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Acute and chronic hemodynamic effects of drugs with different actions on adrenergic receptors: A comparison between alpha blockers and different types of beta blockers with and without vasodilating effect

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Summary

The regulation of vascular resistance, cardiac out-put, and thus blood pressure can be influenced by antihypertensive drugs acting at central and peripheral adrenergic receptors. The results presented here are from acute or chronic studies in 205 patients with mild or moderately severe essential hypertension: beta blockers (N = 101); alpha blockers (N = 36); a separate alpha- + beta-blocker combination or the combination agent labetalol (N = 37); prizidilol, a beta-blocker/vasodilator (N = 14); and dilevalol, a beta blocker/ beta2-stimulator (N = 17). Beta blockers without strong intrinsic sympathomimetic activity reduce heart rate and cardiac output immediately, but due to a reflex increase in total peripheral resistance index, blood pressure is unchanged or only slightly reduced. During chronic use, total peripheral resistance drops towards pretreatment level and pressure falls. Beta blockers with strong intrinsic sympathomimetic activity do not reduce heart rate or cardiac output at rest when sympathetic tone is low. During exercise, heart rate and cardiac output are reduced, but less than with conventional beta blockers, and resistance is unchanged or slightly reduced. An acute and chronic reduction in blood pressure can be produced by alpha-adrenergic receptor blockers (prazosin, doxazosin, trimazosin), and in these cases the fall occurs via a reduction in total peripheral resistance index without reflex tachycardia. These drugs tend to increase exercise stroke volume and cardiac output during chronic treatment. Free combinations of beta and alpha blockers or the use of the fixed combination drug, labetalol, induce marked reductions in blood pressure at rest and during exercise, mainly through a reduction in total peripheral resistance index. During chronic treatment, exercise stroke volume and cardiac output are well maintained. In acute studies with dilevalol, systolic blood pressure, diastolic blood pressure, and mean arterial pressure were reduced (p < 0.001) within 1 hour in 17 males with essential hypertension (WHO stage I) who received 200–400 mg oral dilevalol. The reduction in MAP was around 16–17% and was associated with an immediate fall in the total peripheral resistance index of the same magnitude (14%, p < 0.001) after 1 hour at rest. There were no significant changes in heart rate or cardiac index. In our chronic study (6 to 9 months), the beta-blocking effect of dilevalol was most prominent during exercise, with a 22% reduction in heart rate. This was partly compensated for by an 8% increase in stroke volume, and so the reduction in cardiac index was less pronounced than heart rate. Total peripheral resistance index was practically unchanged. In our study on beta blockers, chronic vasodilation was better maintained by added alpha1 blockade than by beta2-stimulation.

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References

  1. Lund-Johansen P. The hemodynamics of essential hypertension. In: Robertson JIS, ed.Clinical aspects of essential hypertension. (Handbook of Hypertension, Vol. I). Amsterdam: Elsevier, 1983:151–173.

    Google Scholar 

  2. Conway J. Hemodynamic aspects of essential hypertension in humans.Physiol Rev 1984;64:617–659.

    PubMed  CAS  Google Scholar 

  3. Mulvany MJ. The structure of the resistance vasculature in essential hypertension.J Hypertens 1987;5:129–136.

    Article  PubMed  CAS  Google Scholar 

  4. Lund-Johansen P. Hemodynamic effects of antihypertensive agents. In: Doyle E, ed.Clinical pharmacology of antihypertensive drugs. (Handbook of Hypertension, Vol. V). Amsterdam: Elsevier, 1988:41–72.

    Google Scholar 

  5. Lund-Johansen P. Central hemodynamic effects of beta-blockers in hypertension. A comparison between atenolol, metoprolol,timolol, penbutolol, alprenolol, pindolol and bunitrolol.Eur Heart J 1983;(Suppl. 4):1–12.

  6. Lund-Johansen P, Omvik P, Haugland H. Acute and chronic haemodynamic effects of doxazosin in hypertension at rest and during exercise.Br J Clin Pharmacol 1986;21:45S-54S.

    PubMed  Google Scholar 

  7. Lund-Johansen P. Short- and long-term (six-years) hemodynamic effects of labetalol in essential hypertension.Am J Med 1983;75:24–31 (symposium issue).

    Article  PubMed  CAS  Google Scholar 

  8. Lund-Johansen P, Omvik P, Haugland H. Initial haemodynamic effects of ICI 141 292, a cardioselective beta-blocker with ISA at rest and during exercise in patients with essential hypertension.Acta Med Scand 1984;(Suppl. 693): 121–125.

  9. Omvik P, Lund-Johansen P. Acute hemodynamic effects of labetalol in severe hypertension.J Cardiovasc Pharmacol 1982;4:915–920.

    Article  PubMed  CAS  Google Scholar 

  10. Man in’t Veld A, Meiracker AH. Effects of antihypertensive drugs on cardiovascular hemodynamics. In: Laragh JH, Brenner BN, eds.Hypertension: Pathophysiology, diagnosis and management. New York: Raven Press, 1990: 2117–2130.

    Google Scholar 

  11. Zwieten van PA. Alpha-adrenoceptor-blocking agents in the treatment of hypertension. In: Laragh JH, Brenner BN, eds.Hypertension: Pathophysiology, diagnosis and management. New York: Raven Press, 1990:2233–2249.

    Google Scholar 

  12. Omvik P, Lund-Johansen P. Review of central hemodynamic effects of alpha-blockers and their use in hypertension.Br J Clin Pract 1987;41(Suppl. 54):15–21.

    Google Scholar 

  13. Lund-Johansen P. Hemodynamic changes at rest and during exercise in long-term prazosin therapy of essential hypertension. In: Cotton DWK, ed.Prazosin—Evaluation of a new antihypertensive agent. Amsterdam: Excerpta Medica. 1984:43–53.

    Google Scholar 

  14. Brogden RN, Heel RC, Speight TM, et al. Labetalol: A review of its pharmacology and therapeutic use in hypertension.Drugs 1978;15:251–270.

    Article  PubMed  CAS  Google Scholar 

  15. Joekes AM, Thompson FD. Acute haemodynamic effects of labetalol and its subsequent use as an oral hypotensive agent.Br J Clin Pharmacol 1976;3(Suppl. 3):789–793.

    PubMed  CAS  Google Scholar 

  16. Koch G. Hemodynamic effects of combined alpha- and beta-adrenoceptor blockade after intravenous labetalol in hypertensive patients at rest and during exercise.Br J Clin Pharmacol 1976;3(Suppl. 3):725–728.

    PubMed  CAS  Google Scholar 

  17. Agabiti-Rosei E, Alicandri CL, Beschi M, et al. The acute and chronic hypotensive effect of labetalol and the relationship with pre-treatment plasma noradrenaline levels.Br J Clin Pharmacol 1982;13:87S-92S.

    PubMed  CAS  Google Scholar 

  18. Fagard R, Lijnen P, Amery A. Response of the systemic and pulmonary circulation to labetalol at rest and during exercise.Br J Clin Pharmacol 1982;13(Suppl. 1):13S-17S.

    PubMed  CAS  Google Scholar 

  19. Mehta J, Cohn JN. Hemodynamic effects of labetalol, an alpha- and beta-adrenergic blocking agent in hypertensive subjects.Circulation 1977;55:370–375.

    PubMed  CAS  Google Scholar 

  20. Fagard R, Amery A, Reybrouck T, et al. Response of the systemic and pulmonary circulation to alpha- and beta-receptor blockade (labetalol) at rest and during exercise in hypertensive patients.Circulation 1979;60:1214–1219.

    PubMed  CAS  Google Scholar 

  21. Edwards RC, Raftery EB. Haemodynamic effects of long-term oral labetalol.Br J Clin Pharmacol 1976;3(Suppl. 3):733–736.

    PubMed  CAS  Google Scholar 

  22. Svendsen TJ, Rasmussen S, Hartling OJ, et al. Acute and long-term effects of labetalol on systemic and pulmonary hemodynamics in hypertensive patients.Eur J Clin Pharmacol 1980;17:5–11.

    Article  PubMed  CAS  Google Scholar 

  23. Kock G. Haemodynamic adaptation at rest and during exercise to long term antihypertensive treatment with combined alpha- and beta-adrenoceptor blockade by labetalol.Br Heart J 1979;41:192–198.

    Article  Google Scholar 

  24. Lund-Johansen P, Bakke OM. Haemodynamic effects and plasma concentration of labetalol during long-term treatment of essential hypertension.Br J Clin Pharmacol 1979;7:169–174.

    PubMed  CAS  Google Scholar 

  25. Lund-Johansen P. Pharmacology of combined alpha-beta-blockade II. Haemodynamic effects of labetalol.Drugs 1984;29(Suppl. 2):35–50.

    Article  Google Scholar 

  26. Lund-Johansen P, Omvik P. Prizidilol in essential hypertension: Long-term effects on plasma volume, extracellular fluid volume, and central hemodynamics at rest and during exercise.J Cardiovasc Pharmacol 1982;4:1012–1017.

    Article  PubMed  CAS  Google Scholar 

  27. Baum TH, Sybertz EJ. Antihypertensive actions of an isomer of labetalol and other vasodilator-beta-adrenoceptor blockers.Fed Proc 1983;42:176–181.

    PubMed  CAS  Google Scholar 

  28. Brittain RT, Drew GM, Levy GP. The alpha- and beta-adrenoceptor blocking potencies of labetalol and its individual stereoisomers in anaesthetized dogs and in isolated tissues.Br J Pharmacol 1982;77:105–114.

    PubMed  CAS  Google Scholar 

  29. Sybertz EJ, Sabin CS, Pula KK, et al. Alpha and beta adrenoceptor blocking properties of labetalol and its R,R-isomer, SCH 19927.J Pharmacol Exp Ther 1981;218:435–443.

    PubMed  CAS  Google Scholar 

  30. Wikstrand J, Warnold I, Olsson G, et al. Primary prevention with metoprolol in patients with hypertension. Mortality results from the MAPHY study.JAMA 1988;259:1976–1982.

    Article  PubMed  CAS  Google Scholar 

  31. Lundborg P, Aström H, Bengtsson C. Effect of beta-adrenoceptor blockade on exercise performance and metabolism.Clin Sci 1981;61:299–305.

    PubMed  CAS  Google Scholar 

  32. Matsunaga K, Nakamura K, Ueda M. Intrinsic beta-sympathomimetic activity of dilevalol, R,R-isomer of labetalol.J Pharmacobiodyn 1985;8:785–787.

    PubMed  CAS  Google Scholar 

  33. Tsukiyama H, Otsuka K, Takasaki I, et al. Hemodynamic effects of N-696 and dilevalol, new beta-blocking agents with vasodilatory properties, and urapidil and doxazosin, alpha-blocking agents in essential hypertension. Third European Meeting on Hypertension, Milan, abstract 1987.

  34. Strom JA, Vidt DG, Bugni W, et al. Mechanism of antihypertensive action of dilevalol compared with that of “cardio-selective” beta-blocking agents.Am J Cardiol 1989;63: 251–331.

    Article  Google Scholar 

  35. Bugni WJ, Ayers CW, Ashby R, et al. Effects of dilevalol on rest and supine exercise hemodynamics in mild to moderate systemic hypertension.Am J Cardiol 1989;63:452–456.

    Article  PubMed  CAS  Google Scholar 

  36. Chrisp P, Goa KL. Dilevalol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in hypertension.Drugs 1990;39(Suppl. 2):234–263.

    Article  PubMed  CAS  Google Scholar 

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  1. Medical Department, Haukeland Hospital, University of Bergen, Bergen, Norway

    Per Lund-Johansen & Per Omvik

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  1. Per Lund-Johansen
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  2. Per Omvik
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Lund-Johansen, P., Omvik, P. Acute and chronic hemodynamic effects of drugs with different actions on adrenergic receptors: A comparison between alpha blockers and different types of beta blockers with and without vasodilating effect. Cardiovasc Drug Ther 5, 605–615 (1991). https://doi.org/10.1007/BF03029729

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