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Cyclic GMP-independent relaxation and hyperpolarization with acetylcholine in guinea-pig coronary artery.

Abstract：

:1. The effects of acetylcholine (ACh) on membrane potential, relaxation and cyclic GMP levels were compared to the NO donor L-nitrosocysteine (Cys-NO) in segments of guinea-pig coronary artery. 2. ACh and Cys-NO produced concentration-dependent relaxations of muscles contracted with the H1 receptor agonist, 2-(2-aminoethyl)pyridine (AEP, 0.35 mM). The relaxation to ACh was unchanged in the presence of NG-monomethyl-L-arginine (L-NMMA; 350 microM) or indomethacin (3 microM). 3. Oxyhaemoglobin (HbO; 20 microM) alone or in combination with L-NMMA increased the EC50 for ACh-induced relaxation whereas relaxation with Cys-NO was almost completely abolished with HbO. 4. Scorpion venom (SV; 8.7 micrograms ml-1) increased the EC50 for relaxation with ACh but not Cys-NO. Combined L-NMMA, HbO and SV produced nearly complete abolition of ACh-induced relaxations. 5. Basal cyclic GMP levels (i.e., 20 pmol mg-1 protein) were significantly increased following addition of either ACh (190 pmol mg-1 protein) or Cys-NO (240 pmol mg-1 protein). L-NMMA significantly reduced the rise of cyclic GMP with ACh but not Cys-NO. In contrast, SV did not significantly reduce the rise in cyclic GMP produced with ACh. In the combined presence of L-NMMA and HbO neither ACh nor Cys-NO produced a significant increase in cyclic GMP levels. 6. ACh gave rise to significantly greater membrane hyperpolarization than Cys-NO both in the presence and absence of AEP. Combined L-NMMA and HbO did not reduce the amplitude of hyperpolarization with ACh. 7. These data indicate that some but not all of the actions of ACh in the coronary artery can be mimicked by the NO donor, Cys-NO, suggesting that ACh releases NO as well as a second hyperpolarizing factor (i.e., EDHF). Release of NO results in a large increase in tissue cyclic GMP levels and minimal change in membrane potential whereas release of EDHF results in a large membrane hyperpolarization which is independent of changes in tissue cyclic GMP levels. Both of these pathways appear to contribute to relaxation throughout the entire ACh concentration-relaxation relationship.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Eckman DM,Weinert JS,Buxton IL,Keef KD

doi

10.1111/j.1476-5381.1994.tb14851.x

subject

Has Abstract

pub_date

1994-04-01 00:00:00

pages

1053-60

issue

eissn

0007-1188

issn

1476-5381

journal_volume

111

pub_type

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Cyclic GMP-independent relaxation and hyperpolarization with acetylcholine in guinea-pig coronary artery.