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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1988 Apr;93(4):781–790. doi: 10.1111/j.1476-5381.1988.tb11463.x

Effect of artificial respiratory volume on the cardiovascular responses to an alpha 1- and an alpha 2-adrenoceptor agonist in the air-ventilated pithed rat.

M R MacLean 1, C R Hiley 1
PMCID: PMC1853908  PMID: 2898957

Abstract

1. The effect of varying artificial respiratory volume (at a fixed rate of 54 min-1) on cardiac output, its distribution and tissue blood flows were determined with tracer microspheres in control pithed rats or during pressor responses to either the alpha 1-adrenoceptor agonist phenylephrine or the alpha 2-agonist xylazine. Phenylephrine was investigated in the presence of propranolol (3 mg kg-1). The rats were pithed under halothane anaesthesia. 2. A respiratory volume of 15 ml kg-1 produced modest hypercapnia (PaCO2 = 47 mmHg), hypoxia (PaO2 = 60 mmHg) and acidosis (pH = 7.35) relative to control animals respired at 20 ml kg-1 (PaCO2 = 32 mmHg; PaO2 = 77 mmHg; pH = 7.47). In rats respired at 15 ml kg-1, total peripheral resistance was lower, and cardiac output greater (due to increased stroke volume), than in the controls. Lowering respiratory volume reduced distribution of cardiac output to the kidneys, increased it to the large intestine and also increased blood flow through the gastrointestinal tract, skin and spleen. A respiratory volume of 30 ml kg-1 gave mild hypocapnia (PaCO2 = 19 mmHg), hyperoxia (PaO2 = 101 mmHg) and alkalosis (pH = 7.59) compared to 20 ml kg-1 but had no effect on cardiac output distribution or organ blood flow although heart rate was 29% greater at 30 ml kg-1. 3. Xylazine (500 micrograms bolus followed by 100 micrograms min-1 infusion) at all three respiratory volumes gave well-sustained mean pressor responses of 62-64 mmHg by increasing both total peripheral resistance and cardiac output (resulting from increased stroke volume). It increased the proportion of cardiac output passing to the liver, reduced that going to the spleen and gastrointestinal tract and increased cardiac, renal and hepatosplanchnic blood flows. 4. The secondary, relatively sustained, pressor effect of phenylephrine (5 micrograms bolus followed by 0.4 micrograms min-1 infusion, i.v.) varied at the 3 respiratory volumes with mean values from 32 to 53 mmHg. This response was due to both increased total peripheral resistance and cardiac output (resulting from greater stroke volumes and/or heart rates). Phenylephrine increased the proportion of cardiac output passing to the gastrointestinal tract, heart, kidneys and hepatosplanchnic bed and increased cardiac, hepatosplanchnic, renal and gastrointestinal blood flows. 5. Respiratory volume had no effect on the cardiovascular effects of xylazine. However, respiratory volume modified the effects of phenylephrine on heart rate and changed the relative contributions of stroke volume and heart rate to the increased cardiac output.(ABSTRACT TRUNCATED AT 400 WORDS)

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Selected References

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  1. BING R. J. CARDIAC METABOLISM. Physiol Rev. 1965 Apr;45:171–213. doi: 10.1152/physrev.1965.45.2.171. [DOI] [PubMed] [Google Scholar]
  2. Beierholm E. A., Grantham R. N., O'Keefe D. D., Laver M. B., Daggett W. M. Effects of acid-base changes, hypoxia, and catecholamines on ventricular performance. Am J Physiol. 1975 May;228(5):1555–1561. doi: 10.1152/ajplegacy.1975.228.5.1555. [DOI] [PubMed] [Google Scholar]
  3. Comline R. S., Silver M. The development of the adrenal medulla of the foetal and new-born calf. J Physiol. 1966 Mar;183(2):305–340. doi: 10.1113/jphysiol.1966.sp007868. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Docherty J. R., MacDonald A., McGrath J. C. Further sub-classification of alpha-adrenoceptors in the cardiovascular system, vas deferens and anococcygeus of the rat [proceedings]. Br J Pharmacol. 1979 Nov;67(3):421P–422P. [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. 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]
  8. Flavahan N. A., McGrath J. C. alpha 1-adrenoceptors can mediate chronotropic responses in the rat heart. Br J Pharmacol. 1981 Jul;73(3):586–588. doi: 10.1111/j.1476-5381.1981.tb16791.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Grant T. L., McGrath J. C., O'Brien J. W. The influence of blood gases on alpha 1- and alpha 2- adrenoceptor-mediated pressor responses in the pithed rat. Br J Pharmacol. 1985 Sep;86(1):69–77. doi: 10.1111/j.1476-5381.1985.tb09436.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hainsworth R. Vascular capacitance: its control and importance. Rev Physiol Biochem Pharmacol. 1986;105:101–173. doi: 10.1007/BFb0034498. [DOI] [PubMed] [Google Scholar]
  11. Hammill S. C., Wagner W. W., Jr, Latham L. P., Frost W. W., Weil J. V. Autonomic cardiovascular control during hypoxia in the dog. Circ Res. 1979 Apr;44(4):569–575. doi: 10.1161/01.res.44.4.569. [DOI] [PubMed] [Google Scholar]
  12. Hiley C. R., Thomas G. R. Effects of alpha-adrenoceptor agonists on cardiac output and its regional distribution in the pithed rat. Br J Pharmacol. 1987 Jan;90(1):61–70. doi: 10.1111/j.1476-5381.1987.tb16825.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Johnson T. S., Young J. B., Landsberg L. Sympathoadrenal responses to acute and chronic hypoxia in the rat. J Clin Invest. 1983 May;71(5):1263–1272. doi: 10.1172/JCI110876. [DOI] [PMC free article] [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. Kaufman L. J., Vollmer R. R. Endogenous angiotensin II facilitates sympathetically mediated hemodynamic responses in pithed rats. J Pharmacol Exp Ther. 1985 Oct;235(1):128–134. [PubMed] [Google Scholar]
  16. Korstanje C., Mathy M. J., van Charldorp K., de Jonge A., van Zwieten P. A. Influence of respiratory acidosis or alkalosis on pressor responses mediated by alpha 1- and alpha 2-adrenoceptors in pithed normotensive rats. Naunyn Schmiedebergs Arch Pharmacol. 1985 Sep;330(3):187–192. doi: 10.1007/BF00572433. [DOI] [PubMed] [Google Scholar]
  17. Lee J. C., Werner J. C., Downing S. E. Adrenal contribution to cardiac responses elicited by acute hypoxia in piglets. Am J Physiol. 1980 Dec;239(6):H751–H755. doi: 10.1152/ajpheart.1980.239.6.H751. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. Müller-Ruchholtz E. R., Lösch H. M., Grund E., Lochner W. Effect of beta adrenergic receptor stimulation on integrated systemic venous bed. Pflugers Arch. 1977 Sep 16;370(3):247–251. doi: 10.1007/BF00585534. [DOI] [PubMed] [Google Scholar]
  21. NAHAS G. G., MATHER G. W., WARGO J. D., ADAMS W. L. Influence of acute hypoxia on sympathectomized and adrenalectomized dogs. Am J Physiol. 1954 Apr;177(1):13–15. doi: 10.1152/ajplegacy.1954.177.1.13. [DOI] [PubMed] [Google Scholar]
  22. Nahas G. G., Zagury D., Milhaud A., Manger W. M., Pappas G. D. Acidemia and catecholamine output of the isolated canine adrenal gland. Am J Physiol. 1967 Nov;213(5):1186–1192. doi: 10.1152/ajplegacy.1967.213.5.1186. [DOI] [PubMed] [Google Scholar]
  23. Oates H. F., Stoker L. M., Monaghan J. C., Stokes G. S. The beta-adrenoceptor controlling renin release. Arch Int Pharmacodyn Ther. 1978 Aug;234(2):205–213. [PubMed] [Google Scholar]
  24. PRICE H. L., HELRICH M. The effect of cyclopropane, diethyl ether, nitrous oxide, thiopental, and hydrogen ion concentration on the myocardial dunction of the dog heart-lung preparation. J Pharmacol Exp Ther. 1955 Oct;115(2):206–216. [PubMed] [Google Scholar]
  25. Rutlen D. L., Supple E. N., Powell W. J., Jr beta-Adrenergic regulation of total systemic intravascular volume in the dog. Circ Res. 1981 Jan;48(1):112–120. doi: 10.1161/01.res.48.1.112. [DOI] [PubMed] [Google Scholar]
  26. Sonnenblick E. H., Kirk E. S. Effects of hypoxia and ischemia on myocardial contraction. Alterations in the time course of force and ischemia-dependent inhomogeneity of contractility. Cardiology. 1971;56(1):302–313. doi: 10.1159/000169374. [DOI] [PubMed] [Google Scholar]
  27. Vollmer R. R., Meyers S. A., Ertel R. J., Murthy V. S. Diminished sympathetic responsiveness in nephrectomized rats-role of the renin angiotensin system. Clin Exp Hypertens A. 1984;6(5):993–1009. doi: 10.3109/10641968409044052. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Weinberger M. H., Aoi W., Henry D. P. Direct effect of beta-adrenergic stimulation on renin release by the rat kidney slice in vitro. Circ Res. 1975 Sep;37(3):318–324. doi: 10.1161/01.res.37.3.318. [DOI] [PubMed] [Google Scholar]
  30. Yamaguchi I., Kopin I. J. Plasma catecholamine and blood pressure responses to sympathetic stimulation in pithed rats. Am J Physiol. 1979 Sep;237(3):H305–H310. doi: 10.1152/ajpheart.1979.237.3.H305. [DOI] [PubMed] [Google Scholar]
  31. de Jonge A., Knape J. T., van Meel J. C., Kalkman H. O., Wilffert B., Thoolen M. J., Timmermanns P. B., van Zwieten P. A. Effect of converting enzyme inhibition and angiotensin receptor blockade on the vasoconstriction mediated by alpha 1-and alpha 2-adrenoceptor stimulation in pithed normotensive rats. Naunyn Schmiedebergs Arch Pharmacol. 1982 Dec;321(4):309–313. doi: 10.1007/BF00498519. [DOI] [PubMed] [Google Scholar]

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