Abstract

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.

LLU Discipline

Physiology

Department

Physiology

School

Graduate School

First Advisor

Ramon R. Gonzalez, Jr.

Second Advisor

Ian M. Fraser

Third Advisor

Raymond G. Hall, Jr.

Fourth Advisor

George Maeda

Fifth Advisor

Grenith J. Zimmerman

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

1994

Date (Title Page)

12-1994

Language

English

Library of Congress/MESH Subject Headings

Muscle, Smooth, Vascular; Endothelium; Pentobarbital

Type

Dissertation

Page Count

viii; 94

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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Physiology Commons

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