Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1991 Jun;103(2):1585–1591. doi: 10.1111/j.1476-5381.1991.tb09831.x

Cardiac haemodynamic effects of the non-peptide, angiotensin II-receptor antagonist, DuP 753, in conscious Long Evans and Brattleboro rats.

P Batin 1, S M Gardiner 1, A M Compton 1, P A Kemp 1, T Bennett 1
PMCID: PMC1908375  PMID: 1884112

Abstract

1. In previous experiments in conscious, water-replete Long Evans and Brattleboro rats the non-peptide angiotensin II-receptor antagonist, DuP 753, caused only slight hypotension and peripheral (particularly renal) vasodilatations. However in water-deprived (i.e. renin-dependent) Brattleboro rats, DuP 753 caused marked hypotension and regional vasodilatations. The major objective of the present study was to determine if the hypotensive effects of DuP 753 under any of the experimental conditions studied previously were contributed to by negative effects on cardiac haemodynamics. 2. Male, Long Evans and Brattleboro rats were chronically instrumented with electromagnetic flow probes on the ascending aorta and with intravascular catheters. Data were collected by use of a microcomputer-based system that provided digitised print-out of instantaneous heart rate, mean arterial blood pressure, cardiac output, stroke volume, peak aortic flow, maximum positive slope of the aortic flow signal (+ dF/dtmax), total peripheral conductance and central venous pressure. 3. Incremental i.v. bolus doses (0.1-10 mg kg-1, at 15 min intervals) of DuP 753 were administered to water-replete Long Evans (n = 8) and Brattleboro (n = 8) rats, and to water-deprived (14 h) Brattleboro rats (n = 9) (the latter animals show marked activation of the renin-angiotensin system). In all groups, 15 min after the highest dose of DuP 753 had been given, a supramaximal dose of captopril (2 mg kg-1) was injected to determine if it had any additional effects. 4. In water-replete, Long Evans and Brattleboro rats, DuP 753 (0.1-1 mg kg-1) caused slight, transient hypotension, with rises in total peripheral conductance; increases in cardiac output, peak aortic flow, + dF/dtmax and stroke volume were inconsistent and central venous pressure did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
1587

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Batin P., Gardiner S. M., Compton A. M., Bennett T. Differential regional haemodynamic effects of the non-peptide angiotensin II antagonist, DuP 753, in water-replete and water-deprived Brattleboro rats. Life Sci. 1991;48(8):733–739. doi: 10.1016/0024-3205(91)90087-r. [DOI] [PubMed] [Google Scholar]
  2. Bennett T., Gardiner S. M. Water deprivation: effects on fluid and electrolyte handling and plasma biochemistry in Long-Evans and Brattleboro rats. J Physiol. 1987 Apr;385:35–48. doi: 10.1113/jphysiol.1987.sp016482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chiu A. T., Herblin W. F., McCall D. E., Ardecky R. J., Carini D. J., Duncia J. V., Pease L. J., Wong P. C., Wexler R. R., Johnson A. L. Identification of angiotensin II receptor subtypes. Biochem Biophys Res Commun. 1989 Nov 30;165(1):196–203. doi: 10.1016/0006-291x(89)91054-1. [DOI] [PubMed] [Google Scholar]
  4. Chiu A. T., McCall D. E., Price W. A., Wong P. C., Carini D. J., Duncia J. V., Wexler R. R., Yoo S. E., Johnson A. L., Timmermans P. B. Nonpeptide angiotensin II receptor antagonists. VII. Cellular and biochemical pharmacology of DuP 753, an orally active antihypertensive agent. J Pharmacol Exp Ther. 1990 Feb;252(2):711–718. [PubMed] [Google Scholar]
  5. Gardiner S. M., Bennett T. Cardiac baroreflex sensitivities in conscious, unrestrained, Long Evans and Brattleboro rats. J Auton Nerv Syst. 1988 Sep;23(3):213–219. doi: 10.1016/0165-1838(88)90096-3. [DOI] [PubMed] [Google Scholar]
  6. Gardiner S. M., Bennett T. Interactions between neural mechanisms, the renin-angiotensin system and vasopressin in the maintenance of blood pressure during water deprivation: studies in Long Evans and Brattleboro rats. Clin Sci (Lond) 1985 Jun;68(6):647–657. doi: 10.1042/cs0680647. [DOI] [PubMed] [Google Scholar]
  7. Gardiner S. M., Compton A. M., Bennett T., Hartley C. J. Can pulsed Doppler technique measure changes in aortic blood flow in conscious rats? Am J Physiol. 1990 Aug;259(2 Pt 2):H448–H456. doi: 10.1152/ajpheart.1990.259.2.H448. [DOI] [PubMed] [Google Scholar]
  8. Gardiner S. M., Compton A. M., Kemp P. A., Bennett T. Cardiac output effects of endothelin-1, -2 and -3 and sarafotoxin S6b in conscious rats. J Auton Nerv Syst. 1990 Jun;30(2):143–147. doi: 10.1016/0165-1838(90)90138-9. [DOI] [PubMed] [Google Scholar]
  9. Gardiner S. M., Compton A. M., Kemp P. A., Bennett T. Regional and cardiac haemodynamic effects of NG-nitro-L-arginine methyl ester in conscious, Long Evans rats. Br J Pharmacol. 1990 Nov;101(3):625–631. doi: 10.1111/j.1476-5381.1990.tb14131.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hirakata H., Fouad-Tarazi F. M., Bumpus F. M., Khosla M., Healy B., Husain A., Urata H., Kumagai H. Angiotensins and the failing heart. Enhanced positive inotropic response to angiotensin I in cardiomyopathic hamster heart in the presence of captopril. Circ Res. 1990 Apr;66(4):891–899. doi: 10.1161/01.res.66.4.891. [DOI] [PubMed] [Google Scholar]
  11. Lindpaintner K., Jin M. W., Niedermaier N., Wilhelm M. J., Ganten D. Cardiac angiotensinogen and its local activation in the isolated perfused beating heart. Circ Res. 1990 Sep;67(3):564–573. doi: 10.1161/01.res.67.3.564. [DOI] [PubMed] [Google Scholar]
  12. Muller A. F., Gardiner S. M., Compton A. M., Bennett T. Regional haemodynamic effects of captopril, enalaprilat and lisinopril in conscious water-replete and water-deprived Brattleboro rats. Clin Sci (Lond) 1990 Oct;79(4):393–401. doi: 10.1042/cs0790393. [DOI] [PubMed] [Google Scholar]
  13. Smith T. L., Hutchins P. M. Central hemodynamics in the developmental stage of spontaneous hypertension in the unanesthetized rat. Hypertension. 1979 Sep-Oct;1(5):508–517. doi: 10.1161/01.hyp.1.5.508. [DOI] [PubMed] [Google Scholar]
  14. Smits J. F., Coleman T. G., Smith T. L., Kasbergen C. M., van Essen H., Struyker-Boudier H. A. Antihypertensive effect of propranolol in conscious spontaneously hypertensive rats: central hemodynamics, plasma volume, and renal function during beta-blockade with propranolol. J Cardiovasc Pharmacol. 1982 Nov-Dec;4(6):903–914. doi: 10.1097/00005344-198211000-00005. [DOI] [PubMed] [Google Scholar]
  15. Tomlinson K. C., Gardiner S. M., Bennett T. Hypotensive effects of angiotensin II analogues and angiotensin converting enzyme inhibitors in water-deprived Brattleboro rats. J Cardiovasc Pharmacol. 1990 Apr;15(4):562–568. doi: 10.1097/00005344-199004000-00006. [DOI] [PubMed] [Google Scholar]
  16. Urata H., Healy B., Stewart R. W., Bumpus F. M., Husain A. Angiotensin II-forming pathways in normal and failing human hearts. Circ Res. 1990 Apr;66(4):883–890. doi: 10.1161/01.res.66.4.883. [DOI] [PubMed] [Google Scholar]
  17. Whitebread S., Mele M., Kamber B., de Gasparo M. Preliminary biochemical characterization of two angiotensin II receptor subtypes. Biochem Biophys Res Commun. 1989 Aug 30;163(1):284–291. doi: 10.1016/0006-291x(89)92133-5. [DOI] [PubMed] [Google Scholar]
  18. Wong P. C., Hart S. D., Zaspel A. M., Chiu A. T., Ardecky R. J., Smith R. D., Timmermans P. B. Functional studies of nonpeptide angiotensin II receptor subtype-specific ligands: DuP 753 (AII-1) and PD123177 (AII-2). J Pharmacol Exp Ther. 1990 Nov;255(2):584–592. [PubMed] [Google Scholar]
  19. Wong P. C., Price W. A., Chiu A. T., Duncia J. V., Carini D. J., Wexler R. R., Johnson A. L., Timmermans P. B. Nonpeptide angiotensin II receptor antagonists. VIII. Characterization of functional antagonism displayed by DuP 753, an orally active antihypertensive agent. J Pharmacol Exp Ther. 1990 Feb;252(2):719–725. [PubMed] [Google Scholar]
  20. Zusman R. M. Renin- and non-renin-mediated antihypertensive actions of converting enzyme inhibitors. Kidney Int. 1984 Jun;25(6):969–983. doi: 10.1038/ki.1984.119. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES