Calcium current in smooth muscle cells from normotensive and genetically hypertensive rats.
Genetic hypertension results from numerous phenotypic expressions. We hypothesized that increased calcium current in vascular smooth muscle of genetically hypertensive animals is partly responsible for observed increases in agonist sensitivity, contractility, and calcium influx. Using adult, spontaneously hypertensive stroke-prone rats (SHRSP) and normotensive Wistar-Kyoto (WKY) controls from an inbred colony, we characterized calcium current in smooth muscle cells isolated from cerebral arteries. Calcium current in WKY cells reached a maximum of -27.7 +/- 2.7 pA (n = 32) at +20 mV. Peak inward current at +20 mV in SHRSP cells had a mean amplitude of -44.4 +/- 3.0 pA (n = 72, P < .05). SHRSP cells exhibited a higher calcium current density. Maximal inward current normalized to cell capacitance yielded mean values of 2.07 +/- 0.11 pA/pF for WKY (n = 32) and 2.80 +/- 0.12 pA/pF (n = 79) for SHRSP (P < .05) cells. Transient-type Ca2+ channel current had the same magnitude and current-voltage relation in both cell types, giving an L-type/T-type ratio of 3.85 for WKY and 6.25 for SHRSP cells. The voltage-dependent inactivation curve for SHRSP calcium current was shifted to the right only over the range of -50 to -30 mV, but the half-maximal inactivation voltages and Boltzmann coefficients were not significantly different between cell types. Increased calcium inward current in this model of genetic hypertension could account in part for altered calcium homeostasis and increased vascular reactivity, contributing to hypertension and vasospasm.
Wilde
D W
DW
Department of Anesthesiology, University of Michigan Medical School, Ann Arbor.
Furspan
P B
PB
Szocik
J F
JF
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002469:Cell Separation; D002561:Cerebrovascular Disorders / Q000235:genetics; D004553:Electric Conductivity; D020022:Genetic Predisposition to Disease; D006973:Hypertension / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics / Q000502:physiology; D011921:Rats, Inbred WKY; D013997:Time Factors
D015220:Calcium Channels; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester