- Email: [email protected]
PATHOGENESIS OF ESSENTIAL HYPERTENSION
92 tification of
has been done by measuring moveand areas, and correlations have been found with pregnancy outcome.6 We hope that this information will help our colleagues in Manchester in their future research. F. KUBLI Universitats-Frauenklmik, U. HALLER Heidelberg, H. HENNER West Germany ment
loops,
movements
movement ways,
PATHOGENESIS OF ESSENTIAL HYPERTENSION
SiR,—A hypothesis in the true sense of the word contains the elements of Zadkine’s Rotterdam statue (see figure): the contours are marked and the core is replaced by clear thought, which can be substantiated by means of empirics. If this definition is correct, one of the latest products’ from the Glasgow M.R.C. workers is not a hypothesis. Instead of a clear outline of hard evidence surrounding a new perspective we observe a familiar pattern of worn-out thoughts punctuated by neologisms. We refer to the terms "integrated pressure", "renal transformation time", and "stepwise interaction". Any investigator who tries to measure bloodpressure in a round-the-clock fashion realises that it is virtually impossible to integrate blood-pressure from the records. It is therefore equally impossible to prove or disprove that it is integrated blood-pressure, rather than basal blood-pressures or maximal pressure, which determines the outcome. The existence of an adrenergic drive in the young hypertensive is easy to think of, but very difficult to prove. According to our experience, plasma-noradrenaline concentrations do not rise in the earliest stages of hypertension (unpublished). We were surprised to find that the time-honoured hypothesis of "baroreceptor resetting"-which may be, and has been, put to the test in the laboratory-has been left out of the picture. "Renal transformation time", which as a vascular phenomenon could partly reflect baroreceptor resetting, is far from being a time-related variable. In fact cortical blood-flow is already appreciably decreased in young "labile" hypertensives.9 We would ask the Glasgow workers to be more specific about their concept of the "renal abnormality". Does it merely consist of a vascular alteration, or is there any evidence of intrinsic abnormality in the nephron? If the hydrostatic and oncotic forces surrounding the nephron are balanced at a higher level, does such a process occur throughout the kidney, or is it limited to the outer cortical area paralleling the hoemodynamic changes? The time is past for any theory to lump together the outer cortical and juxtamedullary nephrons, since a discrimination can be made on the basis of structural and functional properties (e.g., sodium handling). The "renal abnormality" is apparently not reflected in plasma-renin concentrations since these were stated to be normal. We have even evidence that they tend to be reduced.’° This suggests a negative rather than a positive feedback mechanism, the kidney playing the role of counteracting the high blood-pressure. Perhaps, then, "the slower, but reversible effect on urinary sodium excretion" is the real mechanism. However, in the same paper Brown et al. note that exchangeable sodium, plasma volume, and extracellular volume are "unremarkable". It should be added that many investigators have observed reduced plasma volumes, and if the data from different laboratories are pooled, the difference is statistically significant"6. Henner,
H., Haller, U., Wolf-Zimper, O., Lorenz, W. J., Bader, R., Müller, B., Kubh, F. Excerpta med. int Congr. Ser. no. 363. Proc. 2nd Eur. Congr. Ultrason. Med. held in Munich, in May, 1975. 7. Brown, J. J., Lever, A. F., Robertson, J. I. S., Schalekamp, M. A. Lancet, 1976, i, 1217. 8. Alam, G. M., Smirk, F H. Br. Heart J 1943, 5, 152. 9. Kolsters, G. Thesis, Rotterdam, 1976. 10. Schalekamp, M. A. D. H., Birkenhäger, W. H., Kolsters, G, Lever, A. F. in Hypertension. Current Problems (edited by A. Distler and H. P. Wolff, p. 133. Stuttgart, 1974 11. Birkenhäger, W. H., Schalekamp, M. A. D. H. Control Mechanisms in Essential Hypertension. Amsterdam (in the press .
0. Zadkine’s Rotterdam statue,
a
model
containing
the elements of
a
hypothesis.
again, therefore, a negative rather than a positive feedback mechanism. Perhaps Brown et al. consider a breakdown of a vasodepressor mechanism. But how would they then visualise "stepwise interaction"? It is to be hoped that they will one day put forward a hypothesis which fully accounts for known facts and which can be tested in the clinical setting.
Department of Internal Medicine, Zuiderziekenhuis, Rotterdam, Netherlands
W. H. BIRKENHÄGER T. L. KHO P. W. DE LEEUW R. VANDONGEN A. WESTER G. A. ZAAL
are surprised by the rather peevish response of friend, Professor Birkenhager, and his colleagues, to our paper (June 5, p. 1217). Even more surprising is their invocation of Zadkine’s statue as a model for scientific hypothesis. The people of Rotterdam more usually regard it as a symbol of indiscriminate aggression.
SIR,-We
our
The criticisms of the Rotterdam workers seem to us to have little substance. We also dislike neologisms, but, with the exception of "renal transformation time", a term we defined, the phrases they object to are already in use. Dealing with more specific points they raise: first, despite their assertions, "integrated pressure" could be derived from continuous measurement of blood-pressure in man.12 Birkenhager has made similar measurements himself. Renal transformation time is also measureable; after 8 weeks, in 50% of rats the kidney is "transformed" and able to maintain
hypertension.4 We are surprised by Professor Birkenhager’s reluctance to accept a role for the kidney in essential hypertension, since this is an idea he has previously proposed5 and defended6 with us.
1. Littler, W A, Honour, A. J, Sleight, P., Stott, F D Br. med J. 1972, iii, 76. 2 Littler, W A , West, M J., Honour, A J, Sleight, P. Proc. 7th Eur Congr. Cardiol 1976, p. 670 abstr. 3. Birkenhager, W H, Houwing, L. A., Van Es, A., Lamers, H. J., Mulder, A H. Clin Sci 1968, 35, 445 4. Floyer, M. A ibid. 1951, 10, 405 5. Kolsters, G., Schalekamp. M A., Birkenhager, W. H, Lever, A. F. in Pathophysiology and Management of Arterial Hypertension (edited by G. Berglund, L. Hansson, and L. Werkö ; p 54, Goteborg, 1975. 6. Birkenhager, W. H, Brown, J J., Lever, A. F, Robertson, J. I. S., Schalekamp, M A. Lancet, 1975, i, 1423
93 of our June 5 hypothesis is that a kidney exposed to increased pressure can maintain the increase when the original cause is removed.4 7 They will find in the paper9 we cited a fair amount of "hard evidence", and also that we have been "more specific" about our concept of the renal abnormality. We are reminded, in a rather mischievous calumny, that "the time is past for any theory to lump together the outer cortical and juxtamedullary nephrons". Professor Birkenhager and his colleagues must be aware that since 1963 we have described anatomical and biochemical differences in outer cortical and juxtamedullary nephrons,"- 12 and have discussed the functional consequences. 12 11 In the precise context of our hypothesis we noted that "an uneven distribution of hydrostatic and oncotic pressure effects (through the renal cortex) would need to be borne in mind".9 Further points are made in their letter -about renin, plasma volume, noradrenaline, and the autonomic nervous system. We are not in disagreement on the inverse correlation of renin with age in essential hypertension. The Rotterdam workers noted this’4 and well and others’6 have confirmed it. We even share as co-authors with Professor Birkenhager the same interpretation.s By drawing attention to occasional subnormal renin levels he merely reinforces the point we were making. Similarly with plasma volume: Schalekamp, Birkenhager, and Leverl’ have reviewed the subject. Most patients with essential hypertension have either normal or slightly decreased volume. In our recent hypothesis we describe plasma volume as "unremarkable" in the sense that it is unlikely to cause essential hypertension unless increased at some stage. In an unpublished study, Professor Birkenhager and his present colleagues find no increase in plasma-noradrenaline in patients with early essential hypertension, and they consider that we make too much of the role of the autonomic nervous system in essential hypertension. Dr Sever18 in an interestingly contrasted letter finds plasma-noradrenaline increased. In his view we underestimate the role of the autonomic nervous system. Both cannot be right. Dr Sever is correct, however, when he says that the evidence from phaeochromocytoma cannot be used to rule out a role for autonomic nervous overactivity in essential hypertension; but this was not what we claimed. The data from phaeochromocytoma are relevant to the point that a rise of plasma-noradrenaline seems insufficient by itself to account for essential hypertension by direct and acute vasoconstriction. The next sentence in our paper deals with Dr Sever’s question. Sir George Pickering also writes about our hypothesis.I9 As he says, we had overlooked his proposal on the pathogenesis of essential hypertension.10 This, like ours, suggests that continued but mild overactivity of one system may raise bloodpressure by affecting a second mechanism. In our hypothesis this second mechanism is in the kidney-in his, it is in the blood-vessels generally. If either is capable of working in this
The
point
7. 8. 9.
Thal, A P., Grage, T. B., Vernier, R. L. Circulation, 1963, 27, 36. Miller, H. C., Phillips, C. E. Surgery Gynec Obstet. 1968, 127, 1274. Brown, J. J., Lever, A. F., Robertson, J. I. S., Schalekamp, M. A. D Lancet, 1974, ii, 320. 10. Brown, J. J., Davies, D. L., Lever, A. F., Parker, R. A., Robertson, J. I. S. ibid, 1963, ii, 668. 11. Brown, J. J., Davies, D. L., Lever, A. F., Parker, R. A., Robertson, J. I. S. Clin Sci. 1966, 30, 223. 12. Gavras, H., Brown, J. J., Lever, A. F., Robertson, J. I. S. ibid. 1970, 38, 409.
"Fire on the heart Let not thv ball mere scratch From dreich munition."
J. J. BROWN M.R.C. Blood Pressure Unit, Western Infirmary, Glasgow G11 6NT
A. F. LEVER J. I. S. ROBERTSON
Academische Ziekenhuis, Rotterdam, Netherlands
M. A. SCHALEKAMP
MYOCARDIAL DAMAGE DUE TO FAULTY HEAT EXCHANGE
SIR,-Although myocardial damage is usually thought to be due
to
thrombosis
or
occlusion of arteries, there is another
pathway which might lead rapidly and irreversibly to myocardial damage. This pathway is a direct result of a slow-down of blood-flow, but is not primarily involved in the decrease of oxygen supply. A slow-down of blood-flow might have another and drastic effect-a decrease of heat exchange, overheating (localised or focal) of the heart resulting in a structural transition of the connective tissue protein, collagen. The heart is a pump with high metabolic activity. Its mean temperature in man is about 38°C, and it produces heat
at a rate of about 2 cal per beat,24 25 blood-flow of about 250 ml/min.26 Factors such as a decrease of blood pH, an increase of blood viscosity and a decrease of blood-flow,27-29 or an increase of heart-rate, lead to an increase of temperature (even if localised) of myocardium and to the possibility that the melting temperature range of molecular collagen is overlapped. This temperature range is 38-40°C in man and other mammals with similar body temperature.30-32 In principle, an increase of temperature into this melting range would not cause irreversible structural damage to collagenous tissue under static conditions, but when mechanical stresses are present (as they are in the heart muscle) then irreversible change in the elastic properties of the tissue is likely. This happens in vitro.3O 31 While even a slightly raised temperature (40°C) may begin to denature some body proteins (e.g., increasing aggregation of red blood-cells33), the low turnover-rate of collagen may mean that damage to it is retained for long periods. Detects might accumulate because the repair-rate is slower than the trauma-
with
a
rate.
21. 22.
Pickering, G. W. Clin. Sci. 1945, 5, 229. Koletsky, S., Rivera-Velez, J. M J. Lab. clin. Med. 1970, 76,
54
Flover, M. A. Br. med. Bull. 1957, 13, 29. 24. Hill, A. V. Physiol. Rev. 1922, 11, 310 25. Hill, A. V., Hartree, W. J. Physiol, Lond 1920, 54, 84 26. Schlant, R. D in The Heart (edited by J. Willis Hurst, p 74 New York, 23.
13.
Brown, J. J., Chinn, R. H., Gavras, H., Leckie, B., Lever, A. F., McGregor, J, Morton, J. J., Robertson, J. I. S. in Hypertension 72 (edited by J. Genest and E Kolw), p. 81. Berlin, 1972. 14. Schalekamp, M. A. D. H., Schalekamp-Kuyken, M P. A., Birkenhäger, W. H. Clin Sci. 1970, 38, 101. 15. Padfield, P. L., Beevers, D. G., Brown, J. J, Davies, D. L., Lever, A. F, Robertson, J. I. S., Schalekamp, M. A D., Tree, M Lancet, 1975, i, 548. 16 Tuck, M L., Williams, C. H., Cain, J. P, Sullivan, J. M., Dluhy, R. G. Am. J. Cardiol. 1973, 32, 637 17. Schalekamp, M. A., Birkenhäger, W. H., Lever, A. F. in An International Textbook on Hypertension (edited by J. Genest). New York (in the press) 18. Sever, P S. Lancet, 1976, i, 1404. 19 Pickering, G. W. ibid. p. 1403. 20. Pickering, G. W. The Nature of Essential
way it must be able to maintain an increase of pressure when the original cause is removed. The kidney has this property4 78 but there is also a non-renal mechanism or component.z’-z3 To decide whether one, both, or neither is at work in essential hypertension is important and testable, but we shall not use the hole in Zadkine’s statue for this purpose. While re-examining the statue, Professor Blrkenhãger might like to consider one of our own local legends: during the 18th century James MacGregor was shot in nearby Glen Fruin for stealing sheep. Professor Birkenhager has visited us m Glasgow and he may remember MacGregor’s last words to his executioners :
Hypertension, London,
1961
1974. L Blood Microrheology; Viscosity Factors in Blood Flow, Ischæmia and Thrombosis. London, 1971. 28. Dintenfass, L., Read, J. Lancet, 1968, i, 570. 29. Dintenfass, L. Hœmatologia, 1968, 2, 19 30. Rigby, B J. in Chemical Dynamics (edited by Hirschfelder , p. 537 New York, 1971 31 Rigby, B. J., Bloch, B., Mason, P. Med. J. Aust. 1966. i. 46 32. von Hippel, P. H in A Treatise on Collagen (edited by Ramachandran. vol. i, p. 253 New York, 1967 33. Dintenfass, L., Forbes, C. D. Biorheology, 1973, 10, 383. 27.
Dintenfass,
has been done by measuring moveand areas, and correlations have been found with pregnancy outcome.6 We hope that this information will help our colleagues in Manchester in their future research. F. KUBLI Universitats-Frauenklmik, U. HALLER Heidelberg, H. HENNER West Germany ment
loops,
movements
movement ways,
PATHOGENESIS OF ESSENTIAL HYPERTENSION
SiR,—A hypothesis in the true sense of the word contains the elements of Zadkine’s Rotterdam statue (see figure): the contours are marked and the core is replaced by clear thought, which can be substantiated by means of empirics. If this definition is correct, one of the latest products’ from the Glasgow M.R.C. workers is not a hypothesis. Instead of a clear outline of hard evidence surrounding a new perspective we observe a familiar pattern of worn-out thoughts punctuated by neologisms. We refer to the terms "integrated pressure", "renal transformation time", and "stepwise interaction". Any investigator who tries to measure bloodpressure in a round-the-clock fashion realises that it is virtually impossible to integrate blood-pressure from the records. It is therefore equally impossible to prove or disprove that it is integrated blood-pressure, rather than basal blood-pressures or maximal pressure, which determines the outcome. The existence of an adrenergic drive in the young hypertensive is easy to think of, but very difficult to prove. According to our experience, plasma-noradrenaline concentrations do not rise in the earliest stages of hypertension (unpublished). We were surprised to find that the time-honoured hypothesis of "baroreceptor resetting"-which may be, and has been, put to the test in the laboratory-has been left out of the picture. "Renal transformation time", which as a vascular phenomenon could partly reflect baroreceptor resetting, is far from being a time-related variable. In fact cortical blood-flow is already appreciably decreased in young "labile" hypertensives.9 We would ask the Glasgow workers to be more specific about their concept of the "renal abnormality". Does it merely consist of a vascular alteration, or is there any evidence of intrinsic abnormality in the nephron? If the hydrostatic and oncotic forces surrounding the nephron are balanced at a higher level, does such a process occur throughout the kidney, or is it limited to the outer cortical area paralleling the hoemodynamic changes? The time is past for any theory to lump together the outer cortical and juxtamedullary nephrons, since a discrimination can be made on the basis of structural and functional properties (e.g., sodium handling). The "renal abnormality" is apparently not reflected in plasma-renin concentrations since these were stated to be normal. We have even evidence that they tend to be reduced.’° This suggests a negative rather than a positive feedback mechanism, the kidney playing the role of counteracting the high blood-pressure. Perhaps, then, "the slower, but reversible effect on urinary sodium excretion" is the real mechanism. However, in the same paper Brown et al. note that exchangeable sodium, plasma volume, and extracellular volume are "unremarkable". It should be added that many investigators have observed reduced plasma volumes, and if the data from different laboratories are pooled, the difference is statistically significant"6. Henner,
H., Haller, U., Wolf-Zimper, O., Lorenz, W. J., Bader, R., Müller, B., Kubh, F. Excerpta med. int Congr. Ser. no. 363. Proc. 2nd Eur. Congr. Ultrason. Med. held in Munich, in May, 1975. 7. Brown, J. J., Lever, A. F., Robertson, J. I. S., Schalekamp, M. A. Lancet, 1976, i, 1217. 8. Alam, G. M., Smirk, F H. Br. Heart J 1943, 5, 152. 9. Kolsters, G. Thesis, Rotterdam, 1976. 10. Schalekamp, M. A. D. H., Birkenhäger, W. H., Kolsters, G, Lever, A. F. in Hypertension. Current Problems (edited by A. Distler and H. P. Wolff, p. 133. Stuttgart, 1974 11. Birkenhäger, W. H., Schalekamp, M. A. D. H. Control Mechanisms in Essential Hypertension. Amsterdam (in the press .
0. Zadkine’s Rotterdam statue,
a
model
containing
the elements of
a
hypothesis.
again, therefore, a negative rather than a positive feedback mechanism. Perhaps Brown et al. consider a breakdown of a vasodepressor mechanism. But how would they then visualise "stepwise interaction"? It is to be hoped that they will one day put forward a hypothesis which fully accounts for known facts and which can be tested in the clinical setting.
Department of Internal Medicine, Zuiderziekenhuis, Rotterdam, Netherlands
W. H. BIRKENHÄGER T. L. KHO P. W. DE LEEUW R. VANDONGEN A. WESTER G. A. ZAAL
are surprised by the rather peevish response of friend, Professor Birkenhager, and his colleagues, to our paper (June 5, p. 1217). Even more surprising is their invocation of Zadkine’s statue as a model for scientific hypothesis. The people of Rotterdam more usually regard it as a symbol of indiscriminate aggression.
SIR,-We
our
The criticisms of the Rotterdam workers seem to us to have little substance. We also dislike neologisms, but, with the exception of "renal transformation time", a term we defined, the phrases they object to are already in use. Dealing with more specific points they raise: first, despite their assertions, "integrated pressure" could be derived from continuous measurement of blood-pressure in man.12 Birkenhager has made similar measurements himself. Renal transformation time is also measureable; after 8 weeks, in 50% of rats the kidney is "transformed" and able to maintain
hypertension.4 We are surprised by Professor Birkenhager’s reluctance to accept a role for the kidney in essential hypertension, since this is an idea he has previously proposed5 and defended6 with us.
1. Littler, W A, Honour, A. J, Sleight, P., Stott, F D Br. med J. 1972, iii, 76. 2 Littler, W A , West, M J., Honour, A J, Sleight, P. Proc. 7th Eur Congr. Cardiol 1976, p. 670 abstr. 3. Birkenhager, W H, Houwing, L. A., Van Es, A., Lamers, H. J., Mulder, A H. Clin Sci 1968, 35, 445 4. Floyer, M. A ibid. 1951, 10, 405 5. Kolsters, G., Schalekamp. M A., Birkenhager, W. H, Lever, A. F. in Pathophysiology and Management of Arterial Hypertension (edited by G. Berglund, L. Hansson, and L. Werkö ; p 54, Goteborg, 1975. 6. Birkenhager, W. H, Brown, J J., Lever, A. F, Robertson, J. I. S., Schalekamp, M A. Lancet, 1975, i, 1423
93 of our June 5 hypothesis is that a kidney exposed to increased pressure can maintain the increase when the original cause is removed.4 7 They will find in the paper9 we cited a fair amount of "hard evidence", and also that we have been "more specific" about our concept of the renal abnormality. We are reminded, in a rather mischievous calumny, that "the time is past for any theory to lump together the outer cortical and juxtamedullary nephrons". Professor Birkenhager and his colleagues must be aware that since 1963 we have described anatomical and biochemical differences in outer cortical and juxtamedullary nephrons,"- 12 and have discussed the functional consequences. 12 11 In the precise context of our hypothesis we noted that "an uneven distribution of hydrostatic and oncotic pressure effects (through the renal cortex) would need to be borne in mind".9 Further points are made in their letter -about renin, plasma volume, noradrenaline, and the autonomic nervous system. We are not in disagreement on the inverse correlation of renin with age in essential hypertension. The Rotterdam workers noted this’4 and well and others’6 have confirmed it. We even share as co-authors with Professor Birkenhager the same interpretation.s By drawing attention to occasional subnormal renin levels he merely reinforces the point we were making. Similarly with plasma volume: Schalekamp, Birkenhager, and Leverl’ have reviewed the subject. Most patients with essential hypertension have either normal or slightly decreased volume. In our recent hypothesis we describe plasma volume as "unremarkable" in the sense that it is unlikely to cause essential hypertension unless increased at some stage. In an unpublished study, Professor Birkenhager and his present colleagues find no increase in plasma-noradrenaline in patients with early essential hypertension, and they consider that we make too much of the role of the autonomic nervous system in essential hypertension. Dr Sever18 in an interestingly contrasted letter finds plasma-noradrenaline increased. In his view we underestimate the role of the autonomic nervous system. Both cannot be right. Dr Sever is correct, however, when he says that the evidence from phaeochromocytoma cannot be used to rule out a role for autonomic nervous overactivity in essential hypertension; but this was not what we claimed. The data from phaeochromocytoma are relevant to the point that a rise of plasma-noradrenaline seems insufficient by itself to account for essential hypertension by direct and acute vasoconstriction. The next sentence in our paper deals with Dr Sever’s question. Sir George Pickering also writes about our hypothesis.I9 As he says, we had overlooked his proposal on the pathogenesis of essential hypertension.10 This, like ours, suggests that continued but mild overactivity of one system may raise bloodpressure by affecting a second mechanism. In our hypothesis this second mechanism is in the kidney-in his, it is in the blood-vessels generally. If either is capable of working in this
The
point
7. 8. 9.
Thal, A P., Grage, T. B., Vernier, R. L. Circulation, 1963, 27, 36. Miller, H. C., Phillips, C. E. Surgery Gynec Obstet. 1968, 127, 1274. Brown, J. J., Lever, A. F., Robertson, J. I. S., Schalekamp, M. A. D Lancet, 1974, ii, 320. 10. Brown, J. J., Davies, D. L., Lever, A. F., Parker, R. A., Robertson, J. I. S. ibid, 1963, ii, 668. 11. Brown, J. J., Davies, D. L., Lever, A. F., Parker, R. A., Robertson, J. I. S. Clin Sci. 1966, 30, 223. 12. Gavras, H., Brown, J. J., Lever, A. F., Robertson, J. I. S. ibid. 1970, 38, 409.
"Fire on the heart Let not thv ball mere scratch From dreich munition."
J. J. BROWN M.R.C. Blood Pressure Unit, Western Infirmary, Glasgow G11 6NT
A. F. LEVER J. I. S. ROBERTSON
Academische Ziekenhuis, Rotterdam, Netherlands
M. A. SCHALEKAMP
MYOCARDIAL DAMAGE DUE TO FAULTY HEAT EXCHANGE
SIR,-Although myocardial damage is usually thought to be due
to
thrombosis
or
occlusion of arteries, there is another
pathway which might lead rapidly and irreversibly to myocardial damage. This pathway is a direct result of a slow-down of blood-flow, but is not primarily involved in the decrease of oxygen supply. A slow-down of blood-flow might have another and drastic effect-a decrease of heat exchange, overheating (localised or focal) of the heart resulting in a structural transition of the connective tissue protein, collagen. The heart is a pump with high metabolic activity. Its mean temperature in man is about 38°C, and it produces heat
at a rate of about 2 cal per beat,24 25 blood-flow of about 250 ml/min.26 Factors such as a decrease of blood pH, an increase of blood viscosity and a decrease of blood-flow,27-29 or an increase of heart-rate, lead to an increase of temperature (even if localised) of myocardium and to the possibility that the melting temperature range of molecular collagen is overlapped. This temperature range is 38-40°C in man and other mammals with similar body temperature.30-32 In principle, an increase of temperature into this melting range would not cause irreversible structural damage to collagenous tissue under static conditions, but when mechanical stresses are present (as they are in the heart muscle) then irreversible change in the elastic properties of the tissue is likely. This happens in vitro.3O 31 While even a slightly raised temperature (40°C) may begin to denature some body proteins (e.g., increasing aggregation of red blood-cells33), the low turnover-rate of collagen may mean that damage to it is retained for long periods. Detects might accumulate because the repair-rate is slower than the trauma-
with
a
rate.
21. 22.
Pickering, G. W. Clin. Sci. 1945, 5, 229. Koletsky, S., Rivera-Velez, J. M J. Lab. clin. Med. 1970, 76,
54
Flover, M. A. Br. med. Bull. 1957, 13, 29. 24. Hill, A. V. Physiol. Rev. 1922, 11, 310 25. Hill, A. V., Hartree, W. J. Physiol, Lond 1920, 54, 84 26. Schlant, R. D in The Heart (edited by J. Willis Hurst, p 74 New York, 23.
13.
Brown, J. J., Chinn, R. H., Gavras, H., Leckie, B., Lever, A. F., McGregor, J, Morton, J. J., Robertson, J. I. S. in Hypertension 72 (edited by J. Genest and E Kolw), p. 81. Berlin, 1972. 14. Schalekamp, M. A. D. H., Schalekamp-Kuyken, M P. A., Birkenhäger, W. H. Clin Sci. 1970, 38, 101. 15. Padfield, P. L., Beevers, D. G., Brown, J. J, Davies, D. L., Lever, A. F, Robertson, J. I. S., Schalekamp, M. A D., Tree, M Lancet, 1975, i, 548. 16 Tuck, M L., Williams, C. H., Cain, J. P, Sullivan, J. M., Dluhy, R. G. Am. J. Cardiol. 1973, 32, 637 17. Schalekamp, M. A., Birkenhäger, W. H., Lever, A. F. in An International Textbook on Hypertension (edited by J. Genest). New York (in the press) 18. Sever, P S. Lancet, 1976, i, 1404. 19 Pickering, G. W. ibid. p. 1403. 20. Pickering, G. W. The Nature of Essential
way it must be able to maintain an increase of pressure when the original cause is removed. The kidney has this property4 78 but there is also a non-renal mechanism or component.z’-z3 To decide whether one, both, or neither is at work in essential hypertension is important and testable, but we shall not use the hole in Zadkine’s statue for this purpose. While re-examining the statue, Professor Blrkenhãger might like to consider one of our own local legends: during the 18th century James MacGregor was shot in nearby Glen Fruin for stealing sheep. Professor Birkenhager has visited us m Glasgow and he may remember MacGregor’s last words to his executioners :
Hypertension, London,
1961
1974. L Blood Microrheology; Viscosity Factors in Blood Flow, Ischæmia and Thrombosis. London, 1971. 28. Dintenfass, L., Read, J. Lancet, 1968, i, 570. 29. Dintenfass, L. Hœmatologia, 1968, 2, 19 30. Rigby, B J. in Chemical Dynamics (edited by Hirschfelder , p. 537 New York, 1971 31 Rigby, B. J., Bloch, B., Mason, P. Med. J. Aust. 1966. i. 46 32. von Hippel, P. H in A Treatise on Collagen (edited by Ramachandran. vol. i, p. 253 New York, 1967 33. Dintenfass, L., Forbes, C. D. Biorheology, 1973, 10, 383. 27.
Dintenfass,