Effects of potassium channel opener aprikalim on the receptor-mediated vasoconstriction in the human internal mammary artery. 2001

M H Liu, and H S Floten, and A P Furnary, and A P Yim, and G W He
Cardiovascular Research, Starr Academic Center for Cardiac Surgery, Providence Heart Institute, St Vincent Hospital, Portland, Oregon, USA.

BACKGROUND Arterial grafts for coronary artery bypass grafting such as the internal mammary artery (IMA) may develop spasm perioperatively. The purpose of this study was to investigate the effects of the potassium channel opener, aprikalim, on the receptor-mediated vasoconstriction in the human IMA in vitro. METHODS We studied 160 IMA rings taken from coronary artery surgery in organ baths. The interaction between aprikalim and four vasoconstrictors 5-hydroxytryptamine (5-HT), norepinephrine (NE), endothelin-1 (ET-1), and angiotensin II (AII) was investigated in two ways. RESULTS Aprikalim relaxed IMA rings precontracted by the vasoconstrictors to 66.40 +/- 5.9% for 5-HT (EC50: -6.78 +/- 0.26 LogM), 57.40 +/- 5.5% for NE (-6.54 +/- 0.39 LogM), 81.00 +/- 6.7% for ET-1 (-6.58 +/- 0.26 LogM), and 93.90 +/- 2.5% for AII (-7.80 +/- 0.23 LogM). The relaxation in endothelium-denuded rings contracted by AII was similar to that in the endothelium-intact rings. The relaxation was attenuated by glibenclamide (3 microM) in 5-HT or NE-precontracted IMA. Pretreatment with aprikalim at 1 microM depressed AII-induced contraction (33.20 +/- 7.5% versus 59.70 +/- 7.3%, p < 0.01) but only shifted the curves rightward for 5-HT or NE (EC50 3.1 or 4.3-folds higher, p < 0.05), whereas at 30 microM it also significantly depressed the maximal contraction for 5-HT (35.70 +/- 4.9% versus 103.30 +/- 9.8%, p < 0.001) and NE (90.60 +/- 15.6% versus 125.60 +/- 7.9%, p < 0.05). In contrast, aprikalim did not significantly depress the contraction induced by ET-1 (p > 0.05). CONCLUSIONS We conclude that aprikalim has vasorelaxant effects on IMA and the effect is vasoconstrictor-selective and endothelium-independent. Aprikalim may provide clinically useful vasorelaxant effects in coronary bypass surgery.

UI MeSH Term Description Entries
D008323 Mammary Arteries Arteries originating from the subclavian or axillary arteries and distributing to the anterior thoracic wall, mediastinal structures, diaphragm, pectoral muscles and mammary gland. Internal Mammary Artery,Internal Thoracic Artery,Arteries, Internal Mammary,Arteries, Internal Thoracic,Arteries, Mammary,Artery, Internal Mammary,Artery, Internal Thoracic,Artery, Mammary,Internal Mammary Arteries,Internal Thoracic Arteries,Mammary Arteries, Internal,Mammary Artery,Mammary Artery, Internal,Thoracic Arteries, Internal,Thoracic Artery, Internal
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D010847 Picolines A group of compounds that are monomethyl derivatives of pyridines. (From Dorland, 28th ed) Picoline
D011714 Pyrans Pyran
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000804 Angiotensin II An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS. Angiotensin II, Ile(5)-,Angiotensin II, Val(5)-,5-L-Isoleucine Angiotensin II,ANG-(1-8)Octapeptide,Angiotensin II, Isoleucine(5)-,Angiotensin II, Valine(5)-,Angiotensin-(1-8) Octapeptide,Isoleucine(5)-Angiotensin,Isoleucyl(5)-Angiotensin II,Valyl(5)-Angiotensin II,5 L Isoleucine Angiotensin II,Angiotensin II, 5-L-Isoleucine
D012701 Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator. 5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine
D014661 Vasoconstriction The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE. Vasoconstrictions
D014665 Vasodilator Agents Drugs used to cause dilation of the blood vessels. Vasoactive Antagonists,Vasodilator,Vasodilator Agent,Vasodilator Drug,Vasorelaxant,Vasodilator Drugs,Vasodilators,Vasorelaxants,Agent, Vasodilator,Agents, Vasodilator,Antagonists, Vasoactive,Drug, Vasodilator,Drugs, Vasodilator

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