The effect of substituted sydnonimines on coronary smooth muscle relaxation and cyclic guanosine monophosphate levels.

Abstract:

:In vitro experiments on precontracted canine coronary arteries were performed to study the direct relaxant effects of molsidomine (MOLS) and its active metabolite, SIN-1, and to determine if there is a relationship between effect and cGMP level elevations. The effects of MOLS and SIN-1 were compared with those of a classic vasodilator, nitroglycerin (NTG). At equimolar doses (10(-6)M) SIN-1 exerted greater relaxant effect than NTG (80 +/- 2% and 60 +/- 5%, respectively) in spite of the fact that it produced less of an increase in cyclic guanosine monophosphate (cGMP) levels. cGMP levels fell rapidly after they peaked, but relaxation was maintained. cGMP elevation preceded the induction of relaxation by NTG but not that induced by SIN-1. Relaxation occurred faster after NTG than after SIN-1. Since SIN-1 has a greater relaxant effect than NTG in spite of the fact that SIN-1 induces less of an increase in cGMP levels and the fact that the peak elevation does not precede the onset of relaxation, the causal nexus between GMP level elevation and relaxation effect after sydnonimines should be challenged.

journal_name

Circulation

journal_title

Circulation

authors

Rinaldi G,Cingolani H

doi

10.1161/01.cir.68.6.1315

subject

Has Abstract

pub_date

1983-12-01 00:00:00

pages

1315-20

issue

6

eissn

0009-7322

issn

1524-4539

journal_volume

68

pub_type

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