Urotensin-II: a novel systemic hypertensive factor in the cat

被引:32
作者
Behm, DJ [1 ]
Doe, CPA [1 ]
Johns, DG [1 ]
Maniscalco, K [1 ]
Stankus, GP [1 ]
Wibberley, A [1 ]
Willette, RN [1 ]
Douglas, SA [1 ]
机构
[1] GlaxoSmithKline, Cardiovasc & Urogenital Ctr Excellence Drug Disco, King Of Prussia, PA 19406 USA
关键词
urotensin-II; GPR14; UT; vasoconstriction; vascular resistance; blood pressure; hypertension; mesenteric arteries;
D O I
10.1007/s00210-004-0873-1
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Urotensin-II, a potent mammalian vasoconstrictor, may play a role in the etiology of essential hypertension. However, a species suitable for assessing such a role, one where a "classical" systemic hypertensive response (increase in mean blood pressure and systemic vascular resistance) is observed following bolus i.v. urotensin-II administration, has yet to be identified. The present study demonstrates that the cat may represent such a species since urotensin-II potently (pEC(50)s 9.68+/-0.24-8.73+/-0.08) and efficaciously (E-max 73+/-15%-205+/-21% KCl) constricts all feline isolated arteries studied (aortae, renal, femoral, carotid, and mesenteric conduit/resistance). Accordingly, exogenous urotensin-II (1 nmol/kg, i.v.) effectively doubles both mean blood pressure (from 99+/-14 to 183+/-15 mmHg) and systemic vascular resistance (from 0.36+/-0.12 to 0.86+/-0.20 mmHg/ml/min) in the anaesthetized cat (without altering heart rate or stroke volume). Thus, in view of these profound contractile effects, the cat could be suitable for determining the effects of urotensin-II receptor antagonism on cardiovascular homeostasis in both normal and diseased states.
引用
收藏
页码:274 / 280
页数:7
相关论文
共 33 条
  • [1] No effect on central or peripheral blood pressure of systemic urotensin II infusion in humans
    Affolter, JT
    Newby, DE
    Wilkinson, IB
    Winter, MJ
    Balment, RJ
    Webb, DJ
    [J]. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2002, 54 (06) : 617 - 621
  • [2] Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14
    Ames, RS
    Sarau, HM
    Chambers, JK
    Willette, RN
    Alyar, NV
    Romanic, AM
    Louden, CS
    Foley, JJ
    Sauermelch, CF
    Coatney, RW
    Ao, ZH
    Disa, J
    Holmes, SD
    Stadel, JM
    Martin, JD
    Liu, WS
    Glover, GI
    Wilson, S
    McNulty, DE
    Ellis, CE
    Elshourbagy, NA
    Shabon, U
    Trill, JJ
    Hay, DWP
    Ohlstein, EH
    Bergsma, DJ
    Douglas, SA
    [J]. NATURE, 1999, 401 (6750) : 282 - 286
  • [3] [Anonymous], 1985, GUIDE CARE USE LAB A
  • [4] Deletion of the UT receptor gene results in the selective loss of urotensin-II contractile activity in aortae isolated from UT receptor knockout mice
    Behm, DJ
    Harrison, SM
    Ao, ZH
    Maniscalco, K
    Pickering, SJ
    Grau, EV
    Woods, TN
    Coatney, RW
    Doe, CPA
    Willette, RN
    Johns, DG
    Douglas, SA
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 2003, 139 (02) : 464 - 472
  • [5] Urotensin II evokes potent vasoconstriction in humans in vivo
    Böhm, F
    Pernow, J
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 2002, 135 (01) : 25 - 27
  • [6] Human urotensin-II is an endothelium-dependent vasodilator in rat small arteries
    Bottrill, FE
    Douglas, SA
    Hiley, CR
    White, R
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 2000, 130 (08) : 1865 - 1870
  • [7] Effects of human urotensin II in isolated vessels of various species;: comparison with other vasoactive agents
    Camarda, V
    Rizzi, A
    Calò, G
    Gendron, G
    Perron, SI
    Kostenis, E
    Zamboni, P
    Mascoli, F
    Regoli, D
    [J]. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2002, 365 (02) : 141 - 149
  • [8] Cloning, sequence analysis and tissue distribution of the mouse and rat urotensin II precursors
    Coulouarn, Y
    Jégou, S
    Tostivint, H
    Vaudry, H
    Lihrmann, I
    [J]. FEBS LETTERS, 1999, 457 (01) : 28 - 32
  • [9] Cloning of the cDNA encoding the urotensin II precursor in frog and human reveals intense expression of the urotensin II gene in motoneurons of the spinal cord
    Coulouarn, Y
    Lihrmann, I
    Jegou, S
    Anouar, Y
    Tostivint, H
    Beauvillain, JC
    Conlon, JM
    Bern, HA
    Vaudry, H
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (26) : 15803 - 15808
  • [10] Human urotensin-II as a novel cardiovascular target: 'heart' of the matter or simply a fishy 'tail'?
    Douglas, SA
    [J]. CURRENT OPINION IN PHARMACOLOGY, 2003, 3 (02) : 159 - 167