Linked Life Data

11430921

Source:http://linkedlifedata.com/resource/pubmed/id/11430921

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2001-6-29
pubmed:abstractText
Nitric oxide (NO) donors including organic nitrates dilate capacitance vessels. As inhibition of phosphodiesterase type 5 results in the accumulation of guanosine 3'5'-cyclic monophosphate (cGMP), specific phosphodiesterase type 5 inhibitors are expected to have a vasodilator property similar to that of NO donors. To test this hypothesis, we examined the effect of methyl2-(4-aminophenyl)-1,2-dihydro-1-oxo-7-(2-pyridinylmethoxy)-4-(3,4,5-trimethoxyphenyl)-3-isoquinoline carboxylate sulfate (T-1032), a novel specific phosphodiesterase type 5 inhibitor, on mean arterial pressure and mean circulatory filling pressure (an index of venodilation) compared with that of nitroglycerin and diltiazem in mecamylamine- and noradrenaline-treated anesthetized rats. Intravenous infusion of T-1032 (0.1, 1, 10 microg/kg/min) dose-dependently decreased mean arterial pressure (-3.8+/-0.3%, -9.1+/-0.8%, -16.8+/-1.5% at doses of 0.1, 1 and 10 microg/kg/min, respectively) and mean circulatory filling pressure (-6.1+/-0.9%, -12.5+/-0.7%, -18.6+/-3.0% at doses of 0.1, 1 and 10 microg/kg/min, respectively). The mean circulatory filling pressure-mean arterial pressure relationship revealed that T-1032 had a selective action on the mean circulatory filling pressure compared with diltiazem (10, 100 microg/kg/min) and a similar or more selective effect than nitroglycerin (0.3, 3 and 30 microg/kg/min). In the next study, we calculated venous compliance and unstressed volume from the mean circulatory filling pressure-volume relationship. Intravenous infusion of T-1032 (3 microg/kg/min) increased venous compliance (3.35+/-0.40 in T-1032 vs. 2.31+/-0.15 ml/kg/mm Hg in vehicle, P<0.05) without changing the unstressed volume (37.2+/-2.80 in T-1032 vs. 42.6+/-2.37 ml/kg in vehicle, P>0.05). It was concluded that T-1032 increased venous capacitance by increasing venous compliance, and that this selective phosphodiesterase type 5 inhibitor appeared to have a different vasodilator action from that of an NO donor and a Ca(2+) channel antagonist in that it had a selective action on the mean circulatory filling pressure.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
422
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
109-14
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed-meshheading:11430921-Anesthesia, pubmed-meshheading:11430921-Animals, pubmed-meshheading:11430921-Blood Pressure, pubmed-meshheading:11430921-Diltiazem, pubmed-meshheading:11430921-Dose-Response Relationship, Drug, pubmed-meshheading:11430921-Ganglionic Blockers, pubmed-meshheading:11430921-Heart Rate, pubmed-meshheading:11430921-Isoquinolines, pubmed-meshheading:11430921-Male, pubmed-meshheading:11430921-Mecamylamine, pubmed-meshheading:11430921-Nitroglycerin, pubmed-meshheading:11430921-Norepinephrine, pubmed-meshheading:11430921-Phosphodiesterase Inhibitors, pubmed-meshheading:11430921-Pyridines, pubmed-meshheading:11430921-Rats, pubmed-meshheading:11430921-Rats, Wistar, pubmed-meshheading:11430921-Vasoconstrictor Agents, pubmed-meshheading:11430921-Vasodilator Agents, pubmed-meshheading:11430921-Venous Pressure
pubmed:year
2001
pubmed:articleTitle
T-1032, a novel specific phosphodiesterase type 5 inhibitor, increases venous compliance in anesthetized rats.
pubmed:affiliation
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., 2-2-50, Kawagishi Toda, Saitama, 335-8505, Japan. inoue-h@tanabe.co.jp
pubmed:publicationType
Journal Article