011817	Rabbits	A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes.	Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D005996	Nitroglycerin	A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.	Glyceryl Trinitrate,Anginine,Dynamite,Gilustenon,Nitrangin,Nitro-Bid,Nitro-Dur,Nitrocard,Nitroderm,Nitroderm TTS,Nitroglyn,Nitrol,Nitrolan,Nitrong,Nitrospan,Nitrostat,Perlinganit,Susadrin,Sustac,Sustak,Sustonit,Transderm Nitro,Tridil,Trinitrin,Trinitrolong,Nitro Bid,Nitro Dur,NitroBid,NitroDur,Trinitrate, Glyceryl
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001013	Aorta, Thoracic	The portion of the descending aorta proceeding from the arch of the aorta and extending to the DIAPHRAGM, eventually connecting to the ABDOMINAL AORTA.	Aorta, Ascending,Aorta, Descending,Aortic Arch,Aortic Root,Arch of the Aorta,Descending Aorta,Sinotubular Junction,Ascending Aorta,Thoracic Aorta,Aortic Roots,Arch, Aortic,Ascending Aortas,Junction, Sinotubular,Root, Aortic,Sinotubular Junctions
D014664	Vasodilation	The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.	Vasodilatation,Vasorelaxation,Vascular Endothelium-Dependent Relaxation,Endothelium-Dependent Relaxation, Vascular,Relaxation, Vascular Endothelium-Dependent,Vascular Endothelium Dependent Relaxation
D066298	In Vitro Techniques	Methods to study reactions or processes taking place in an artificial environment outside the living organism.	In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In