[The effects of verapamil on the postischemic changes in the coronary microcirculation: the role of nitric oxide].
BACKGROUND
The aim of this study was to evaluate, in the model of isolated working rat heart, the effects of verapamil on postischemic changes in cardiac mechanical function and microvascular coronary permeability, and the possible role of nitric oxide.


METHODS
We used 72 male Wistar rats, weighing 250-300 g, divided into six groups: Group A, hearts perfused with modified Krebs-Henseleit solution (KH); Group B, hearts perfused with KH + verapamil 0.25 microM; Group C, hearts perfused with KH + verapamil 0.5 microM; Group D, hearts perfused with KH + verapamil 1 microM; Group E, hearts perfused with KH + NG-nitro-L-arginine methyl ester (L-NAME) 30 microM; Group F, hearts perfused with KH + verapamil 0.25 microM + L-NAME 30 microM. Hemodynamic parameters, necrosis enzyme release and fluoroscein isothiocyanate-albumin extravasation were evaluated.


RESULTS
We observed a clear preservation of cardiac mechanical function and microvascular function in Group B (low dose verapamil) compared to groups A (control), C and D (high dose verapamil); the inhibition of nitric oxide-synthase in the presence of verapamil, obtained in Group F, elicited a loss of myocardial protective effects of verapamil.


CONCLUSIONS
Our data suggest that low dose verapamil is effective on postischemic damage reduction and most probably nitric oxide plays a determinant role in this effect.
Di Napoli
P
P
Dipartimento di Scienze Cliniche e di Bioimmagini, Università degli Studi G D'Annunzio, Chieti.
Ranalli
G
G
Di Crecchio
A
A
Taccardi
A A
AA
Ausiello
A
A
Di Muzio
M
M
Barsotti
A
A
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D009569:Nitric Oxide; D014700:Verapamil; D019001:Nitric Oxide Synthase