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Centrally acting antihypertensive drugs: Re-emergence of sympathetic inhibition in the treatment of hypertension

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Abstract

Central regulation of the sympathetic nervous system plays an important role in the maintenance of blood pressure. In a subset of patients with essential hypertension, sympathetic activation may contribute to the development and maintenance of hypertension. Unlike the first generation of centrally active antihypertensive drugs, the second generation may be superior because of its selectivity to I1-imidazoline receptor and selective binding to the vasomotor center. Lack of a2 effects differentiates moxonidine from clonidine with respect to monoxidine’s superior side-effect profile (little or no sedation or dry mouth). Clinical trials show that moxonidine is as effective as angiotensin-converting enzyme inhibitors (eg, enalapril and captopril), b-blockers (eg, atenolol), calcium-channel blockers (eg, long-acting nifedipine), and diuretics (eg, hydrochlorothiazide) in lowering blood pressure and that it has superior tolerability. Thus, central modulation of the sympathetic nervous system has re-emerged as an exciting target for blood pressure reduction. Given the multiple adverse effects of sympathetic stimulation in various disease processes, including congestive heart failure, moxonidine may be the next therapeutic option for the management of hypertension and the prevention of target organ dysfunction.

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References and Recommended Reading

  1. Sun MK: Central neural organization and control of sympathetic nervous system in mammals. Prog Neurobiol 1995, 47:157–234.

    Article  PubMed  CAS  Google Scholar 

  2. Reis DJ: Neurons and receptors in the rostroventrolateral medulla mediating the antihypertensive actions of drugs acting at imidazoline receptors. J Cardiovasc Pharmacol 1996, 27(suppl 3):S11-S18. This is an excellent review of the central pathways of blood pressure regulation and the possible sites for blood pressure reduction.

    PubMed  CAS  Google Scholar 

  3. Kjeldsen SE, Schork NJ, Leren P, Eide IK: Arterial plasma norepinephrine correlates to blood pressure in middle-aged men with sustained essential hypertension. Am Heart J 1989, 118:775–781.

    Article  PubMed  CAS  Google Scholar 

  4. Qu L, Stuesse SL: Influence of substance P on carotid sinus nerve baro- and chemoreceptor activity in rabbits. Peptides 1990, 11:955–961.

    Article  PubMed  CAS  Google Scholar 

  5. Long CS, Kariya K, Karns L, Simpson PC: Sympathetic activity: modulator of myocardial hypertrophy. J Cardiovasc Pharmacol 1991, 17(suppl 2):S20-S24.

    PubMed  CAS  Google Scholar 

  6. Rosen MR, Danilo P Jr, Robinson RB, et al.: Sympathetic neural and a-adrenergic modulation of arrhythmias. Ann N Y Acad Sci 1988, 533:200–209.

    Article  PubMed  CAS  Google Scholar 

  7. Kaplan JR, Pettersson K, Manuck SB, Olsson G: Role of sympathoadrenal medullary activation in the initiation and progression of atherosclerosis. Circulation 1991, 84(suppl 6):VI23-VI32.

    PubMed  CAS  Google Scholar 

  8. DiBona GF: Sympathetic neural control of the kidney in hypertension. Hypertension 1992,19(suppl I):I28-I35.

    PubMed  CAS  Google Scholar 

  9. DiBona GF, Jones SY, Sawin LL: Renal sympathetic neural mechanisms as intermediate phenotype in spontaneously hypertensive rats. Hypertension 1996, 27:626–630.

    PubMed  CAS  Google Scholar 

  10. Korner PI: Circulatory control and the supercontrollers. J Hypertens 1995, 13:1508–1521.

    Article  PubMed  CAS  Google Scholar 

  11. Zimmerman RS, Frohlich ED: Stress and hypertension. J Hypertens 1990, 8:S103-S107.

    CAS  Google Scholar 

  12. Esler M, Ferrier C, Lamberg G, et al.: Biochemical evidence of sympathetic hyperactivity in human hypertension. Hypertension 1991, 17(suppl III):III29-III35.

    PubMed  CAS  Google Scholar 

  13. Ferrario CM, Averill DB: Do primary dysfunctions in neural control of arterial pressure contribute to hypertension? Hypertension 1991, 18(suppl I):I38-I51.

    PubMed  CAS  Google Scholar 

  14. Julius S, Weder AB: Brain and the regulation of blood pressure: a hemodynamic perspective. Clin Exp Hypertens 1989; 11(suppl 1):1–19.

    Google Scholar 

  15. Mark AL: Regulation of sympathetic nerve activity in mild human hypertension. J Hypertens Suppl 1990, 8:S67-S75.

    Article  PubMed  CAS  Google Scholar 

  16. Ward KD, Sparrow D, Landsberg L, et al.: Influence of insulin, sympathetic nervous system activity, and obesity on blood pressure: the normative aging study. J Hypertens 1996, 14:301–308.

    Article  PubMed  CAS  Google Scholar 

  17. DeQuattro V, Lee DD, Shkhvatasabaya IK, et al.: Primary hypertension, left ventricular mass and function, sympathetic nervous system activity, and therapy. Health Psychol 1988, 7(suppl):165–173.

    Article  PubMed  Google Scholar 

  18. Frank C. Smith S: Stress and the heart: biobehavioral aspects of sudden cardiac death. Psychosomatics 1990, 31:255–264.

    PubMed  CAS  Google Scholar 

  19. Willich SN, Maclure M, Mittleman M, et al.: Sudden cardiac death. Support for a role of triggering in causation. Circulation 1993, 87:1442–1450.

    PubMed  CAS  Google Scholar 

  20. Fedida D, Bouchard RA: Mechanisms for the positive inotropic effect of a1 adrenoceptor stimulation in rat cardiac myocytes. Circ Res 1992, 71:673–688.

    PubMed  CAS  Google Scholar 

  21. Billman GE: Mechanisms responsible for the cardiotoxic effects of cocaine. FASEB J 1990, 4:2469–2475.

    PubMed  CAS  Google Scholar 

  22. Schomig A, Richardt G, Kurz T: Sympatho-adrenergic activation of the ischemic myocardium and its arrhythmogenic impact. Herz 1995, 20:169–186.

    PubMed  CAS  Google Scholar 

  23. Moratinos J, Reverte M: Effects of catecholamines on plasma potassium: the role of a- and b-adrenoceptors. Fundam Clin Pharmacol 1993, 7:143–153.

    Article  PubMed  CAS  Google Scholar 

  24. Opie LH: Sympathetic stimulation of ischemic myocardium: role of plasma free fatty acids and potassium. J Cardiovasc Pharmacol 1988, 12(suppl 1):S31-S38.

    Article  PubMed  CAS  Google Scholar 

  25. Brown MJ, Brown DC, Murphy MB: Hypokalemia from b2-receptor stimulation by circulating epinephrine. N Engl J Med 1983, 309:1414–1419.

    Article  PubMed  CAS  Google Scholar 

  26. Myers MG, Norris JW, Hachniski VC, Sole MJ: Plasma norepinephrine in stroke. Stroke 1981, 12:200–204.

    PubMed  CAS  Google Scholar 

  27. Anfossi G, Trovati M: Role of catecholamines in platelet function: pathophysiological and clinical significance. Eur J Clin Invest 1996, 26:353–370.

    Article  PubMed  CAS  Google Scholar 

  28. Pauletto P, Scannapieco G, Pessina AC: Sympathetic drive and vascular damage in hypertension and atherosclerosis Hypertension 1991, 17(suppl III):III75-III81.

    PubMed  CAS  Google Scholar 

  29. Heusch G: a-Adrenergic mechanisms in myocardial ischemia. Circulation 1990, 81:1–13.

    PubMed  CAS  Google Scholar 

  30. Lee DD, Rigonan K, DeQuattro V: Increased blood pressure and neural tone in the silent ischemia of hypertension: disparate effects of immediate release nifedipine. J Am Coll Cardiol 1993, 22:1438–1445.

    Article  PubMed  CAS  Google Scholar 

  31. Yurenev AP, DeQuattro V, Dubov PB, et al.: Silent myocardial ischemia in patients with essential hypertension. Am J Hypertens 1992, 5:169–174.

    Google Scholar 

  32. Ernsberger P, Westbrooks KL, Christen MO, Schaefer SG: A second generation of centrally acting antihypertensive agents act on putative I1-imidazoline receptors. J Cardiovasc Pharmacol 1992, 20(suppl 4):S1-S10. This is a comprehensive review of the molecular and cellular effects of newer centrally acting antihypertensive drugs, including moxonidine.

    CAS  Google Scholar 

  33. Ernsberger P, Collins LA, Graves ME, et al.: Imidazoline I1 receptors in the ventrolateral medulla and their role in cardiorespiratory control. In In Ventral Brainstem Mechanisms and Control Functions. Edited by Trouth O, Millis R, Kiwell-Schone H, Schlafke M. New York: Marcel Dekker; 1995:319–358.

    Google Scholar 

  34. Ernsberger P, Graves ME, Graff LM, et al.: I1-Imidazoline receptors: definition, characterization, distribution and transmembrane signaling. Ann N Y Acad Sci 1995, 763:22–42.

    Article  PubMed  CAS  Google Scholar 

  35. Frei M, Kuster L, Gardosch-von Krosigk P-P, et al.: Moxonidine and hydrochlorothiazide in combination: a synergistic antihypertensive effect. J Cardiovasc Pharmacol 1994, 24 (suppl 1):S25-S26.

    PubMed  CAS  Google Scholar 

  36. Kuppers H, Jager B, Luszick J, et al.: Placebo-controlled comparison of the efficacy and tolerability of once-daily moxonidine and enalapril in mild-to-moderate essential hypertension. J Hypertens 1997, 15:93–97. This major study compares the efficacy of moxonidine with that of enalapril. Both drugs were equally effective in lowering blood pressure and had very good tolerability. AU: Changes to annotation ok?

    Article  PubMed  CAS  Google Scholar 

  37. Lotti G, Gianrossi R: Moxonidin vs captopril bei leichter bis mittelschwerer hypertonie: doppelblindstudie zur wirksamkeit and vertraglichkeit. Fortschr Med 1993, 111:429–432.

    PubMed  CAS  Google Scholar 

  38. Kraft K, Vetter H: Twenty-four-hour blood pressure profiles in patients with mild-to-moderate hypertension: moxonidine versus captopril. J Cardiovasc Pharmacol 1994, 24(suppl 1):S29-S35.

    PubMed  CAS  Google Scholar 

  39. Prichard BNC: Clinical experience with moxonidine. Cardiovasc Drugs Ther 1994, 8(suppl 1):49–58. This is a comprehensive review of the effects of moxonidine, although it does not include the newer data or results in patients with heart failure.

    Article  PubMed  Google Scholar 

  40. Wolf R: The treatment of hypertensive patients with a calcium antagonist or moxonidine: a comparison. J Cardiovasc Pharmacol 1992, 20(suppl 4):S42-S44.

    Article  Google Scholar 

  41. Planitz V: Crossover comparison of moxonidine and clonidine in mild-to-moderate hypertension. Eur J Pharmacol 1984, 27:147–152.

    Article  CAS  Google Scholar 

  42. Planitz V, Hoffmann K, Stenzel W: A double-blind crossover trial of moxonidine hydrochloride monohydrate (BF5895) and clonidine hydrochloride in hypertensive patients. Naunyn Schmeidebergs Arch Pharmacol 1984, 325(suppl):84–88.

    Google Scholar 

  43. Schwarz VW, Kandziora J: Langzeiterfahrungen mit moxonidin einem neuen antihypertensivum. Forschr Med 1990, 108:64–70.

    Google Scholar 

  44. Trieb G, Jager B, Hughes PR, et al.: Long-term evaluation of the antihypertensive efficacy and tolerability of the orally-acting imidazoline I1 receptor agonist moxonidine in patients with mild to moderate essential hypertension. Eur J Clin Res 1995, 7:227–240.

    Google Scholar 

  45. Schrader J, Schoel G, Gundlach K, et al.: Antihypertensive wirkdauer und morgendlicher blutdruckanstieg unter moxonidine in der ambulanten 24-stunden-blutdruckmessung. Nieren Hochdruckkrankh 1992, 21:531–533.

    Google Scholar 

  46. Levy D, Garrison RJ, Savage DD, et al.: Prognostic implication of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990, 322:1561–1566.

    Article  PubMed  CAS  Google Scholar 

  47. Pfeffer MA, Pfeffer JM: Reversing cardiac hypertrophy in hypertension. N Engl J Med 1990, 322:1388–1389.

    PubMed  CAS  Google Scholar 

  48. Eichstadt H, Richter W, Bader M, et al.: Demonstration of hypertrophy regression with magnetic resonance tomography under the new adrenergic inhibitor moxonidine. Cardiovasc Drugs Ther 1989, 3(suppl 2):583–587.

    Google Scholar 

  49. Motz W, Vogt M, Scheler S, Strauer BE: Hypertensive coronary microcirculation effects of the imidazoline-receptor-agonist moxonidine. Cardiovasc Risk Fact 1995, 5(suppl 1):28–32.

    Google Scholar 

  50. Feuring M, Cassal D, Stewenov D, et al.: Safety of moxonidine in patients with mild-to-moderate hypertension and chronic pulmonary disease. Hospitalis 1996, 67:A553.

    Google Scholar 

  51. Kirch W, Planitz V: Klinische aspekte der therapie mit einem zentral wirksamen alpha2-adrenozeptor-agonisten bei patienten mit arterieller hypertonie. CorVas 1991, 5:1–12.

    Google Scholar 

  52. Ongyert D, Dotzer F: Wirksamkeit und vergraglichkeit von moxonidin. Z Allg Med 1993, 69:S56-S60.

    Google Scholar 

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  1. Division of Cardiology, University of Texas Medical School, 6431 Fannin Street, MSB 6.039, 77030, Houston, Texas, USA

    Claude R. Benedict MD, DPhil

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Benedict, C.R. Centrally acting antihypertensive drugs: Re-emergence of sympathetic inhibition in the treatment of hypertension. Current Science Inc 1, 305–312 (1999). https://doi.org/10.1007/s11906-999-0038-1

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