Effects of captopril treatment of renovascular hypertension on beta-adrenergic modulation of L-type Ca(2+) current.
beta-Adrenergic stimulation of cardiac L-type Ca(2+) 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 beta-adrenergic responsiveness of L-type Ca(2+) 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 Ca(2+) current (I(Ca,L)) to (+/-)-isoproterenol was investigated with the whole-cell patch-clamp technique. (+/-)-Isoproterenol (1 microM) 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 microM) 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 microM) 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 microM (+/-)-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.
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Cardiovascular Division, The Lankenau Hospital and Medical Research Center, Wynnewood, PA, USA. xxujwang@aol.com
Rials
S J
SJ
Wu
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Liu
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Marinchak
R A
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Kowey
P R
PR
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology* / Q000627:therapeutic use; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006321:Heart / Q000187:drug effects*; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D009392:Nephrectomy; D018408:Patch-Clamp Techniques; D011817:Rabbits; D011897:Random Allocation; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D012077:Renal Artery / Q000601:surgery; D013997:Time Factors
D015220:Calcium Channels; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D002216:Captopril; D007545:Isoproterenol