Decreased dihydropyridine receptor number in hypertensive rat vascular muscle cells.
To further investigate the altered function of Ca2+ channels in vascular muscle cells in hypertension, a novel fluorescently labeled dihydropyridine was used with ultrahigh-sensitivity photometry to study dihydropyridine binding sites on the surface membrane of living vascular muscle cells from stroke-prone spontaneously hypertensive rats and their normotensive controls. Fluorescent nitrobenzoxadiazol-6-dihydropyridine in concentrations of 1 to 100 nmol/L bound specifically to vascular muscle cells' Ca2+ channels, and was displaced by the unlabeled dihydropyridine analogue or nisoldipine (10 mumol/L). Stroke-prone spontaneously hypertensive rat vascular muscle cells showed significantly decreased binding of nitrobenzoxadiazol-6-dihydropyridine compared with normotensive National Institutes of Health rats. Decreased binding of dihydropyridine by vascular muscle cells from stroke-prone spontaneously hypertensive rats (cells that in other studies show increased Ca2+ channel function) indicates a change in channel regulation that is possibly due to a deficiency in the inactivation mechanism, consistent with our earlier electrophysiological studies reporting deficiencies in Ca(2+)-dependent inactivation in genetic hypertension. These data demonstrate decreased numbers of localized sites of dihydropyridine binding on the sarcolemma of living vascular muscle cells, and support the hypothesis that Ca2+ channel alterations may significantly contribute to the molecular etiology of genetic hypertension.
Hermsmeyer
K
K
Oregon Regional Primate Research Center, Beaverton 97006, USA.
White
A C
AC
Triggle
D J
DJ
D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D020746:Calcium Channels, L-Type; D002478:Cells, Cultured; D002561:Cerebrovascular Disorders / Q000235:genetics; D004198:Disease Susceptibility; D006973:Hypertension / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D009568:Nitrendipine / Q000031:analogs & derivatives; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics; D012016:Reference Values
C093223:5-methyl 3-(6-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexyl 1,4-dihydro-2,6-dimethyl-4-(2-trifluoromethyl)phenyl-3,5-pyridinedicarboxylate; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D009124:Muscle Proteins; D009568:Nitrendipine; D009327:4-Chloro-7-nitrobenzofurazan