583
Letters to the Editor Letters to the Editor will be published, if suitable, as space permits. They should not exceed 1,000 words (typed double-spaced) in length and may be subject to editing or abridgment.
Epinephrine and the Genesis of Hypertension To the Editor. I read with interest in the January 1992 issue of Hypertension the Brief Review by John S. Floras1 entitled "Epinephrine and the Genesis of Hypertension." As a matter of fact he himself puts it wisely: "the epinephrine hypothesis, itself, remains unproven." May I add that there are other facts that disprove this hypothesis, inter allia, the absence of hypertension in smokers, who have no other risk factors.2-3 We know that smoking cigarettes increases the amount of catecholamines in the blood plasma substantially.4-7 Smoking a single cigarette increases the blood pressure, but as stated above, smokers have a lower blood pressure when compared with their nonsmoking counterparts. Also patients who are suffering from pheochromocytoma have increased blood pressure. They have, of course, a very large increase of catecholamines in their blood plasma, but after a successful operation, if they have not developed irreversible changes in their kidneys, their blood pressure returns to its previous level.8 These two instances alone disprove the epinephrine hypothesis of the genesis of hypertension. Otto Frankl Department of Medicine (retired) Chaim Sheba Medical Center Tel-Hashomer Sadder School of Medicine (retired) University of Tel-Aviv Israel
References 1. Floras JS: Epinephrine and the genesis of hypertension. Hypertension 1992;20:l-18 2. Green MS, Jucha E, Luz Y: Blood pressure in smokers and nonsmokers: Epidemiologic findings. Am Heart J 1986;lll:932-94O 3. Benowitz NL, Sharp DS: Inverse relation between serum cotinine concentration and blood pressure in cigarette smokers. Circulation 1989;80:1309-1312 4. Benowitz NL: Clinical pharmacology of nicotine. Anna Rev Med 1986^7:21-32 5. Benowitz NL: Pharmacologic aspects of cigarette smoking and nicotine addiction. N EnglJ Med 1988^19:1318-1330 6. Cryer PE, Haymond MW, Santiago JV, Shah SO: Norepinephrine and epinephrine release and adrenergic mediation on smokingassociated hemodynamic and metabolic events. N EnglJ Med 1976; 295:573-577 7. Siess W, Lorenz R, Roth R, Weber PC: Plasma catecholamines, platelets aggregation and associated thromboxane formation after physical exercise, smoking, or norepinephrine infusion. Circulation 1982;66:45-48 8. Christensen JN: Catecholamines and essential hypertension, (editorial review) Scand J Can Lab Invest 1982;42L21 1-215 The following is in response: To the Editor.
Dr. Frankl raises two interesting issues. Neither directly refutes the epinephrine hypothesis as developed in the review.
An acute bout of heavy smoking will cause marked increases in blood pressure and heart rate in habitual smokers,1 and ambulatory blood pressures are increased by smoking.1-2 These pressor effects of smoking may not be appreciated if blood pressure is recorded during abstinence.1 The two population studies cited by Dr. Frankl do not constitute a rigorous test of the epinephrine hypothesis since they were descriptive rather than mechanistic in design. Pheochromocytomata are interesting in that a neurogenic component to the higher blood pressure of patients harboring such tumors can be unmasked by the clonidine suppression test.3 Epinephrine could act both directly and as a cotransmitter on prejunctional ft adrenergic receptors to increase noradrenergic release and augment neurogenic vasoconstriction in such patients. Approximately 25% of patients exhibit primary hypertension after tumor removal/ Since patients do not ordinarily present with detailed documentation of their blood pressure previous to the development of pheochromocytomata, it cannot be assumed that blood pressure does return to its "previous level" in the remaining 75%. One of the key concepts developed in my review5 is that ft adrenergic receptor-mediated facilitation of norepinephrine release appears to occur only during a period of critical sensitivity to epinephrine. A second point I emphasized is that expression of high blood pressure by this mechanism may be restricted to a specific subset of individuals with a genetic predisposition to primary hypertension. As was concluded, the most compelling interventional tests of the epinephrine hypothesis would require identification of such individuals at the earliest and mildest stage of their disease, well before the development of clinically established hypertension. Neither the broadly based population study of smoking and blood pressure by Green and his colleagues6 (from which 11-15% of subjects screened were excluded because of previously documented hypertension) nor the anecdotal remark on pheochromocytoma cited by Dr. Frankl fulfill these criteria. John S. Fioraii Division of Cardiology Department of Medicine Toronto General Hospital Toronto, Canada
References 1. Groppelli A, Giorgi DMA, Omboni S, Parati G, Mancia G: Persistent blood pressure increase induced by heavy smoking. J Hypertais 1992;10:495-499 2. Schnall PL, Schwartz JE, Landsbergis PA, Warren K, Pickering TG: Relation between job strain, alcohol and ambulatory blood pressure. Hypertension 1992; 19:488-494 3. Bravo EL, Tarazi RC, Fouad FM, Vidt DG, Gifford RW: Clonidinesuppression test. N EnglJ Med 1981^05:623-626 4. Manger WM, Gifford RW: Pheochromocytoma, in Laragh JH, Brenner BM (eds): Hypertension: Pathophysiology, Diagnosis, and Management. New York, Raven Press, Publishers, 1990 5. Floras JS: Epinephrine and the genesis of hypertension. Hypertension 1992;19:1-18 6. Green MS, Jucha E, Luz Y: Blood pressure in smokers and nonsmokers: Epidemiologic findings. Am Heart J 1986;lll:932-940
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Epinephrine and the genesis of hypertension. O Frankl Hypertension. 1992;20:583 doi: 10.1161/01.HYP.20.4.583 Hypertension is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1992 American Heart Association, Inc. All rights reserved. Print ISSN: 0194-911X. Online ISSN: 1524-4563
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://hyper.ahajournals.org/content/20/4/583.citation
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Hypertension can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Hypertension is online at: http://hyper.ahajournals.org//subscriptions/
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Letters to the Editor Letters to the Editor will be published, if suitable, as space permits. They should not exceed 1,000 words (typed double-spaced) in length and may be subject to editing or abridgment.
Epinephrine and the Genesis of Hypertension To the Editor. I read with interest in the January 1992 issue of Hypertension the Brief Review by John S. Floras1 entitled "Epinephrine and the Genesis of Hypertension." As a matter of fact he himself puts it wisely: "the epinephrine hypothesis, itself, remains unproven." May I add that there are other facts that disprove this hypothesis, inter allia, the absence of hypertension in smokers, who have no other risk factors.2-3 We know that smoking cigarettes increases the amount of catecholamines in the blood plasma substantially.4-7 Smoking a single cigarette increases the blood pressure, but as stated above, smokers have a lower blood pressure when compared with their nonsmoking counterparts. Also patients who are suffering from pheochromocytoma have increased blood pressure. They have, of course, a very large increase of catecholamines in their blood plasma, but after a successful operation, if they have not developed irreversible changes in their kidneys, their blood pressure returns to its previous level.8 These two instances alone disprove the epinephrine hypothesis of the genesis of hypertension. Otto Frankl Department of Medicine (retired) Chaim Sheba Medical Center Tel-Hashomer Sadder School of Medicine (retired) University of Tel-Aviv Israel
References 1. Floras JS: Epinephrine and the genesis of hypertension. Hypertension 1992;20:l-18 2. Green MS, Jucha E, Luz Y: Blood pressure in smokers and nonsmokers: Epidemiologic findings. Am Heart J 1986;lll:932-94O 3. Benowitz NL, Sharp DS: Inverse relation between serum cotinine concentration and blood pressure in cigarette smokers. Circulation 1989;80:1309-1312 4. Benowitz NL: Clinical pharmacology of nicotine. Anna Rev Med 1986^7:21-32 5. Benowitz NL: Pharmacologic aspects of cigarette smoking and nicotine addiction. N EnglJ Med 1988^19:1318-1330 6. Cryer PE, Haymond MW, Santiago JV, Shah SO: Norepinephrine and epinephrine release and adrenergic mediation on smokingassociated hemodynamic and metabolic events. N EnglJ Med 1976; 295:573-577 7. Siess W, Lorenz R, Roth R, Weber PC: Plasma catecholamines, platelets aggregation and associated thromboxane formation after physical exercise, smoking, or norepinephrine infusion. Circulation 1982;66:45-48 8. Christensen JN: Catecholamines and essential hypertension, (editorial review) Scand J Can Lab Invest 1982;42L21 1-215 The following is in response: To the Editor.
Dr. Frankl raises two interesting issues. Neither directly refutes the epinephrine hypothesis as developed in the review.
An acute bout of heavy smoking will cause marked increases in blood pressure and heart rate in habitual smokers,1 and ambulatory blood pressures are increased by smoking.1-2 These pressor effects of smoking may not be appreciated if blood pressure is recorded during abstinence.1 The two population studies cited by Dr. Frankl do not constitute a rigorous test of the epinephrine hypothesis since they were descriptive rather than mechanistic in design. Pheochromocytomata are interesting in that a neurogenic component to the higher blood pressure of patients harboring such tumors can be unmasked by the clonidine suppression test.3 Epinephrine could act both directly and as a cotransmitter on prejunctional ft adrenergic receptors to increase noradrenergic release and augment neurogenic vasoconstriction in such patients. Approximately 25% of patients exhibit primary hypertension after tumor removal/ Since patients do not ordinarily present with detailed documentation of their blood pressure previous to the development of pheochromocytomata, it cannot be assumed that blood pressure does return to its "previous level" in the remaining 75%. One of the key concepts developed in my review5 is that ft adrenergic receptor-mediated facilitation of norepinephrine release appears to occur only during a period of critical sensitivity to epinephrine. A second point I emphasized is that expression of high blood pressure by this mechanism may be restricted to a specific subset of individuals with a genetic predisposition to primary hypertension. As was concluded, the most compelling interventional tests of the epinephrine hypothesis would require identification of such individuals at the earliest and mildest stage of their disease, well before the development of clinically established hypertension. Neither the broadly based population study of smoking and blood pressure by Green and his colleagues6 (from which 11-15% of subjects screened were excluded because of previously documented hypertension) nor the anecdotal remark on pheochromocytoma cited by Dr. Frankl fulfill these criteria. John S. Fioraii Division of Cardiology Department of Medicine Toronto General Hospital Toronto, Canada
References 1. Groppelli A, Giorgi DMA, Omboni S, Parati G, Mancia G: Persistent blood pressure increase induced by heavy smoking. J Hypertais 1992;10:495-499 2. Schnall PL, Schwartz JE, Landsbergis PA, Warren K, Pickering TG: Relation between job strain, alcohol and ambulatory blood pressure. Hypertension 1992; 19:488-494 3. Bravo EL, Tarazi RC, Fouad FM, Vidt DG, Gifford RW: Clonidinesuppression test. N EnglJ Med 1981^05:623-626 4. Manger WM, Gifford RW: Pheochromocytoma, in Laragh JH, Brenner BM (eds): Hypertension: Pathophysiology, Diagnosis, and Management. New York, Raven Press, Publishers, 1990 5. Floras JS: Epinephrine and the genesis of hypertension. Hypertension 1992;19:1-18 6. Green MS, Jucha E, Luz Y: Blood pressure in smokers and nonsmokers: Epidemiologic findings. Am Heart J 1986;lll:932-940
Downloaded from http://hyper.ahajournals.org/ by guest on May 27, 2015
Epinephrine and the genesis of hypertension. O Frankl Hypertension. 1992;20:583 doi: 10.1161/01.HYP.20.4.583 Hypertension is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1992 American Heart Association, Inc. All rights reserved. Print ISSN: 0194-911X. Online ISSN: 1524-4563
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://hyper.ahajournals.org/content/20/4/583.citation
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Hypertension can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Hypertension is online at: http://hyper.ahajournals.org//subscriptions/
Downloaded from http://hyper.ahajournals.org/ by guest on May 27, 2015
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