Abstract
β-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 β-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 (ICa,L) to (±)-isoproterenol was investigated with the whole-cell patch-clamp technique. (±)-Isoproterenol (1 μM) induced an increase of ICa,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 ICa,L in control and hypertrophied myocytes, 109 ± 13% (n = 12) versus 120 ± 14% (n = 11) at 0 mV. The responsiveness of ICa,L to (±)-isoproterenol remained depressed in untreated hypertensive rabbits. (±)-Isoproterenol (1 μM) increased ICa,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 ICa,L by 110 ± 11% (n = 17). We conclude that the maximal response of ICa,L to (±)-isoproterenol was severely depressed in hypertrophied myocytes. Chronic treatment of renovascular hypertension with captopril can restore normal responsiveness of ICa,Lto (±)-isoproterenol in cardiac myocytes.
Footnotes
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Send reprint requests to: Xiaoping Xu, Ph.D., Suite 558, Medical Office Building East, 100 Lancaster Ave., Wynnewood, PA 19096. E-mail: xxujwang{at}aol.com
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↵1 This work was supported in part by a grant from American Heart Association Southeastern Pennsylvania Affiliate (to X.X.).
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↵2 Current address: Diagnostic Cardiovascular Consultants, Inc., 300 East Town St., Suite 1400, Columbus, OH 43215.
- Abbreviations:
- ACE
- angiotensin-converting enzyme
- LVH
- left ventricular hypertrophy
- HW
- heart weight
- BW
- body weight
- HW/BW
- heart weight-to-body weight ratio
- Received June 29, 1999.
- Accepted August 31, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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