Role of cyclic guanosine monophosphate in late preconditioning in conscious rabbits

Eitaro Kodani ¹, Yu-Ting Xuan , Hitoshi Takano

⁰Experimental Research Laboratory, Division of Cardiology, University of Louisville and the Jewish Heart and Lung Institute, Louisville, Ky 40292, USA.

Circulation +

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June 26, 2002

View abstract on PubMed

Summary

Nitric oxide (NO) triggers late ischemic preconditioning (PC) independently of soluble guanylate cyclase (sGC) activation. However, sGC activation is essential for NO to mediate PC protection 24 hours later.

Area Of Science

Cardiovascular Physiology
Ischemic Preconditioning Research
Nitric Oxide Signaling

Background

Nitric oxide (NO) is implicated in both triggering and mediating late ischemic preconditioning (PC).
The specific role of soluble guanylate cyclase (sGC) in NO-mediated late PC remains unclear.

Purpose Of The Study

To investigate the role of sGC in late PC using a selective sGC inhibitor (ODQ) in conscious rabbits.

Main Methods

172 conscious rabbits underwent coronary occlusion/reperfusion cycles.
Myocardial cyclic guanosine monophosphate (cGMP) levels were measured.
ODQ was administered before PC induction (day 1) or before testing protection (day 2).

Main Results

Preconditioning increased myocardial cGMP levels 24 hours later.
ODQ administration on day 1 did not inhibit late PC development.
ODQ administration on day 2 abolished the protective effects of late PC against stunning and infarction.

Conclusions

sGC activation is not required for ischemia to trigger late PC.
sGC-dependent cGMP synthesis is essential for the manifestation of late PC protection 24 hours post-induction.
NO utilizes distinct mechanisms: cGMP-independent triggering and cGMP-dependent mediation of late PC.

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