It was seen that low concentrations of a hydrophilic nitric oxide donor (NOD), 4-[(dimethylamino)mehyil]furoxan-3-carboxyamide, reduce myocardial reperfusion injury only if combined in a hybrid molecule (HYB) with a lipohilic antioxidant (AOX) 2,2,5,7,8-pentamethylchroman-6-ol. It was argued that HYB allows hydrophilic NOD to enter the cell. We tested whether liposoluble-NOD needs to be combined with AOX to be protective. Isolated rat hearts underwent 30-min ischemia and 120-min reperfusion. To induce postconditioning, 1 mM solutions of one of the following liposoluble compounds were given during the first 20-min of reperfusion: 4-methoxy-3-phenylfuroxan with weak NO releasing potency (w-NOD); 4-methoxy-3-phenysulfonillfuroxan with strong NO releasing potency (s-NOD); hybrid compound of w-NOD and a per se ineffective concentration of AOX lead (w-HYB); hybrid compound of s-NOD and the same AOX (w-HYB); mixtures of w-NOD plus AOX (w-MIX) and s-NOD plus AOX (s-Mix). A significant reduction of infarct size with improved recovery of contractility was seen only with w-HYB. We suggest that w-NOD needs the synergy with a per se ineffective AOX concentration to protect. The synergy is possible if the two leads enter the cell simultaneously as a hybrid molecule, but not as a mixture. We presume that s-HYB was ineffective because an excessive intracellular release of NO produces a too large amount of reactive species, as previously suggested with high concentrations of hydrophilic-NOD.

CONTRIBUTION OF ANTIOXIDANT COMPOUND TO THE PROTECTIVE EFFECT OF NITRIC OXIDE DONORS

FOLINO, Anna;RASTALDO, Raffaella;CAPPELLO, SANDRA;PAGLIARO, Pasquale;LOSANO, Giovanni
2011-01-01

Abstract

It was seen that low concentrations of a hydrophilic nitric oxide donor (NOD), 4-[(dimethylamino)mehyil]furoxan-3-carboxyamide, reduce myocardial reperfusion injury only if combined in a hybrid molecule (HYB) with a lipohilic antioxidant (AOX) 2,2,5,7,8-pentamethylchroman-6-ol. It was argued that HYB allows hydrophilic NOD to enter the cell. We tested whether liposoluble-NOD needs to be combined with AOX to be protective. Isolated rat hearts underwent 30-min ischemia and 120-min reperfusion. To induce postconditioning, 1 mM solutions of one of the following liposoluble compounds were given during the first 20-min of reperfusion: 4-methoxy-3-phenylfuroxan with weak NO releasing potency (w-NOD); 4-methoxy-3-phenysulfonillfuroxan with strong NO releasing potency (s-NOD); hybrid compound of w-NOD and a per se ineffective concentration of AOX lead (w-HYB); hybrid compound of s-NOD and the same AOX (w-HYB); mixtures of w-NOD plus AOX (w-MIX) and s-NOD plus AOX (s-Mix). A significant reduction of infarct size with improved recovery of contractility was seen only with w-HYB. We suggest that w-NOD needs the synergy with a per se ineffective AOX concentration to protect. The synergy is possible if the two leads enter the cell simultaneously as a hybrid molecule, but not as a mixture. We presume that s-HYB was ineffective because an excessive intracellular release of NO produces a too large amount of reactive species, as previously suggested with high concentrations of hydrophilic-NOD.
2011
62 National Congress of the Italian Physiological Society
Sorrento
25-27 settembre 2011
203
235
235
FOLINO A; RASTALDO R; CAPPELLO S; PAGLIARO P; LOSANO G.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/97365
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact