Previous reports have suggested that angiotensin converting enzyme (ACE) inhibitors are able to modulate intercellular resistance through an ACE-independent action. Therefore, the aim of our study was to determine whether the ACE inhibitor lisinopril would modulate intercellular resistance of guinea pig ventricular myocytes. Junctional resistance was measured using the double patch-clamp technique in eight cell pairs at baseline and during superfusion with 10(-4) M lisinopril. In these cell pairs, mean junctional resistance (+/-SEM) measured at baseline (14.5 +/- 3.8 M omega) was unchanged (15.0 +/- 3.6 M omega; p > 0.05) during lisinopril even after a 25-min exposure to the drug (n = 3). As well, a 20-min exposure to 10(-6) M lisinopril from the intracellular milieu did not modify the junctional resistance. In conclusion, this study demonstrates that modulation of junctional resistance independent of drug-related ACE inhibition is not observed with lisinopril.