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.
","abstract_html":"<p>Pentobarbital (PB) vasodilates dog mesenteric and cerebral arteries precontracted with KC1, PGF<sub>2α</sub>, caffeine or norepinephrine. It is postulated that PB causes this dilation by reducing Ca<sup>2+</sup> influx as a non-specific Ca<sup>2+</sup> channel blocker, or decreasing intracellular Ca<sup>2+</sup> release. We examined PB effects on intracellular Ca<sup>2+</sup> release (ICR) and extracellular Ca<sup>2+</sup> 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% CO<sub>2</sub>. 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 Ca<sup>2+</sup> 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<sub>7r5</sub> (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>","abstract_has_math":false,"creators":["Samardzija, Michael R."],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Physiology","degree_department":null,"school":null,"contributors":["Ramon R. Gonzalez, Jr.","Ian M. Fraser","Raymond G. Hall, Jr.","George Maeda","Grenith J. Zimmerman"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":1994,"date_issued":"1994-12-01T08:00:00Z","date_published":"1994-12-01T08:00:00Z","updated_at":"2026-07-24T02:53:37Z","subjects":["Physiology","Muscle, Smooth, Vascular; Endothelium; Pentobarbital"],"languages":["English"],"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."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://scholarsrepository.llu.edu/etd/990","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Ramon R. Gonzalez, Jr.","Ian M. Fraser","Raymond G. Hall, Jr.","George Maeda","Grenith J. 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The author retains all other copyrights."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarsrepository.llu.edu/etd/990"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.
"]},{"key":"dc:title","label":"Title","values":["Mechanism of Action of Pentobarbital Induced Attenuation of Vascular Smooth Muscle Contraction"]}]}],"canonical_facts":{"dc:contributor":["Ramon R. Gonzalez, Jr.","Ian M. Fraser","Raymond G. Hall, Jr.","George Maeda","Grenith J. Zimmerman"],"dc:creator":["Samardzija, Michael R."],"dc:description.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.
"],"dc:identifier":["https://scholarsrepository.llu.edu/etd/990"],"dc:language":["English"],"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."],"dc:subject":["Physiology","Muscle, Smooth, Vascular; Endothelium; Pentobarbital"],"dc:title":["Mechanism of Action of Pentobarbital Induced Attenuation of Vascular Smooth Muscle Contraction"],"thesis:degree_discipline":["Physiology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T02:53:37Z"}