Effects of captopril treatment of renovascular hypertension on beta-adrenergic modulation of L-type Ca2+ current

beta-Adrenergic stimulation of cardiac L-type Ca2+ channels is severely imp aired in hypertrophied and failing hearts of both experimental animals and humans. The aim of this study was to test the hypothesis that chronic treat ment of renovascular hypertension with captopril restores normal beta-adren ergic responsiveness of L-type Ca2+ channels in cardiac myocytes. Left vent ricular hypertrophy was induced in rabbits by unilateral renal artery bandi ng and contralateral nephrectomy. Beginning at 3 months after banding, hype rtensive rabbits were treated with captopril for 3 months. The responsivene ss of L-type Ca2+ current (I-Ca,I-L)to (+/-)-isoproterenol was investigated with the whole-cell patch-clamp technique. (+/-)- Isoproterenol (1 mu M) i nduced an increase of I-Ca,I-L at 0 mV of 126 +/- 20% (n = 13) in control m yocytes versus 69 +/- 11% (n = 18) in hypertrophied myocytes from rabbits 3 months after banding. The half-maximal activation concentration of (+/-)- isoproterenol was similar between control and hypertrophied myocytes. Forsk olin (10 mu M) induced a similar percentage of increase of I-Ca,I-L in cont rol and hypertrophied myocytes, 109 +/- 13% (n = 12) versus 120 +/- 14% (n = 11) at 0 mV. The responsiveness of I-Ca,I-L to (+/-) isoproterenol remain ed depressed in untreated hypertensive rabbits. (+/-)- Isoproterenol (1 mu M) increased I-Ca,I-L at 0 mV by 64 +/- 8% (n = 14) in myocytes isolated fr om rabbits 6 months after banding versus 111 +/- 15% (n = 16) in age-matche d controls. In captopril-treated rabbits, 1 mM (6)- isoproterenol increased I-Ca,I-L by 110 +/- 11% (n = 17). We conclude that the maximal response of I-Ca,I-L to (+/-)-isoproterenol was severely depressed in hypertrophied my ocytes. Chronic treatment of renovascular hypertension with captopril can r estore normal responsiveness of I-Ca,I-L to (+/-)-isoproterenol in cardiac myocytes.