Vol. 292, Issue 1, 196-200, January 2000

Effects of Captopril Treatment of Renovascular Hypertension on -Adrenergic Modulation of L-Type Ca²⁺ Current¹

Xiaoping Xu, Seth J. Rials², Ying Wu, Tengxian Liu, Roger A. Marinchak and Peter R. Kowey

Cardiovascular Division, The Lankenau Hospital and Medical Research Center, Wynnewood, Pennsylvania

-Adrenergic stimulation of cardiac L-type Ca²⁺ channels is severely impaired in hypertrophied and failing hearts of both experimental animals and humans. The aim of this study was to test the hypothesis that chronic treatment of renovascular hypertension with captopril restores normal -adrenergic responsiveness of L-type Ca²⁺ channels in cardiac myocytes. Left ventricular hypertrophy was induced in rabbits by unilateral renal artery banding and contralateral nephrectomy. Beginning at 3 months after banding, hypertensive rabbits were treated with captopril for 3 months. The responsiveness of L-type Ca²⁺ current (I_Ca,L) to (±)-isoproterenol was investigated with the whole-cell patch-clamp technique. (±)-Isoproterenol (1 µM) induced an increase of I_Ca,L at 0 mV of 126 ± 20% (n = 13) in control myocytes 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. Forskolin (10 µM) induced a similar percentage of increase of I_Ca,L in control and hypertrophied myocytes, 109 ± 13% (n = 12) versus 120 ± 14% (n = 11) at 0 mV. The responsiveness of I_Ca,L to (±)-isoproterenol remained depressed in untreated hypertensive rabbits. (±)-Isoproterenol (1 µM) increased I_Ca,L at 0 mV by 64 ± 8% (n = 14) in myocytes isolated from rabbits 6 months after banding versus 111 ± 15% (n = 16) in age-matched controls. In captopril-treated rabbits, 1 µM (±)-isoproterenol increased I_Ca,L by 110 ± 11% (n = 17). We conclude that the maximal response of I_Ca,L to (±)-isoproterenol was severely depressed in hypertrophied myocytes. Chronic treatment of renovascular hypertension with captopril can restore normal responsiveness of I_Ca,L to (±)-isoproterenol in cardiac myocytes.