Skip to main content
SpringerLink
Log in

The effect of captopril and propranolol on the responses to posture and isometric exercise in patients with essential hypertension

  • Originals
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Summary

The effects of captopril and propranolol on blood pressure, heart rate and plasma noradrenaline, renin and aldosterone, and on the responses to changes in posture and to isometric exercise were measured in patients with essential hypertension. During placebo administration blood pressure, heart rate and plasma noradrenaline rose on standing and during isometric exercise. The rise in diastolic blood pressure during isometric exercise correlated significantly with the rise in plasma noradrenaline. During captopril treatment blood pressure was significantly lower than during placebo administration when the patients were lying, standing or sitting, but the reduction during isometric exercise was not significant. Plasma renin increased, but heart rate, plasma noradrenaline and plasma aldosterone remained unchanged. The acute changes in blood pressure, heart rate and plasma noradrenaline produced by standing and isometric exercise during captopril treatment were similar to those during placebo administration. During propranolol treatment diastolic blood pressure was significantly lower than during placebo administration when the patients were lying, standing or sitting and during isometric exercise. Heart rate also fell. Plasma noradrenaline during standing, sitting and isometric exercise was significantly greater than during placebo administration. The changes in plasma noradrenaline measured during propranolol treatment with the patients supine were negatively correlated with noradrenaline values obtained during placebo administration: plasma noradrenaline fell in patients with higher, and increased in those with lower, initial concentrations. The expected acute increase in heart rate on standing and during isometric exercise was blunted by propranolol, but the changes in blood pressure and plasma noradrenaline were unaffected. We conclude that in essential hypertension noradrenaline is involved in the pressor response to isometric exercise. Angiotensin converting enzyme inhibition by captopril did not interfere with the responses of the sympathetic nervous system to postural changes and isometric exercise. During propranolol treatment there was no evidence that reduced sympathetic activity was involved in the hypotensive response.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ferrario CM, Gildenberg PL, McCubbin JW (1972) Cardiovascular effects of angiotensin mediated by the central nervous system. Circ Res 30: 257–262

    Google Scholar 

  2. Severs WB, Daniels-Severs AE (1973) Effects of angiotensin on the central nervous system. Pharmacol Rev 25: 415–449

    Google Scholar 

  3. Roth RH (1972) Action of angiotensin on adrenergic nerve endings: Enhancement of norepinephrine biosynthesis. Fed Proc 31: 1358–1364

    Google Scholar 

  4. Peach MJ (1971) Adrenal medullary stimulation induced by angiotensin I, angiotensin II, and analogues. Circ Res 28/29 [Suppl II]: 107–117

    Google Scholar 

  5. Zimmerman BG (1978) Actions of angiotensin on adrenergic nerve endings. Fed Proc 37: 199–202

    Google Scholar 

  6. Hughes J, Roth RH (1971) Evidence that angiotensin enhances transmitter release during sympathetic nerve stimulation. Br J Pharmacol 41: 239–255

    Google Scholar 

  7. Khairallah PA, Davila D, Papanicolaou N, Glende NM, Meyer P (1971) Effects of angiotensin infusion on catecholamine uptake and reactivity in blood vessels. Circ Res 28/29 [Suppl II]: II-96–II-106

    Google Scholar 

  8. Palaic D, Khairallah PA (1967) Inhibition of noradrenaline uptake by angiotensin. J Pharm Pharmacol 19: 396–397

    Google Scholar 

  9. Kondo K, Manku MS, Horrobin DF, Boucher R, Genest J (1977) Potentiation of pressor effects of noradrenaline and potassium ions in the rat mesenteric arteries by physiological concentrations of angiotensin II: effects of prostaglandin E2 and cortisol. Clin Sci Mol Med 53: 233–239

    Google Scholar 

  10. Lewis PJ, Haeusler G (1975) Reduction in sympathetic nervous activity as a mechanism for hypotensive effect of propranolol. Nature 256: 440

    Google Scholar 

  11. Lewis P (1976) The essential action of propranolol in hypertension. Am J Med 60: 837–852

    Google Scholar 

  12. Langer SZ, Cavero I, Massingham R (1980) Recent developments in noradrenergic neurotransmission and its relevance to the mechanism of action of certain antihypertensive agents. Hypertension 2: 372–382

    Google Scholar 

  13. Rhah KH, Gierlichs HW, Planz G, Planz R, Schols M, Stephany W (1978) Studies on the effects of propranolol on plasma catecholamine levels in patients with essential hypertension. Eur J Clin Invest 8: 143–148

    Google Scholar 

  14. Jones DH, Daniel J, Hamilton CA, Reid JL (1980) Plasma noradrenaline concentration in essential hypertension during long-term β-adrenoceptor blockade with oxprenolol. Br J Clin Pharmacol 9: 27–31

    Google Scholar 

  15. McGrath BP, Beilin LJ, Schofield T, Benedict CR, Barker NP, Cooper R (1979) Home blood pressure monitoring and changes in plasma catecholamines during once or twice daily treatment with atenolol in patients with mild hypertension. Aust N Z J Med 9: 374–381

    Google Scholar 

  16. Brecht HM, Banthien F, Schoeppe W (1976) Decrease in plasma noradrenaline levels following long term treatment with pindolol in patients with essential hypertension. Klin Wochenschr 54: 1095–1105

    Google Scholar 

  17. Wilcox CS, Lewis PS, Peart WS, Sever PS, Osikowska BA, Suddle SAJ, Bluhm MM, Veall N, Lancaster R (1981) Renal function, body fluid volumes, renin, aldosterone and noradrenaline during treatment of hypertension with pindolol. J Cardiovasc Pharmacol 3: 598–611

    Google Scholar 

  18. Watson RDS, Eriksson B-M, Hamilton CA, Reid JL, Stallard TJ, Littler WA (1980) Effects of chronic beta-adrenoreceptor antagonism on plasma catecholamines and blood pressure in hypertension. J Cardiovasc Pharmacol 2: 725–738

    Google Scholar 

  19. Sealey JE, Gerten-Banes J, Laragh JH (1972) The renin system: Variations in man measured by radio-immunoassay or bio-assay. Kidney Int 1: 240–253

    Google Scholar 

  20. Henry DP, Starman BJ, Johnson DG, Williams RH (1975) A sensitive radioenzymatic assay for norepinephrine in tissues and plasma. Life Sci 16: 375–384

    Google Scholar 

  21. Martin CE, Shaver JA, Leon DF, Thompson ME, Reddy PS, Leonard JJ (1974) Autonomic mechanisms in haemodynamic responses to isometric exercise. J Cin Invest 54: 104–115

    Google Scholar 

  22. Hume L, Ewing DJ, Campbell IW, Reuben SR, Clarke BF (1979) Heart rate response to sustained hand grip: Comparison of the effects of cardiac autonomic blockade and diabetic autonomic neuropathy. Clin Sci 56: 287–291

    Google Scholar 

  23. Laird WP, Fixler DE, Huffines FD (1979) Cardiovascular response to isometric exercise in normal adolescents. Circulation 59: 651–654

    Google Scholar 

  24. Ewing DJ, Irving JB, Kerr F, Kirby BJ (1973) Static exercise in untreated systemic hypertension. Br Heart J 35: 413–421

    Google Scholar 

  25. De Leeuw PW, Wester A, Falke HE, Stienstra R, Birkenhager WH (1978) Noradrenaline responses to haemodynamic stimuli. In: Birkenhager WH, Falke HE (eds) Circulating catecholamines and blood pressure (Proc. Symp. Rotterdam) Burge Scientific Publications, Utrecht, p 58–63

    Google Scholar 

  26. Kozlowski S, Brzezinska Z, Nazar K, Kowalski W, Franczyk M (1973) Plasma catecholamines during sustained isometric exercise. Clin Sci Mol Med 45: 723–731

    Google Scholar 

  27. Lake CR, Ziegler MG, Kopin IJ (1976) Use of plasma norepinephrine for evaluation of sympathetic neuronal function in man. Life Sci 18: 1315–1326

    Google Scholar 

  28. Christensen NJ, Galbo H, Hansen JF, Hesse B, Richter EA, Trap-Jensen J (1979) Catecholamines and exercise. Diabetes 28 [Suppl I]: 58–62

    Google Scholar 

  29. Vecht RJ, Graham GWS, Sever PS (1978) Plasma noradrenaline concentrations during isometric exercise. Br Heart J 40: 1216–1220

    Google Scholar 

  30. McAllister RG (1979) Effect of adrenergic receptor blockade on the responses to isometric handgrip: Studies in normal and hypertensive subjects. J Cardiovasc Pharmacol 1: 253–263

    Google Scholar 

  31. Peach MJ, Bumpus FM, Khairallah PA (1971) Release of adrenal catecholamines by angiotensin I. J Pharmacol Exp Ther 176: 366–376

    Google Scholar 

  32. Muiesan G, Alicandri CL, Agabiti-Rosei E, Fariello R, Beschi M, Boni E, Castellano M, Moniti E, Muiesan L, Romanelli G, Zanielli A (1982) Angiotensin converting enzyme inhibition, catecholamines and hemodynamics in essential hypertension. Am J Cardiol 49: 1420–1424

    Google Scholar 

  33. Manhem P, Bramnert M, Hulthen UL, Hokfelt B (1981) The effect of captopril on catecholamines, renin activity, angiotensin II and aldosterone in plasma during physical exercise in hypertensive patients. Eur J Clin Invest 11: 389–395

    Google Scholar 

  34. Campbell BC, Shepherd AN, Reid JL (1982) Effects of the angiotensin converting enzyme inhibitor, captopril, in essential hypertension. Br J Clin Pharmacol 13: 213–217

    Google Scholar 

  35. Morganti A, Pickering TG, Lopez-Ovejero J, Laragh JH (1979) Humoral effects of the oral converting enzyme inhibitor SQ 14.225 in hypertensive patients in supine and tilted postion. Clin Sci 57: 149s-152s

    Google Scholar 

  36. Beretta-Piccoli C, Weidmann P, Keusch G, Gluck Z, Grimm M, Meier A, Minder I (1980) Responsiveness of circulating catecholamines, renin and aldosterone to angiotensin II. Min Electrol Metab 4: 137–148

    Google Scholar 

  37. Vlachakis ND, Ribeiro AB, Krakoff LR (1978) Effect of saralasin upon plasma catecholamines in hypertensive patients. Am Heart J 95: 78–80

    Google Scholar 

  38. Squibb research investigators brochure (1976) Effect of SQ 14.225 on sympathetic, ganglionic, neuronal and receptor function. Reference 52, Squibb International Report 10/29/76

  39. Clough DP, Collis MG, Conway J, Hatton R, Keddie J (1982) Interaction of angiotensin converting enzyme inhibitors with the function of the sympathetic nervous system. Am J Cardiol 49: 1410–1414

    Google Scholar 

  40. Planz G, Planz R (1981) Dissociation between duration of plasma catecholamines and blood pressure responses to beta-adrenergic blockade in normotensive subjects during physical exercise. Eur J Clin Pharmacol 19: 83–88

    Google Scholar 

  41. Guyton AC, Coleman TG, Cowley AW, Manning RD, Norman RA, Ferguson JD (1974) A systems analysis approach to understanding long-range arterial blood pressure control and hypertension. Circ Res 35: 159–176

    Google Scholar 

  42. Guyton AC, Coleman TG, Cowley AW, Scheel KW, Manning RD, Norman RA (1972) Overriding dominance of the kidneys in long-term regulation and in hypertension. Am J Med 52: 584–594

    Google Scholar 

  43. Cryer PE, Rizza RA, Haymond MW, Gerich JE (1980) Epinephrine and norepinephrine are cleared through beta-adrenergic, but not alpha-adrenergic, mechanisms in man. Metabolism 29: 1114–1118

    Google Scholar 

  44. von Euler US, Lishajko F (1968) Inhibitory action of adrenergic blocking agents on reuptake and net uptake on noradrenaline in nerve granules. Acta Physiol Scand 74: 501–506

    Google Scholar 

  45. Eisenfeld AJ, Axelrod J, Krakoff L (1967) Inhibition of the extraneuronal accumulation and metabolism of norepinephrine by adrenergic blocking agents. J Pharmacol Exp Ther 156: 107–113

    Google Scholar 

  46. Eisenfeld AJ, Landsberg L, Axelrod J (1967) Effect of drugs on the accumulation and metabolism of extraneuronal norepinephrine in the rat heart. J Pharmacol Exp Ther 158: 378–385

    Google Scholar 

  47. Falch DK, Odegaard AE, Norman N (1979) Decreased renal plasma flow during propranolol treatment in essential hypertension. Acta Med Scand 205: 91–95

    Google Scholar 

  48. Nies AS, Evans GH, Shand DG (1973) The haemodynamic effects of beta-adrenergic blockade on the flow-dependent hepatic clearance of propranolol. J Pharmacol Exp Ther 184: 716–720

    Google Scholar 

  49. Cousineau D, De Champlain J, Lapointe L (1978) Circulating catecholamines and systolic time intervals in labile and sustained hypertension. Clin Sci 55: 65s-68s

    Google Scholar 

  50. Esler M, Zweifler A, Randall O, Julius S, Dequattro V (1977) Agreement among three different indices of sympathetic nervous system activity in essential hypertension. Mayo Clin Proc 52: 379–382

    Google Scholar 

  51. Brown MJ, Jenner DA, Allison DJ, Dollery CT (1981) Variations in individual organ release of noradrenaline measured by an improved radioenzymatic technique; limitations of peripheral venous measurements in the assessment of sympathetic nervous activity. Clin Sci 61: 585–590

    Google Scholar 

  52. Wallin BG, Sundlof G, Eriksson BM, Dominiak P, Grobecker H, Lindblad LE (1981) Plasma noradrenaline correlates to sympathetic muscle nerve activity in normotensive man. Acta Physiol Scand 111: 69–73

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Unit, Department of Nephrology and Department of Clinical Chemistry, The London Hospital, London, UK

    M. J. Vandenburg, J. M. P. Holly, F. J. Goodwin, V. L. Sharman & F. P. Marsh

Authors
  1. M. J. Vandenburg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. M. P. Holly
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. J. Goodwin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V. L. Sharman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. F. P. Marsh
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vandenburg, M.J., Holly, J.M.P., Goodwin, F.J. et al. The effect of captopril and propranolol on the responses to posture and isometric exercise in patients with essential hypertension. Eur J Clin Pharmacol 25, 721–728 (1983). https://doi.org/10.1007/BF00542509

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00542509

Key words

Search

Navigation