Mechanism of Action of Pentobarbital Induced Attenuation of Vascular Smooth Muscle Contraction
Pentobarbital (PB) vasodilates dog mesenteric and cerebral arteries precontracted with KC1, PGF2α, caffeine or norepinephrine. It is postulated that PB causes this dilation by reducing Ca2+ influx as a non-specific Ca2+ channel blocker, or decreasing intracellular Ca2+ release. We examined PB effects on intracellular Ca2+ release (ICR) and extracellular Ca2+ influx (ECI) by stimulating Sprague-Dawley rat tail artery rings with either 100 mM KC1, 50 uM phenylephrine (PE), or two different electrical field stimulation (EES) parameters: tetrodotoxin (TTX; 1 uM) sensitive, or perivascular nerve, (NEFS) stimulation (10 Hz, 0.3 ms, 50 V, 30 sec), and direct smooth muscle (MEFS) stimulation in the presence of TTX (10 Hz, 3 ms, 50 V, 30 sec). Rings, preloaded at 1 g, were immersed in an organ bath filled with Krebs solution at 37°C, and aerated with 95% 02:5% CO2. PB (1 mM) attenuated only the tonic component of contraction induced by PE and NEFS by 80%, but reduced KC1 and MEFS total contraction by 80%. PE and NEFS induces ICR from the sarcoplasmic reticulum and, with diacyl glycerol, opens receptor operated Ca2+ channels. KC1 and MEFS increases ECI. PB is also thought to increase fluidity of both artificial and nerve membranes. We examined ECI as a function of altered membrane fluidity in A7r5 (embryonic rat aortic) VSM cells. Fluidity was increased by treatment with docosahexaenoic acid (22:6), a polyunsaturated fatty acid (PUFA), to compare the effects of PB (30 uM, 20 min). PUFA and/or PB treatment had no effect on transient ECI in resting cells over a range of temperatures (32, 34.5, 37, 39.5, 41°C). However, both PUFA and/or PB treatment of cells depolarized with 55 mM KC1 in HEPES buffered (pH 7.4) physiologic saline solution decreased ECI by 25% over the same temperature range. PUFA/PB combination had an additive inhibitory effect (45% decrease). These data suggest that PB may increase membrane fluidity, and thus attenuate the tonic component of contraction in VSM, implying that PB interferes with ECI and not ICR.
Ramon R. Gonzalez, Jr.
Ian M. Fraser
Raymond G. Hall, Jr.
Grenith J. Zimmerman
Doctor of Philosophy (PhD)
Year Degree Awarded
Date (Title Page)
Library of Congress/MESH Subject Headings
Muscle, Smooth, Vascular; Endothelium; Pentobarbital
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Samardzija, Michael R., "Mechanism of Action of Pentobarbital Induced Attenuation of Vascular Smooth Muscle Contraction" (1994). Loma Linda University Electronic Theses, Dissertations & Projects. 990.
Loma Linda University Electronic Theses and Dissertations
Loma Linda University. Del E. Webb Memorial Library. University Archives