Mechanism of Action of Pentobarbital Induced Attenuation of Vascular Smooth Muscle Contraction

<p>Pentobarbital (PB) vasodilates dog mesenteric and cerebral arteries precontracted with KC1, PGF_2α, 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 A_7r5 (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.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Physiology

Year

1994

Author dc:creator

• Samardzija, Michael R.

Contributors dc:contributor

• Ramon R. Gonzalez, Jr.
• Ian M. Fraser
• Raymond G. Hall, Jr.
• George Maeda
• Grenith J. Zimmerman

• Physiology
• Muscle, Smooth, Vascular; Endothelium; Pentobarbital

Statement dc: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.

Language dc:language

English

Repository record dc:identifier

https://scholarsrepository.llu.edu/etd/990

OAI identifier oai:identifier

oai:scholarsrepository.llu.edu:etd-2054