Effects of captopril on membrane current and contraction in single ventricular myocytes from guinea‐pig

Abstract

1Single guinea-pig ventricular myocytes were voltage-clamped and cell length was measured with a photodiode array. 2 Captopril (1 x 10-5M) reduced both peak early current and active shortening in response to a depolarizing clamp pulse along a similar time course. 3 From a holding potential of around -45 mV peak early inward current was reduced by 37 + 9% (P < 0.001) on exposure to captopril. The early current-voltage relationship was shifted outwards by captopril indicating a reduction in membrane conductance through the L-type calcium channel (ICa). 4 The amplitude of cell shortening in response to depolarizing voltage steps was reduced but the voltage-dependence of contraction after captopril was unchanged.5 A small negative shift of the potential at which Ica was half-activated was observed after captopril.There was no change in the voltage-dependence of the inactivation variable or in the time-dependence of repriming for ICa 6 The actions of captopril on ICa and developed shortening were dose-dependent and took place in the same proportion when ICa was increased by isoprenaline. 7 These results are discussed in relation to the effects of captopril on ICa and contraction and to its clinical usage.

Regulation of L-type inward calcium channel activity by captopril and angiotensin II via the phosphatidyl inositol 3-kinase pathway in cardiomyocytes from volume-overload hypertrophied rat hearts

“…Therefore, it may be argued that captopril’s negative effect on I Ca,L is not through the Ang II system or PI3-kinase signaling. In support of our data, earlier reports also showed that treatment with captopril decreased the I Ca,L level of normal ventricular myocytes (Bryant et al 1991), as well as reduced calcium influx without affecting the resting baseline Ca 2+ concentration of WKY rats (Wang et al 1996). …”

Effects of lisinopril on electromechanical properties and membrane currents in guinea‐pig cardiac preparations

“…Under these conditions a concentration of lisinopril (10 LM), which reduced the developed contractile force by almost 50%, had no effect on the amplitude or the voltage-dependent properties of the ICa,L. Therefore, and in contrast to what has been previously described with captopril (Bryant et al, 1991), the present experiments demonstrated that the negative inotropic effect of lisinopril cannot be explained through a decrease in Ca2" entry via L-type channels.…”

“…However, lisinopril had no effect on atrial rate and sinus node recovery time, which suggested that it does not exert a direct inhibition of the sinus node function. Captopril also produced a negative inotropic effect in guinea-pig isolated hearts (Walker et al, 1988) and this effect was attributed to an inhibition of ICaL (Bryant et al, 1991). However, in the present experiments the decrease in contractile force appeared at concentrations at which lisinopril had no effect on the duration of the cardiac action potentials.…”

“…Moreover, recent evidence confirmed that chronic angiotensin-converting enzyme inhibition may improve survival in experimental models (Pfeffer et al, 1985;Sweet et al, 1987) and in patients with asymptomatic (SOLVD, 1992) and severe heart failure of various aetiologies (Consensus, 1987;SOLVD, 1991;Pfeffer et al, 1992). Very recently, it has been found that captopril, a sulphydryl angiotensin-converting enzyme inhibitor, reduced contractile force in guinea-pig isolated hearts (Walker et al, 1988), an effect which in isolated ventricular cells has been attributed to an inhibition of Ca2+ entry through voltage-dependent L-type channels, ICa,L (Bryant et al, 1991). However, it is unknown whether this negative inotropic effect is related or not to the chemical structure (-SH group) of captopril.…”

Mechanism of the Action of Angiotensin-Converting Enzyme Inhibitors on Agonist-Induced Ca²⁺ Influx

“…Furthermore, it was demonstrated that these inhibitory effects of captopril and enalaprilat on Ca2+ influx in VSMC were paralleled by a decreased 268 Zhu/Tepel/Neusser/Zidek Angiotensin-Converting Enzyme Inhibitors and Cytosolic Calcium contractile response to Ang II [23], This study also showed that the attenuation of the Ang II response is due to an inhibition of transplasma membrane Ca2+ influx. Interestingly, similar effects of captopril have also been observed in ventricular myocytes, indicating that Ca2+ influx through L-type channels as well as contraction is inhibited by captopril [24], From these results several questions arose. First, is ago nist-induced Ca2+ influx inhibited similarly by different ACE inhibitors?…”