In vitro effects of antihypertensive drugs on thromboxane agonist (U46619)-induced vasocontriction in human internal mammary artery

K. A. Tanaka, F. Szlam, N. Katori, A. Tsuda, Jerrold H. Levy

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background. Hypertension is a major problem in the perioperative period of cardiac and non-cardiac surgery. The vascular endothelium plays a crucial role in modulating vascular tone by producing vasodilators as well as vasoconstrictors. Thromboxane A2 (TxA2), a prototypical vasoconstrictor produced by endothelium and platelets, may play an important role in the pathogenesis of hypertension and subsequent ischaemic events. Although multiple drugs are currently available to treat perioperative hypertension, there is a paucity of data comparing these agents. Therefore, we examined the in vitro vascular effects of commonly used antihypertensive drugs on human internal mammary artery (IMA) segments. Methods. Relaxation responses to adenosine (a nucleoside), enalaprilat (a competitive inhibitor of angiotensin-converting enzyme), fenoldopam (a DI-dopamine receptor agonist), hydralazine, labetalol (an α- and β-adrenergic blocker), nicardipine (a calcium channel blocker), nicorandil (K+-ATP channel opener), nitroglycerin (GTN, a nitrosovasodilator), and sodium nitroprusside (SNP, a nitrosovasodilator) were studied in IMA segments pre-contracted with the TxA2 analogue (U46619, 1.0×10-8 M). Effects of labetalol were also studied in IMA segments precontracted with norepinephrine (1.0×10-6 M). All drugs were added in a cumulative fashion (range 10-10 to 10-3 M). Results. All agents in the current study, with the exception of enalaprilat, dilated the IMA segments pre-contracted with U46619. Only GTN and SNP induced a complete (90-100%) relaxation. The order of efficacy of the in vitro relaxation was as follows: SNP, GTN, nicardipine, nicorandil, fenoldopam, hydralazine, adenosine, and labetalol. The potency was in the order of GTN, SNP, fenoldopam, nicorandil, hydralazine, adenosine, and nicardipine. Conclusions. Various antihypertensive agents are effective in attenuating U46619-induced IMA vasoconstriction, but the efficacy and potency differ. The in vitro vasodilation may not be simply extrapolated to the clinical efficacy or outcome of each antihypertensive therapy; however, our data provide additional grounds for the choice of antihypertensive medication. Further clinical studies are needed to help to fully elucidate the use of different antihypertensive agents and clinical outcomes.

Original languageEnglish
Pages (from-to)257-262
Number of pages6
JournalBritish Journal of Anaesthesia
Volume93
Issue number2
DOIs
Publication statusPublished - 2004 Aug
Externally publishedYes

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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Mammary Arteries
Thromboxanes
Antihypertensive Agents
Fenoldopam
Nicorandil
Labetalol
Nicardipine
Hydralazine
Single Nucleotide Polymorphism
Enalaprilat
Adenosine
Thromboxane A2
Vasoconstrictor Agents
Hypertension
Blood Vessels
Perioperative Period
Adrenergic Antagonists
Dopamine Agonists
Vascular Endothelium

Keywords

  • Agonists, thromboxane
  • Arterial pressure, antihypertensives
  • Arteries, internal mammary artery
  • Complications, vasoconstriction

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

In vitro effects of antihypertensive drugs on thromboxane agonist (U46619)-induced vasocontriction in human internal mammary artery. / Tanaka, K. A.; Szlam, F.; Katori, N.; Tsuda, A.; Levy, Jerrold H.

In: British Journal of Anaesthesia, Vol. 93, No. 2, 08.2004, p. 257-262.

Research output: Contribution to journalArticle

Tanaka, K. A. ; Szlam, F. ; Katori, N. ; Tsuda, A. ; Levy, Jerrold H. / In vitro effects of antihypertensive drugs on thromboxane agonist (U46619)-induced vasocontriction in human internal mammary artery. In: British Journal of Anaesthesia. 2004 ; Vol. 93, No. 2. pp. 257-262.
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abstract = "Background. Hypertension is a major problem in the perioperative period of cardiac and non-cardiac surgery. The vascular endothelium plays a crucial role in modulating vascular tone by producing vasodilators as well as vasoconstrictors. Thromboxane A2 (TxA2), a prototypical vasoconstrictor produced by endothelium and platelets, may play an important role in the pathogenesis of hypertension and subsequent ischaemic events. Although multiple drugs are currently available to treat perioperative hypertension, there is a paucity of data comparing these agents. Therefore, we examined the in vitro vascular effects of commonly used antihypertensive drugs on human internal mammary artery (IMA) segments. Methods. Relaxation responses to adenosine (a nucleoside), enalaprilat (a competitive inhibitor of angiotensin-converting enzyme), fenoldopam (a DI-dopamine receptor agonist), hydralazine, labetalol (an α- and β-adrenergic blocker), nicardipine (a calcium channel blocker), nicorandil (K+-ATP channel opener), nitroglycerin (GTN, a nitrosovasodilator), and sodium nitroprusside (SNP, a nitrosovasodilator) were studied in IMA segments pre-contracted with the TxA2 analogue (U46619, 1.0×10-8 M). Effects of labetalol were also studied in IMA segments precontracted with norepinephrine (1.0×10-6 M). All drugs were added in a cumulative fashion (range 10-10 to 10-3 M). Results. All agents in the current study, with the exception of enalaprilat, dilated the IMA segments pre-contracted with U46619. Only GTN and SNP induced a complete (90-100{\%}) relaxation. The order of efficacy of the in vitro relaxation was as follows: SNP, GTN, nicardipine, nicorandil, fenoldopam, hydralazine, adenosine, and labetalol. The potency was in the order of GTN, SNP, fenoldopam, nicorandil, hydralazine, adenosine, and nicardipine. Conclusions. Various antihypertensive agents are effective in attenuating U46619-induced IMA vasoconstriction, but the efficacy and potency differ. The in vitro vasodilation may not be simply extrapolated to the clinical efficacy or outcome of each antihypertensive therapy; however, our data provide additional grounds for the choice of antihypertensive medication. Further clinical studies are needed to help to fully elucidate the use of different antihypertensive agents and clinical outcomes.",
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T1 - In vitro effects of antihypertensive drugs on thromboxane agonist (U46619)-induced vasocontriction in human internal mammary artery

AU - Tanaka, K. A.

AU - Szlam, F.

AU - Katori, N.

AU - Tsuda, A.

AU - Levy, Jerrold H.

PY - 2004/8

Y1 - 2004/8

N2 - Background. Hypertension is a major problem in the perioperative period of cardiac and non-cardiac surgery. The vascular endothelium plays a crucial role in modulating vascular tone by producing vasodilators as well as vasoconstrictors. Thromboxane A2 (TxA2), a prototypical vasoconstrictor produced by endothelium and platelets, may play an important role in the pathogenesis of hypertension and subsequent ischaemic events. Although multiple drugs are currently available to treat perioperative hypertension, there is a paucity of data comparing these agents. Therefore, we examined the in vitro vascular effects of commonly used antihypertensive drugs on human internal mammary artery (IMA) segments. Methods. Relaxation responses to adenosine (a nucleoside), enalaprilat (a competitive inhibitor of angiotensin-converting enzyme), fenoldopam (a DI-dopamine receptor agonist), hydralazine, labetalol (an α- and β-adrenergic blocker), nicardipine (a calcium channel blocker), nicorandil (K+-ATP channel opener), nitroglycerin (GTN, a nitrosovasodilator), and sodium nitroprusside (SNP, a nitrosovasodilator) were studied in IMA segments pre-contracted with the TxA2 analogue (U46619, 1.0×10-8 M). Effects of labetalol were also studied in IMA segments precontracted with norepinephrine (1.0×10-6 M). All drugs were added in a cumulative fashion (range 10-10 to 10-3 M). Results. All agents in the current study, with the exception of enalaprilat, dilated the IMA segments pre-contracted with U46619. Only GTN and SNP induced a complete (90-100%) relaxation. The order of efficacy of the in vitro relaxation was as follows: SNP, GTN, nicardipine, nicorandil, fenoldopam, hydralazine, adenosine, and labetalol. The potency was in the order of GTN, SNP, fenoldopam, nicorandil, hydralazine, adenosine, and nicardipine. Conclusions. Various antihypertensive agents are effective in attenuating U46619-induced IMA vasoconstriction, but the efficacy and potency differ. The in vitro vasodilation may not be simply extrapolated to the clinical efficacy or outcome of each antihypertensive therapy; however, our data provide additional grounds for the choice of antihypertensive medication. Further clinical studies are needed to help to fully elucidate the use of different antihypertensive agents and clinical outcomes.

AB - Background. Hypertension is a major problem in the perioperative period of cardiac and non-cardiac surgery. The vascular endothelium plays a crucial role in modulating vascular tone by producing vasodilators as well as vasoconstrictors. Thromboxane A2 (TxA2), a prototypical vasoconstrictor produced by endothelium and platelets, may play an important role in the pathogenesis of hypertension and subsequent ischaemic events. Although multiple drugs are currently available to treat perioperative hypertension, there is a paucity of data comparing these agents. Therefore, we examined the in vitro vascular effects of commonly used antihypertensive drugs on human internal mammary artery (IMA) segments. Methods. Relaxation responses to adenosine (a nucleoside), enalaprilat (a competitive inhibitor of angiotensin-converting enzyme), fenoldopam (a DI-dopamine receptor agonist), hydralazine, labetalol (an α- and β-adrenergic blocker), nicardipine (a calcium channel blocker), nicorandil (K+-ATP channel opener), nitroglycerin (GTN, a nitrosovasodilator), and sodium nitroprusside (SNP, a nitrosovasodilator) were studied in IMA segments pre-contracted with the TxA2 analogue (U46619, 1.0×10-8 M). Effects of labetalol were also studied in IMA segments precontracted with norepinephrine (1.0×10-6 M). All drugs were added in a cumulative fashion (range 10-10 to 10-3 M). Results. All agents in the current study, with the exception of enalaprilat, dilated the IMA segments pre-contracted with U46619. Only GTN and SNP induced a complete (90-100%) relaxation. The order of efficacy of the in vitro relaxation was as follows: SNP, GTN, nicardipine, nicorandil, fenoldopam, hydralazine, adenosine, and labetalol. The potency was in the order of GTN, SNP, fenoldopam, nicorandil, hydralazine, adenosine, and nicardipine. Conclusions. Various antihypertensive agents are effective in attenuating U46619-induced IMA vasoconstriction, but the efficacy and potency differ. The in vitro vasodilation may not be simply extrapolated to the clinical efficacy or outcome of each antihypertensive therapy; however, our data provide additional grounds for the choice of antihypertensive medication. Further clinical studies are needed to help to fully elucidate the use of different antihypertensive agents and clinical outcomes.

KW - Agonists, thromboxane

KW - Arterial pressure, antihypertensives

KW - Arteries, internal mammary artery

KW - Complications, vasoconstriction

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