Biomaterial Database

Sulphonylurea-sensitive channels and NO-cGMP pathway modulate the heart rate response to vagal nerve stimulation in vitro. 2000

S C Almond, and D J Paterson

University Laboratory of Physiology, Parks Road, Oxford, OX1 3PT, UK.

Sulphonylurea-sensitive K(+)channels (K(ATP)) have been implicated in the release of acetylcholine (ACh) from the vagus nerve in the heart. Our aim was to establish the functional significance of this and to test whether this modulation could interact with stimulation of the NO-cGMP pathway that facilitates the decrease in heart rate (HR) in response to vagal nerve stimulation (VNS). We studied the effect of activation (diazoxide, 100 microM) and inhibition (glibenclamide 30 microM or tolbutamide 5 microM) of K(ATP)channels, and activation of the NO-cGMP pathway with the NO donor, sodium nitroprusside (SNP, 20 microM) or the cGMP analogue, 8-Br-cGMP (0.5 m M) on the HR response to VNS in the isolated guinea pig (Cavia porcellus) double atrial/right vagus preparation (n=40). Tolbutamide increased the bradycardia in response to vagal stimulation at 3 and 5 Hz (P<0.05); effects that were reversed by diazoxide. Glibenclamide also significantly increased the HR response to VNS at 1 and 3 Hz (P<0.05). Diazoxide alone significantly attenuated the HR response to VNS at 5 Hz (P<0.05). Neither glibenclamide nor diazoxide affected the HR response to carbamylcholine (CCh, 50-200 n M). In the presence of a maximal dose of tolbutamide, SNP or 8-Br-cGMP further increased the HR response to VNS at 5 Hz (P<0.05). These results are consistent with the hypothesis that inhibition of sulphonylurea-sensitive channels can increase the HR response to VNS by a pre-synaptic mechanism, and that this modulation may be independent of activation of the NO-cGMP pathway.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009124	Muscle Proteins	The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.	Muscle Protein,Protein, Muscle,Proteins, Muscle
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
D009599	Nitroprusside	A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.	Nitroferricyanide,Sodium Nitroprusside,Cyanonitrosylferrate,Ketostix,Naniprus,Nipride,Nipruton,Nitriate,Nitropress,Nitroprussiat Fides,Nitroprusside, Disodium Salt,Nitroprusside, Disodium Salt, Dihydrate,Disodium Salt Nitroprusside,Nitroprusside, Sodium
D011188	Potassium	An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D003981	Diazoxide	A benzothiadiazine derivative that is a peripheral vasodilator used for hypertensive emergencies. It lacks diuretic effect, apparently because it lacks a sulfonamide group.	Hyperstat,Proglycem
D004558	Electric Stimulation	Use of electric potential or currents to elicit biological responses.	Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical
D005905	Glyburide	An antidiabetic sulfonylurea derivative with actions like those of chlorpropamide	Glibenclamide,Daonil,Diabeta,Euglucon 5,Euglucon N,Glybenclamide,HB-419,HB-420,Maninil,Micronase,Neogluconin,HB 419,HB 420,HB419,HB420
D006152	Cyclic GMP	Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)	Guanosine Cyclic 3',5'-Monophosphate,Guanosine Cyclic 3,5 Monophosphate,Guanosine Cyclic Monophosphate,Guanosine Cyclic-3',5'-Monophosphate,3',5'-Monophosphate, Guanosine Cyclic,Cyclic 3',5'-Monophosphate, Guanosine,Cyclic Monophosphate, Guanosine,Cyclic-3',5'-Monophosphate, Guanosine,GMP, Cyclic,Guanosine Cyclic 3',5' Monophosphate,Monophosphate, Guanosine Cyclic
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea