Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1993 Apr;91(4):1429–1435. doi: 10.1172/JCI116347

Homologous upregulation of human arterial alpha-adrenergic responses by guanadrel.

R V Hogikyan 1, M A Supiano 1
PMCID: PMC288117  PMID: 8473492

Abstract

The purpose of this study was to test the hypothesis that there is homologous upregulation of arterial alpha-adrenergic responsiveness during suppression of sympathetic nervous system (SNS) activity in humans. 10 subjects (19-28 yr) were studied during placebo and when SNS activity was suppressed by guanadrel. Changes in forearm blood flow (FABF) mediated by the intraarterial infusion of norepinephrine (NE), angiotensin II (AII), and phentolamine were measured by plethysmography. During guanadrel compared with placebo, plasma NE levels (1.28 +/- 0.09-0.85 +/- 0.06 nM; P = 0.0001) and the extra vascular NE release rate derived from [3H]NE kinetics were lower (7.1 +/- 0.7-4.0 +/- 0.2 nmol/min per m2; P = 0.0004), suggesting suppression of SNS activity. During guanadrel, there was increased sensitivity in the FABF response to NE (analysis of variance P = 0.03). In contrast, there was no difference in the FABF response to AII (analysis of variance P = 0.81), suggesting that the upregulation observed to NE was homologous. The increase in FABF during phentolamine was similar during guanadrel compared with placebo (guanadrel: 141 +/- 37 vs. placebo; 187 +/- 27% increase; P = 0.33), suggesting that there was at least partial compensation to maintain constant endogenous arterial alpha-adrenergic tone. We conclude that there is homologous upregulation of arterial alpha-adrenergic responsiveness in humans when SNS activity is suppressed by guanadrel.

Full text

PDF
1429

Selected References

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

  1. ANTON A. H., SAYRE D. F. A study of the factors affecting the aluminum oxide-trihydroxyindole procedure for the analysis of catecholamines. J Pharmacol Exp Ther. 1962 Dec;138:360–375. [PubMed] [Google Scholar]
  2. Berman M. A postulate to aid in model building. J Theor Biol. 1963 May;4(3):229–236. doi: 10.1016/0022-5193(63)90001-8. [DOI] [PubMed] [Google Scholar]
  3. Bevan R. D., Tsuru H. Functional and structural changes in the rabbit ear artery after sympathetic denervation. Circ Res. 1981 Aug;49(2):478–485. doi: 10.1161/01.res.49.2.478. [DOI] [PubMed] [Google Scholar]
  4. Biollaz J., Brunner H. R., Gavras I., Waeber B., Gavras H. Antihypertensive therapy with MK 421: angiotensin II--renin relationships to evaluate efficacy of converting enzyme blockade. J Cardiovasc Pharmacol. 1982 Nov-Dec;4(6):966–972. [PubMed] [Google Scholar]
  5. Egan B., Panis R., Hinderliter A., Schork N., Julius S. Mechanism of increased alpha adrenergic vasoconstriction in human essential hypertension. J Clin Invest. 1987 Sep;80(3):812–817. doi: 10.1172/JCI113138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Evans M. I., Halter J. B., Porte D., Jr Comparison of double- and single-isotope enzymatic derivative methods for measuring catecholamines in human plasma. Clin Chem. 1978 Apr;24(4):567–570. [PubMed] [Google Scholar]
  7. Feldman R. D., Limbird L. E., Nadeau J., FitzGerald G. A., Robertson D., Wood A. J. Dynamic regulation of leukocyte beta adrenergic receptor-agonist interactions by physiological changes in circulating catecholamines. J Clin Invest. 1983 Jul;72(1):164–170. doi: 10.1172/JCI110954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Finnerty F. A., Jr, Brogden R. N. Guanadrel. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in hypertension. Drugs. 1985 Jul;30(1):22–31. doi: 10.2165/00003495-198530010-00005. [DOI] [PubMed] [Google Scholar]
  9. Flavahan N. A., Miller V. M., Aarhus L. L., Vanhoutte P. M. Denervation augments alpha-2 but not alpha-1 adrenergic responses in canine saphenous veins. J Pharmacol Exp Ther. 1987 Feb;240(2):589–593. [PubMed] [Google Scholar]
  10. Haber E., Koerner T., Page L. B., Kliman B., Purnode A. Application of a radioimmunoassay for angiotensin I to the physiologic measurements of plasma renin activity in normal human subjects. J Clin Endocrinol Metab. 1969 Oct;29(10):1349–1355. doi: 10.1210/jcem-29-10-1349. [DOI] [PubMed] [Google Scholar]
  11. Hokanson D. E., Sumner D. S., Strandness D. E., Jr An electrically calibrated plethysmograph for direct measurement of limb blood flow. IEEE Trans Biomed Eng. 1975 Jan;22(1):25–29. doi: 10.1109/tbme.1975.324535. [DOI] [PubMed] [Google Scholar]
  12. Jie K., Van Brummelen P., Vermey P., Timmermans P. B., Van Zwieten P. A. Postsynaptic alpha 1- and alpha 2-adrenoceptors in human blood vessels: interactions with exogenous and endogenous catecholamines. Eur J Clin Invest. 1987 Apr;17(2):174–181. doi: 10.1111/j.1365-2362.1987.tb02397.x. [DOI] [PubMed] [Google Scholar]
  13. Kiowski W., Hulthén U. L., Ritz R., Bühler F. R. Alpha 2 adrenoceptor-mediated vasoconstriction of arteries. Clin Pharmacol Ther. 1983 Nov;34(5):565–569. doi: 10.1038/clpt.1983.216. [DOI] [PubMed] [Google Scholar]
  14. Linares O. A., Jacquez J. A., Zech L. A., Smith M. J., Sanfield J. A., Morrow L. A., Rosen S. G., Halter J. B. Norepinephrine metabolism in humans. Kinetic analysis and model. J Clin Invest. 1987 Nov;80(5):1332–1341. doi: 10.1172/JCI113210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Miller T. R., Handelman W. A., Arnold P. E., McDonald K. M., Molinoff P. B., Schrier R. W. Effect of central catecholamine depletion on the osmotic and nonosmotic stimulation of vasopressin (antidiuretic hormone) in the rat. J Clin Invest. 1979 Dec;64(6):1599–1607. doi: 10.1172/JCI109621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nasseri A., Barakeh J. F., Abel P. W., Minneman K. P. Reserpine-induced postjunctional supersensitivity in rat vas deferens and caudal artery without changes in alpha adrenergic receptors. J Pharmacol Exp Ther. 1985 Aug;234(2):350–357. [PubMed] [Google Scholar]
  17. Panza J. A., Epstein S. E., Quyyumi A. A. Circadian variation in vascular tone and its relation to alpha-sympathetic vasoconstrictor activity. N Engl J Med. 1991 Oct 3;325(14):986–990. doi: 10.1056/NEJM199110033251402. [DOI] [PubMed] [Google Scholar]
  18. Prinz P. N., Vitiello M. V., Smallwood R. G., Schoene R. B., Halter J. B. Plasma norepinephrine in normal young and aged men: relationship with sleep. J Gerontol. 1984 Sep;39(5):561–567. doi: 10.1093/geronj/39.5.561. [DOI] [PubMed] [Google Scholar]
  19. Reid I. A. Interactions between ANG II, sympathetic nervous system, and baroreceptor reflexes in regulation of blood pressure. Am J Physiol. 1992 Jun;262(6 Pt 1):E763–E778. doi: 10.1152/ajpendo.1992.262.6.E763. [DOI] [PubMed] [Google Scholar]
  20. Rosen S. G., Linares O. A., Smith M. J., Halter J. B. Downregulation of beta-adrenergic receptor-mediated function during sodium restriction in humans. Am J Physiol. 1989 Oct;257(4 Pt 1):E499–E504. doi: 10.1152/ajpendo.1989.257.4.E499. [DOI] [PubMed] [Google Scholar]
  21. Sekkarie M. A., Egan B. M., Neubig R. R., Supiano M. A. Sensitization of human alpha 1- and alpha 2-adrenergic venous responses by guanadrel sulfate. Clin Pharmacol Ther. 1990 Nov;48(5):537–543. doi: 10.1038/clpt.1990.190. [DOI] [PubMed] [Google Scholar]
  22. Supiano M. A., Hogikyan R. V., Stoltz A. M., Orstan N., Halter J. B. Regulation of venous alpha-adrenergic responses in older humans. Am J Physiol. 1991 Apr;260(4 Pt 1):E599–E607. doi: 10.1152/ajpendo.1991.260.4.E599. [DOI] [PubMed] [Google Scholar]
  23. Supiano M. A., Neubig R. R., Linares O. A., Halter J. B., Rosen S. G. Effects of low-sodium diet on regulation of platelet alpha 2-adrenergic receptors in young and elderly humans. Am J Physiol. 1989 Mar;256(3 Pt 1):E339–E344. doi: 10.1152/ajpendo.1989.256.3.E339. [DOI] [PubMed] [Google Scholar]
  24. Zerbe R. L., Robertson G. L. A comparison of plasma vasopressin measurements with a standard indirect test in the differential diagnosis of polyuria. N Engl J Med. 1981 Dec 24;305(26):1539–1546. doi: 10.1056/NEJM198112243052601. [DOI] [PubMed] [Google Scholar]
  25. van Brummelen P., Jie K., van Zwieten P. A. Alpha-adrenergic receptors in human blood vessels. Br J Clin Pharmacol. 1986;21 (Suppl 1):33S–39S. doi: 10.1111/j.1365-2125.1986.tb02851.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES