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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1987 Jan;90(1):61–70. doi: 10.1111/j.1476-5381.1987.tb16825.x

Effects of alpha-adrenoceptor agonists on cardiac output and its regional distribution in the pithed rat.

C R Hiley, G R Thomas
PMCID: PMC1917298  PMID: 2880628

Abstract

Cardiac output, its distribution and tissue blood flows were determined with tracer microspheres in pithed rats during pressor responses elicited by either alpha 1-adrenoceptor agonists (cirazoline, phenylephrine) or alpha 2-adrenoceptor agonists (xylaxine, B-HT 933). Two doses were used for each of cirazoline and B-HT 933 and phenylephrine was investigated in the presence of propranolol (3 mg kg-1). The rats were pithed under halothane anaesthesia. Cardiac output was increased by xylazine, the higher dose of B-HT 933 and phenylephrine. Heart rate was increased by phenylephrine and the higher doses of both cirazoline and B-HT 933. Stroke volume was greater in those groups given xylazine, phenylephrine and the higher dose of B-HT 933 but was decreased in those animals given the higher dose of cirazoline. Both alpha 2-adrenoceptor agonists increased the number of microspheres trapped in the lungs and the proportion of the cardiac output passing through the hepatic artery but decreased that flowing through the spleen and gastrointestinal tract. The higher dose of B-HT 933 also decreased the fraction of cardiac output flowing to the kidneys but kidney blood flow was maintained as a result of the increased cardiac output. Also, this treatment reduced blood flow in the epididimal fat pads. Both alpha 1-adrenoceptor agonists increased the fraction of cardiac output received by the coronary vasculature but the only other effect on distribution common to these agents was an increase in the percentage of the cardiac output passing to the hepatic artery. Cirazoline decreased the proportion of cardiac output distributed to the gastrointestinal tract and spleen but the total fraction of cardiac output passing to the hepatosplanchnic region was maintained as a result of the increase to the hepatic artery. Cirazoline markedly reduced the proportion of the cardiac output received by the kidneys and absolute flow in these organs was only 1.4% of control after the higher dose of this agonist but flow at the lower dose was maintained by the higher cardiac output. It is concluded that there is a significant contribution to the pressor responses elicited by alpha-agonists resulting from an alpha-adrenoceptor-mediated increase in cardiac output that may result from greater heart rates or stroke volumes. Also, there is a differential distribution of alpha-receptor subtypes throughout the vasculature which is especially noticeable in the kidneys.

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Selected References

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  1. Agrawal D. K., Daniel E. E. Two distinct populations of [3H]prazosin and [3H]yohimbine binding sites in the plasma membranes of rat mesenteric artery. J Pharmacol Exp Ther. 1985 Apr;233(1):195–203. [PubMed] [Google Scholar]
  2. Digges K. G., Summers R. J. Characterization of postsynaptic alpha-adrenoceptors in rat aortic strips and portal veins. Br J Pharmacol. 1983 Jul;79(3):655–665. doi: 10.1111/j.1476-5381.1983.tb10002.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Docherty J. R., McGrath J. C. A comparison of pre- and post-junctional potencies of several alpha-adrenoceptor agonists in the cardiovascular system and anococcygeus muscle of the rat. Evidence for two types of post-junctional alpha-adrenoceptor. Naunyn Schmiedebergs Arch Pharmacol. 1980 Jun;312(2):107–116. doi: 10.1007/BF00569718. [DOI] [PubMed] [Google Scholar]
  4. Drew G. M., Whiting S. B. Evidence for two distinct types of postsynaptic alpha-adrenoceptor in vascular smooth muscle in vivo. Br J Pharmacol. 1979 Oct;67(2):207–215. doi: 10.1111/j.1476-5381.1979.tb08668.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Eikenburg D. C. Functional characterization of the pre- and postjunctional alpha-adrenoceptors in the in situ perfused rat mesenteric vascular bed. Eur J Pharmacol. 1984 Oct 1;105(1-2):161–165. doi: 10.1016/0014-2999(84)90661-7. [DOI] [PubMed] [Google Scholar]
  6. Flavahan N. A., Grant T. L., Greig J., McGrath J. C. Analysis of the alpha-adrenoceptor-mediated, and other, components in the sympathetic vasopressor responses of the pithed rat. Br J Pharmacol. 1985 Sep;86(1):265–274. doi: 10.1111/j.1476-5381.1985.tb09458.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gardiner J. C., Peters C. J. Postsynaptic alpha 1-and alpha 2-adrenoceptor involvement in the vascular responses to neuronally released and exogenous noradrenaline in the hindlimb of the dog and cat. Eur J Pharmacol. 1982 Oct 22;84(3-4):189–198. doi: 10.1016/0014-2999(82)90201-1. [DOI] [PubMed] [Google Scholar]
  8. Gerold M., Haeusler G. alpha 2-Adrenoceptors in rat resistance vessels. Naunyn Schmiedebergs Arch Pharmacol. 1983 Feb;322(1):29–33. doi: 10.1007/BF00649348. [DOI] [PubMed] [Google Scholar]
  9. Hesse I. F., Johns E. J. An in vivo study of the alpha-adrenoreceptor subtypes on the renal vasculature of the anaesthetized rabbit. J Auton Pharmacol. 1984 Sep;4(3):145–152. doi: 10.1111/j.1474-8673.1984.tb00091.x. [DOI] [PubMed] [Google Scholar]
  10. Horn P. T., Kohli J. D., Listinsky J. J., Goldberg L. I. Regional variation in the alpha-adrenergic receptors in the canine resistance vessels. Naunyn Schmiedebergs Arch Pharmacol. 1982 Feb;318(3):166–172. doi: 10.1007/BF00500476. [DOI] [PubMed] [Google Scholar]
  11. Hyman A. L., Kadowitz P. J. Evidence for existence of postjunctional alpha 1- and alpha 2-adrenoceptors in cat pulmonary vascular bed. Am J Physiol. 1985 Oct;249(4 Pt 2):H891–H898. doi: 10.1152/ajpheart.1985.249.4.H891. [DOI] [PubMed] [Google Scholar]
  12. Högestätt E. D., Andersson K. E. On the postjunctional alpha-adrenoreceptors in rat cerebral and mesenteric arteries. J Auton Pharmacol. 1984 Sep;4(3):161–173. doi: 10.1111/j.1474-8673.1984.tb00093.x. [DOI] [PubMed] [Google Scholar]
  13. Kakihana M., Noda H., Ohtsuka S., Sugishita Y., Ito I. Significant role of alpha 2-adrenoceptors in coronary artery spasm. Jpn Circ J. 1985 Jan;49(1):108–118. doi: 10.1253/jcj.49.108. [DOI] [PubMed] [Google Scholar]
  14. Kalkman H. O., Thoolen M. J., Timmermans P. B., van Zwieten P. A. The influence of alpha 1- and alpha 2-adrenoceptor agonists on cardiac output in rats and cats. J Pharm Pharmacol. 1984 Apr;36(4):265–268. doi: 10.1111/j.2042-7158.1984.tb04365.x. [DOI] [PubMed] [Google Scholar]
  15. McDevitt D. G., Nies A. S. Simultaneous measurement of cardiac output and its distribution with microspheres in the rat. Cardiovasc Res. 1976 Jul;10(4):494–498. doi: 10.1093/cvr/10.4.494. [DOI] [PubMed] [Google Scholar]
  16. McGrath J. C. Evidence for more than one type of post-junctional alpha-adrenoceptor. Biochem Pharmacol. 1982 Feb 15;31(4):467–484. doi: 10.1016/0006-2952(82)90147-2. [DOI] [PubMed] [Google Scholar]
  17. McGrath J. C., Flavahan N. A., McKean C. E. alpha 1- and alpha 2-Adrenoceptor-mediated pressor and chronotropic effects in the rat and rabbit. J Cardiovasc Pharmacol. 1982;4 (Suppl 1):S101–S107. doi: 10.1097/00005344-198200041-00021. [DOI] [PubMed] [Google Scholar]
  18. Nichols A. J., Hiley C. R. Identification of adrenoceptors and dopamine receptors mediating vascular responses in the superior mesenteric arterial bed of the rat. J Pharm Pharmacol. 1985 Feb;37(2):110–115. doi: 10.1111/j.2042-7158.1985.tb05017.x. [DOI] [PubMed] [Google Scholar]
  19. Ruffolo R. R., Jr, Waddell J. E., Yaden E. L. Postsynaptic alpha adrenergic receptor subtypes differentiated by yohimbine in tissues from the rat. Existence of alpha-2 adrenergic receptors in rat aorta. J Pharmacol Exp Ther. 1981 May;217(2):235–240. [PubMed] [Google Scholar]
  20. Schmitz J. M., Graham R. M., Sagalowsky A., Pettinger W. A. Renal alpha-1 and alpha-2 adrenergic receptors: biochemical and pharmacological correlations. J Pharmacol Exp Ther. 1981 Nov;219(2):400–406. [PubMed] [Google Scholar]
  21. Timmermans P. B., van Zwieten P. A. Mini-review. The postsynaptic alpha 2-adrenoreceptor. J Auton Pharmacol. 1981 Mar;1(2):171–183. doi: 10.1111/j.1474-8673.1981.tb00509.x. [DOI] [PubMed] [Google Scholar]
  22. Wagner J., Brodde O. E. On the presence and distribution of alpha-adrenoceptors in the heart of various mammalian species. Naunyn Schmiedebergs Arch Pharmacol. 1978 May;302(3):239–254. doi: 10.1007/BF00508293. [DOI] [PubMed] [Google Scholar]
  23. Waldron C. J., Hicks P. E. Relative contribution of different vascular beds to the pressor effects of alpha-adrenoreceptor agonists and vasopressin in pithed rats: radioactive microsphere determination. J Auton Pharmacol. 1985 Dec;5(4):333–338. doi: 10.1111/j.1474-8673.1985.tb00558.x. [DOI] [PubMed] [Google Scholar]
  24. Wolff D. W., Buckalew V. M., Jr, Strandhoy J. W. Renal alpha 1- and alpha 2-adrenoceptor mediated vasoconstriction in dogs: comparison of phenylephrine, clonidine, and guanabenz. J Cardiovasc Pharmacol. 1984;6 (Suppl 5):S793–S798. [PubMed] [Google Scholar]
  25. Yamamoto R., Kawasaki H., Takasaki K. Postsynaptic alpha-adrenoreceptor populations in several vascular systems of the anaesthetized rat. J Auton Pharmacol. 1984 Dec;4(4):231–239. doi: 10.1111/j.1474-8673.1984.tb00100.x. [DOI] [PubMed] [Google Scholar]
  26. van Meel J. C., de Jonge A., Timmermans P. B., van Zwieten P. A. Selectivity of some alpha adrenoceptor agonists for peripheral alpha-1 and alpha-2 adrenoceptors in the normotensive rat. J Pharmacol Exp Ther. 1981 Dec;219(3):760–767. [PubMed] [Google Scholar]

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