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. 1991 Jun;103(2):1500–1508. doi: 10.1111/j.1476-5381.1991.tb09817.x

Differential effects of (+/-)-dobutamine and human alpha-CGRP on cardiac and on regional haemodynamics in conscious Long Evans rats.

S M Gardiner 1, A M Compton 1, P A Kemp 1, T Bennett 1, B Hughes 1, R Foulkes 1
PMCID: PMC1908385  PMID: 1884104

Abstract

1. Comparisons were made of the full haemodynamic profiles of the known cardiostimulant, (+/-)-dobutamine, and the putative inotropic peptide, human alpha-calcitonin gene-related peptide (human alpha-CGRP), in conscious, chronically-instrumented Long Evans rats. Both substances were administered continuously i.v. for 60 min at two doses ((+/-)-dobutamine, 2 and 10 mumol kg-1 h-1; human alpha-CGRP, 0.15 and 1.5 nmol kg-1 h-1). 2. In spite of their similar (small) effects on mean arterial blood pressure, the low doses of (+/-)-dobutamine and human alpha-CGRP influenced cardiac haemodynamics differently. Thus, (+/-)-dobutamine caused an increase in cardiac index (due to a tachycardia), accompanied by rises in peak aortic flow, maximum rate of rise of aortic flow (dF/dtmax) and total peripheral conductance. However, the latter waned during the infusion, and after the infusion there was a significant systemic vasoconstriction and reductions in peak aortic flow, dF/dtmax and stroke index. Such 'off' effects following dobutamine infusion have not been described previously. The infusion of the lower dose of human alpha-CGRP caused only a transient fall in central venous pressure. 3. The rise in total peripheral conductance during infusion of the lower dose of (+/-)-dobutamine was associated with increases in hindquarters and common and internal carotid vascular conductances. The fall in total peripheral conductance after infusion was associated with renal vasoconstriction. Although there was no significant change in total peripheral conductance during the infusion of the lower dose of human alpha-CGRP there were hindquarters and carotid vasodilatations together with mesenteric vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Ando K., Pegram B. L., Frohlich E. D. Hemodynamic effects of calcitonin gene-related peptide in spontaneously hypertensive rats. Am J Physiol. 1990 Feb;258(2 Pt 2):R425–R429. doi: 10.1152/ajpregu.1990.258.2.R425. [DOI] [PubMed] [Google Scholar]
  2. Biro G. P., Douglas J. R., Keon W. J., Taichman G. C. Changes in regional blood flow distribution induced by infusions of dopexamine hydrochloride or dobutamine in anesthetized dogs. Am J Cardiol. 1988 Aug 11;62(5):30C–36C. doi: 10.1016/s0002-9149(88)80064-x. [DOI] [PubMed] [Google Scholar]
  3. Brown Z. W., Amit Z., Weeks J. R. Simple flow-thru swivel for infusions into unrestrained animals. Pharmacol Biochem Behav. 1976 Sep;5(3):363–365. doi: 10.1016/0091-3057(76)90090-3. [DOI] [PubMed] [Google Scholar]
  4. Crossman D., McEwan J., MacDermot J., MacIntyre I., Dollery C. T. Human calcitonin gene-related peptide activates adenylate cyclase and releases prostacyclin from human umbilical vein endothelial cells. Br J Pharmacol. 1987 Dec;92(4):695–701. doi: 10.1111/j.1476-5381.1987.tb11373.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dorszewski A., Müller-Beckmann B., Kling L., Sponer G. Haemodynamic profile of an inhibitor of phosphodiesterase III, adibendan (BM 14.478): comparison with nitroprusside and dobutamine in conscious dogs. Br J Pharmacol. 1990 Nov;101(3):686–690. doi: 10.1111/j.1476-5381.1990.tb14141.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Drexler H., Höing S., Faude F., Wollschläger H., Just H. Central and regional vascular hemodynamics following intravenous milrinone in the conscious rat: comparison with dobutamine. J Cardiovasc Pharmacol. 1987 May;9(5):563–569. doi: 10.1097/00005344-198705000-00010. [DOI] [PubMed] [Google Scholar]
  7. Fischer P., Burger A., Graefe K. H., Trendelenburg U. The effect of (+/-)-dobutamine on adrenergic nerve endings. Naunyn Schmiedebergs Arch Pharmacol. 1989 Jan-Feb;339(1-2):79–84. doi: 10.1007/BF00165130. [DOI] [PubMed] [Google Scholar]
  8. Gardiner S. M., Bennett T. Regional hemodynamic responses to adrenoceptor antagonism in conscious rats. Am J Physiol. 1988 Oct;255(4 Pt 2):H813–H824. doi: 10.1152/ajpheart.1988.255.4.H813. [DOI] [PubMed] [Google Scholar]
  9. Gardiner S. M., Compton A. M., Bennett T., Kemp P. A., Ney U. Synergistic internal carotid vasodilator effects of human alpha-calcitonin gene-related peptide and nimodipine in conscious rats. Br J Pharmacol. 1990 Apr;99(4):830–834. doi: 10.1111/j.1476-5381.1990.tb13015.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gardiner S. M., Compton A. M., Bennett T. Regional haemodynamic effects of human alpha- and beta-calcitonin gene-related peptide in conscious Wistar rats. Br J Pharmacol. 1989 Dec;98(4):1225–1232. doi: 10.1111/j.1476-5381.1989.tb12668.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Gennari C., Nami R., Agnusdei D., Bianchini C., Pavese G. Acute cardiovascular and renal effects of human calcitonin gene-related peptide. Am J Hypertens. 1989 Feb;2(2 Pt 2):45S–49S. doi: 10.1093/ajh/2.2.45s. [DOI] [PubMed] [Google Scholar]
  13. Gennari C., Nami R., Agnusdei D., Fischer J. A. Improved cardiac performance with human calcitonin gene related peptide in patients with congestive heart failure. Cardiovasc Res. 1990 Mar;24(3):239–241. doi: 10.1093/cvr/24.3.239. [DOI] [PubMed] [Google Scholar]
  14. Haywood J. R., Shaffer R. A., Fastenow C., Fink G. D., Brody M. J. Regional blood flow measurement with pulsed Doppler flowmeter in conscious rat. Am J Physiol. 1981 Aug;241(2):H273–H278. doi: 10.1152/ajpheart.1981.241.2.H273. [DOI] [PubMed] [Google Scholar]
  15. Jaski B. E., Peters C. Inotropic, vascular and neuroendocrine effects of dopexamine hydrochloride and comparison with dobutamine. Am J Cardiol. 1988 Aug 11;62(5):63C–67C. doi: 10.1016/s0002-9149(88)80070-5. [DOI] [PubMed] [Google Scholar]
  16. Kurtz A., Muff R., Born W., Lundberg J. M., Millberg B. I., Gnädinger M. P., Uehlinger D. E., Weidmann P., Hökfelt T., Fischer J. A. Calcitonin gene-related peptide is a stimulator of renin secretion. J Clin Invest. 1988 Aug;82(2):538–543. doi: 10.1172/JCI113629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lappe R. W., Slivjak M. J., Todt J. A., Wendt R. L. Hemodynamic effects of calcitonin gene-related peptide in conscious rats. Regul Pept. 1987 Dec;19(5-6):307–312. doi: 10.1016/0167-0115(87)90172-8. [DOI] [PubMed] [Google Scholar]
  18. Leier C. V., Heban P. T., Huss P., Bush C. A., Lewis R. P. Comparative systemic and regional hemodynamic effects of dopamine and dobutamine in patients with cardiomyopathic heart failure. Circulation. 1978 Sep;58(3 Pt 1):466–475. doi: 10.1161/01.cir.58.3.466. [DOI] [PubMed] [Google Scholar]
  19. Leier C. V., Webel J., Bush C. A. The cardiovascular effects of the continuous infusion of dobutamine in patients with severe cardiac failure. Circulation. 1977 Sep;56(3):468–472. doi: 10.1161/01.cir.56.3.468. [DOI] [PubMed] [Google Scholar]
  20. Liang C. S., Hood W. B., Jr Dobutamine infusion in conscious dogs with and without autonomic nervous system inhibition: effects on systemic hemodynamics, regional blood flows and cardiac metabolism. J Pharmacol Exp Ther. 1979 Dec;211(3):698–705. [PubMed] [Google Scholar]
  21. Maccarrone C., Malta E., Raper C. Beta-adrenoceptor selectivity of dobutamine: in vivo and in vitro studies. J Cardiovasc Pharmacol. 1984 Jan-Feb;6(1):132–141. [PubMed] [Google Scholar]
  22. Marshall I., Al-Kazwini S. J., Holman J. J., Craig R. K. Human alpha-calcitonin gene-related peptide (CGRP) is a potent vasodilator in human mesenteric vasculature. Br J Clin Pharmacol. 1988 Dec;26(6):691–695. doi: 10.1111/j.1365-2125.1988.tb05306.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. O'Rourke M. F. Vascular impedance in studies of arterial and cardiac function. Physiol Rev. 1982 Apr;62(2):570–623. doi: 10.1152/physrev.1982.62.2.570. [DOI] [PubMed] [Google Scholar]
  24. Robie N. W., Goldberg L. I. Comparative systemic and regional hemodynamic effects of dopamine and dobutamine. Am Heart J. 1975 Sep;90(3):340–345. doi: 10.1016/0002-8703(75)90323-3. [DOI] [PubMed] [Google Scholar]
  25. Ruffolo R. R., Jr, Messick K. Inotropic selectivity of dobutamine enantiomers in the pithed rat. J Pharmacol Exp Ther. 1985 Nov;235(2):344–348. [PubMed] [Google Scholar]
  26. Ruffolo R. R., Jr, Messick K. Systemic hemodynamic effects of dopamine, (+/-)-dobutamine and the (+)-and (-)-enantiomers of dobutamine in anesthetized normotensive rats. Eur J Pharmacol. 1985 Feb 26;109(2):173–181. doi: 10.1016/0014-2999(85)90418-2. [DOI] [PubMed] [Google Scholar]
  27. Ruffolo R. R., Jr, Morgan E. L. Interaction of the novel inotropic agent, ASL-7022, with alpha and beta adrenoceptors in the cardiovascular system of the pithed rat: comparison with dobutamine and dopamine. J Pharmacol Exp Ther. 1984 May;229(2):364–371. [PubMed] [Google Scholar]
  28. Ruffolo R. R., Jr The pharmacology of dobutamine. Am J Med Sci. 1987 Oct;294(4):244–248. doi: 10.1097/00000441-198710000-00005. [DOI] [PubMed] [Google Scholar]
  29. Ruffolo R. R., Jr, Yaden E. L. Vascular effects of the stereoisomers of dobutamine. J Pharmacol Exp Ther. 1983 Jan;224(1):46–50. [PubMed] [Google Scholar]
  30. Sirén A. L., Feuerstein G. Cardiovascular effects of rat calcitonin gene-related peptide in the conscious rat. J Pharmacol Exp Ther. 1988 Oct;247(1):69–78. [PubMed] [Google Scholar]
  31. 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]
  32. 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]
  33. Sonnenblick E. H., Frishman W. H., LeJemtel T. H. Dobutamine: a new synthetic cardioactive sympathetic amine. N Engl J Med. 1979 Jan 4;300(1):17–22. doi: 10.1056/NEJM197901043000105. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Törnebrandt K., Nobin A., Owman C. Contractile and dilatory action of neuropeptides on isolated human mesenteric blood vessels. Peptides. 1987 Mar-Apr;8(2):251–256. doi: 10.1016/0196-9781(87)90099-4. [DOI] [PubMed] [Google Scholar]
  36. Vatner S. F., McRitchie R. J., Braunwald E. Effects of dobutamine on left ventricular performance, coronary dynamics, and distribution of cardiac output in conscious dogs. J Clin Invest. 1974 May;53(5):1265–1273. doi: 10.1172/JCI107673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Wang B. C., Bie P., Leadley R. J., Jr, Goetz K. L. Cardiovascular effects of calcitonin gene-related peptide in conscious dogs. Am J Physiol. 1989 Oct;257(4 Pt 2):R726–R731. doi: 10.1152/ajpregu.1989.257.4.R726. [DOI] [PubMed] [Google Scholar]

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