Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. After a period of myocardial ischaemia, reperfusion of the myocardium can elicit cardiac arrhythmias. Susceptibility to these arrhythmias declines with time, such that a preceding period of more than approximately 40 min ischaemia is associated with few reperfusion-induced arrhythmias. We have tested the hypothesis that this decline in susceptibility occurs, in part, because of protection by endogenous guanosine 3':5'-cyclic monophosphate (cyclic GMP). 2. Rat isolated hearts were subjected to 60 min left regional ischaemia followed by reperfusion (n = 10 per group). Methylene blue (20 microM), a soluble guanylate cyclase inhibitor, raised the incidence of reperfusion-induced ventricular fibrillation (VF) from 10% in control hearts to 80% (P < 0.05). This effect of methylene blue was abolished by co-perfusion with zaprinast (100 microM), a phosphodiesterase inhibitor which, in the rat heart, is cyclic GMP-specific (specific for the type-V phosphodiesterase isozyme). 3. Methylene blue reduced cyclic GMP levels in the ischaemic, non-ischaemic and reperfused myocardium (P < 0.05) to 50 +/- 10, 52 +/- 12 and 70 +/- 7 fmol mg-1 tissue wet weight, respectively from control values of 143 +/- 38, 147 +/- 43 and 156 +/- 15 fmol mg-1. Co-perfusion with zaprinast prevented this effect, and cyclic GMP levels were actually elevated (P < 0.05) to 366 +/- 102, 396 +/- 130 and 293 +/- 22 fmol mg-1 in ischaemic, non-ischaemic and reperfused myocardium, respectively. Zaprinast by itself also elevated cyclic GMP content. Cyclic AMP levels were not affected by zaprinast or methylene blue. 4. In conclusion, when endogenous cardiac cyclic GMP synthesis is reduced, susceptibility to reperfusion-induced VF after sustained ischaemia is substantially increased. The effect is prevented by inhibiting cyclic GMP degradation. Therefore cyclic GMP appears to be an endogenous intracellular cardioprotectant, and its actions may account for the low susceptibility to VF normally encountered in hearts reperfused after sustained ischaemia.
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PMID:An endogenous protectant effect of cardiac cyclic GMP against reperfusion-induced ventricular fibrillation in the rat heart. 868 Jul 26

Isolated rat hearts were perfused for 10 min with oxygenated buffer and equilibrated with carbon monoxide (CO) of 0.001% and 0.01% before the induction of 30 min global ischemia followed by 120 min of reperfusion. These concentrations of CO significantly improved the post-ischemic recovery of coronary flow (CF), aortic flow (AF), and left ventricular developed pressure (LVDP). The improvement in recovery reflected in the reduction of infarct size and the incidence of reperfusion-induced ventricular fibrillation (VF). Thus, hearts subjected to 0.001% and 0.01% of CO exposure via the perfusion buffer, infarct size was reduced from the CO-free control value of 39% +/- 5% to 21% +/- 3% (*p<0.05) and 18% +/- 4% (*p<0.05), respectively. In the presence of 0.001% and 0.01% CO, the incidence of VF was also reduced from its control value of 92% to 17% (*p<0.05) and 17% (*p<0.05), respectively. Increasing the CO exposure to 0.1% in the buffer, all hearts showed VF combined with ventricular tachycardia or bradycardia and various rhythm disturbances indicating the direct toxic effects of CO on the myocardium. The results show that cardioprotective concentrations (0.01% and 0.001%) of exogenous CO related to an increase in cGMP levels and guanylate cyclase activities.
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PMID:The role of exogenous carbon monoxide in the recovery of post-ischemic cardiac function in buffer perfused isolated rat hearts. 1630 67