Intracellular vascular muscle Ca2+ modulation in genetic hypertension.
Distribution of intracellular free calcium concentration (Ca2+) was compared in spontaneously hypertensive rat (SHR) and Wistar-Kyoto (WKY) rat isolated vascular muscle cells at rest and during stimulation by K+ with Ca2+ agonist or antagonist. Ca2+ activity was quantitated at each point within vascular muscle cells loaded with fura-2 at fluorescence excitation wavelengths of 340, 360, and 380 nm, and fluorescence emission at 510 nm (all filters were +/- 5 nm) quantitated by a digital photon-counting camera. Measurements of fluorescence intensity ratio in central and subsarcolemmal areas showed that calcium release, in response to 30 or 100 mM K+ with Ca2+ agonist or during spontaneous contractions, was principally from sarcoplasmic reticulum. Addition of the Ca2+ agonist Sdz 202-791, S (+) stereoisomer (SdzS), caused a dose-dependent increase of Ca2+ in both SHR and WKY rats. Intracellular calcium release sites were defined by "hot spots" of high fluorescence intensity ratio in both central and peripheral regions of the sarcoplasm. The size and intensity of hot spots increased, and there was an initial transient activation of subsarcolemmal calcium pools in response to high K+ with 1 microM Ca2+ agonist. In contrast, treatment of the cells with the R (-) stereoisomer of Sdz 202-791 (SdzR), a Ca2+ antagonist, prevented the increase in Ca2+ and the increase in hot spot size by either K+ alone or with agonist. Antagonist decreased central core Ca2+ release and fragmented the subsarcolemmal hot spots.(ABSTRACT TRUNCATED AT 250 WORDS)
Chiles Research Institute, Providence Medical Center, Portland, Oregon 97213.
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Erne
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Hermsmeyer
D000818:Animals; D002118:Calcium / Q000032:analysis*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000032:analysis*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D002121:Calcium Channel Blockers; D011188:Potassium; D002118:Calcium