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. 1994 Sep;113(1):129–136. doi: 10.1111/j.1476-5381.1994.tb16184.x

Effects of chronic infusions of alpha-trinositol on regional and cardiac haemodynamics in conscious rats.

S M Gardiner 1, P A Kemp 1, B Fallgren 1, T Bennett 1
PMCID: PMC1510081  PMID: 7812602

Abstract

1. Male, Long Evans rats (350-450 g) were chronically instrumented for the measurement of renal, mesenteric and hindquarters haemodynamics, and were given three consecutive, 24 h infusions of vehicle (sterile saline at 0.3 ml h-1, n = 8) or alpha-trinositol (D-myo-inositol-1,2,6-triphosphate) at 5, 20 and 80 mg kg-1 h-1 (0.3 ml h-1; n = 9). During infusion of alpha-trinositol at 5 or 20 mg kg-1 h-1, cardiovascular changes were little different from those seen during saline infusion. However, during infusion of alpha-trinositol at 80 mg kg-1 h-1 there were increases in hindquarters vascular conductance, renal flow and vascular conductance, that were all significantly different from the changes seen in the saline group. Infusion of alpha-trinositol at the high dose in naive rats (n = 8) had even more marked vasodilator effects. 2. Two groups of rats (n = 8 in each), chronically instrumented for the measurement of cardiac haemodynamics, were given 48 h infusions of saline (0.3 ml h-1) or alpha-trinositol (2 mg kg-1 bolus, 80 mg kg-1 h-1 infusion at 0.3 ml h-1). During the infusion of saline, there were slight reductions in heart rate, cardiac index, peak aortic flow, dF/dtmax and central venous pressure. In the animals receiving alpha-trinositol, with the exception of central venous pressure, all the above variables, together with total peripheral conductance, increased. 3. These results, collectively, indicate that incremental infusions of alpha-trinositol do not reveal its full vasodilator potential, possibly due to concurrent activation of counter-regulatory vasoconstrictor mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Adamsson M., Edvinsson L. Blockade of neuropeptide Y-induced potentiation of noradrenaline-evoked vasoconstriction by D-myo-inositol-1.2.6-trisphosphate (PP56) in rabbit femoral arteries. Neuropeptides. 1991 May;19(1):13–16. doi: 10.1016/0143-4179(91)90068-t. [DOI] [PubMed] [Google Scholar]
  2. Carrington A. L., Calcutt N. A., Ettlinger C. B., Gustafsson T., Tomlinson D. R. Effects of treatment with myo-inositol or its 1,2,6-trisphosphate (PP56) on nerve conduction in streptozotocin-diabetes. Eur J Pharmacol. 1993 Jun 24;237(2-3):257–263. doi: 10.1016/0014-2999(93)90277-o. [DOI] [PubMed] [Google Scholar]
  3. Donoso M. V., Boric M., Prado M., Fournier A., St Pierre S., Edvinsson L., Huidobro-Toro J. P. D-myo-inositol 1,2,6-trisphosphate blocks neuropeptide Y-induced facilitation of noradrenaline-evoked vasoconstriction of the mesenteric bed. Eur J Pharmacol. 1993 Aug 10;240(1):93–97. doi: 10.1016/0014-2999(93)90552-s. [DOI] [PubMed] [Google Scholar]
  4. Edvinsson L., Adamsson M., Jansen I. Neuropeptide Y antagonistic properties of D-myo-inositol-1.2.6-trisphosphate in guinea pig basilar arteries. Neuropeptides. 1990 Oct;17(2):99–105. doi: 10.1016/0143-4179(90)90056-5. [DOI] [PubMed] [Google Scholar]
  5. Edvinsson L., Adamsson M. Neuropeptide Y inhibits relaxation of guinea pig cerebral, coronary, and uterine arteries: blockade by D-myo-inositol-1,2,6-triphosphate. J Cardiovasc Pharmacol. 1992 Sep;20(3):466–472. doi: 10.1097/00005344-199209000-00019. [DOI] [PubMed] [Google Scholar]
  6. Feth F., Erdbrügger W., Rascher W., Michel M. C. Is PP56 (D-myo-inositol-1,2,6-trisphosphate) an antagonist at neuropeptide Y receptors? Life Sci. 1993;52(23):1835–1844. doi: 10.1016/0024-3205(93)90003-l. [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., Bennett T. Regional hemodynamic effects of calcitonin gene-related peptide. Am J Physiol. 1989 Feb;256(2 Pt 2):R332–R338. doi: 10.1152/ajpregu.1989.256.2.R332. [DOI] [PubMed] [Google Scholar]
  9. Gardiner S. M., Compton A. M., Kemp P. A., Bennett T., Foulkes R., Hughes B. Regional haemodynamic effects of prolonged infusions of human alpha-calcitonin gene-related peptide in conscious, Long Evans rats. Br J Pharmacol. 1991 Jun;103(2):1509–1514. doi: 10.1111/j.1476-5381.1991.tb09818.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gardiner S. M., Compton A. M., Kemp P. A., Bennett T., Hughes B., Foulkes R. Differential effects of (+/-)-dobutamine and human alpha-CGRP on cardiac and on regional haemodynamics in conscious Long Evans rats. Br J Pharmacol. 1991 Jun;103(2):1500–1508. doi: 10.1111/j.1476-5381.1991.tb09817.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gardiner S. M., Compton A. M., Kemp P. A., Bennett T. Regional and cardiac haemodynamic responses to glyceryl trinitrate, acetylcholine, bradykinin and endothelin-1 in conscious rats: effects of NG-nitro-L-arginine methyl ester. Br J Pharmacol. 1990 Nov;101(3):632–639. doi: 10.1111/j.1476-5381.1990.tb14132.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gardiner S. M., Kemp P. A., Bennett T. Effects of NG-nitro-L-arginine methyl ester on vasodilator responses to adrenaline or BRL 38227 in conscious rats. Br J Pharmacol. 1991 Nov;104(3):731–737. doi: 10.1111/j.1476-5381.1991.tb12496.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kulka P. J., Tryba M. Inotropic support of the critically ill patient. A review of the agents. Drugs. 1993 May;45(5):654–667. doi: 10.2165/00003495-199345050-00003. [DOI] [PubMed] [Google Scholar]
  14. Pernow J., Modin A., Lundberg J. M. No effect of D-myo-inositol-1,2,6-triphosphate on vasoconstriction evoked by neuropeptide Y and non-adrenergic sympathetic nerve stimulation. Eur J Pharmacol. 1992 Nov 3;222(1):171–174. doi: 10.1016/0014-2999(92)90836-s. [DOI] [PubMed] [Google Scholar]
  15. Potter E. K., Edvinsson L., Gustafsson T. Antagonism of pre- and postjunctional responses to neuropeptide Y and sympathetic stimulation by D-myo-inositol-1,2,6-trisphosphate in the anaesthetised dog. Eur J Pharmacol. 1992 Oct 20;221(2-3):307–314. doi: 10.1016/0014-2999(92)90717-i. [DOI] [PubMed] [Google Scholar]
  16. Ruf J. C., Ciavatti M., Gustafsson T., Renaud S. Effects of PP-56 and vitamin E on platelet hyperaggregability, fatty acid abnormalities, and clinical manifestations in streptozocin-induced diabetic rats. Diabetes. 1991 Feb;40(2):233–239. doi: 10.2337/diab.40.2.233. [DOI] [PubMed] [Google Scholar]
  17. Schwieler J. H., Hjemdahl P. D-myo-inositol-1,2,6-triphosphate (PP56) antagonizes nonadrenergic sympathetic vasoconstriction: possible involvement of neuropeptide Y. J Cardiovasc Pharmacol. 1993 Mar;21(3):347–352. doi: 10.1097/00005344-199303000-00001. [DOI] [PubMed] [Google Scholar]
  18. Sun X. Y., Dahlöf C., Edvinsson L., Hedner T. D-myo-inositol-1,2,6-trisphosphate is a selective antagonist of neuropeptide Y-induced pressor responses in the pithed rat. Eur J Pharmacol. 1991 Nov 12;204(3):281–286. doi: 10.1016/0014-2999(91)90853-i. [DOI] [PubMed] [Google Scholar]
  19. Sun X. Y., Edvinsson L., Hedner T. Effects of d-myo-inositol-1,2,6-trisphosphate on neuropeptide Y-induced potentiation of various vasoconstrictor agents in the rat. J Pharmacol Exp Ther. 1992 Jun;261(3):1147–1152. [PubMed] [Google Scholar]
  20. Sun X. Y., Edvinsson L., Hedner T. Neuropeptide Y-induced pressor responses in spontaneously hypertensive and Wistar-Kyoto rats antagonized by D-myo-inositol-1,2,6-triphosphate (PP56). J Hypertens Suppl. 1991 Dec;9(6):S344–S345. [PubMed] [Google Scholar]
  21. Sun X., Edvinsson L., Hedner T. Cardiovascular effects of alpha-trinositol in spontaneously hypertensive and normotensive Wistar-Kyoto rats. J Hypertens. 1993 Sep;11(9):935–943. doi: 10.1097/00004872-199309000-00007. [DOI] [PubMed] [Google Scholar]
  22. Tarazi R. C., Dustan H. P., Bravo E. L., Niarchos A. P. Vasodilating drugs: contrasting haemodynamic effects. Clin Sci Mol Med Suppl. 1976 Dec;3:575s–578s. doi: 10.1042/cs051575s. [DOI] [PubMed] [Google Scholar]
  23. Theodorsson-Norheim E. Friedman and Quade tests: BASIC computer program to perform nonparametric two-way analysis of variance and multiple comparisons on ranks of several related samples. Comput Biol Med. 1987;17(2):85–99. doi: 10.1016/0010-4825(87)90003-5. [DOI] [PubMed] [Google Scholar]
  24. Trapani A. J., Smits G. J., McGraw D. E., McMahon E. G., Blaine E. H. Hemodynamic basis for the depressor activity of zaprinast, a selective cyclic GMP phosphodiesterase inhibitor. J Pharmacol Exp Ther. 1991 Jul 1;258(1):269–274. [PubMed] [Google Scholar]
  25. Wahlestedt C., Reis D. J., Yoo H., Adamsson M., Andersson D., Edvinsson L. A novel inositol phosphate selectively inhibits vasoconstriction evoked by the sympathetic co-transmitters neuropeptide Y (NPY) and adenosine triphosphate (ATP). Neurosci Lett. 1992 Aug 31;143(1-2):123–126. doi: 10.1016/0304-3940(92)90247-5. [DOI] [PubMed] [Google Scholar]
  26. de Wildt D. J., Sangster B. An evaluation of derived aortic flow parameters as indices of myocardial contractility in rats. J Pharmacol Methods. 1983 Aug;10(1):55–64. doi: 10.1016/0160-5402(83)90014-1. [DOI] [PubMed] [Google Scholar]

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