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The value of the angiotensin infusion test in the diagnosis of true renovascular hypertension
American
Heart Journal October, 1968, Volume 76, Number
4
Edit'rial The value diagnosis
of the angiotensin of true renovascular
infusion test hypertension
in the
J. Genest, M.D. Montreal, Quebec, Canada
A
t the 1964 LIeeting of the American Society for Clinical Investigation, Kaplan proposed the angiotensin infusion test as diagnostic of true renovascular hypertension. This test consisted of the infusion of an angiotensin solution (0.2 pg per milliliter of 5 per cent glucose in water) at a rate sufficient to obtain a rise of 20 mm. Hg in diastolic blood pressure or until a rate of 20 pg of angiotensin per kilogram body weight per minute was reached. The rate of infusion (nanogram per kilogram body weight per minute) was reported high in all cases of renovascular hypertension in contrast with other hypertensive states (essential, renal, parenchymatous hypertension, and primary aldosteronism), with the exception of malignant hypertension. The results were clear-cut and the test appeared of distinct value. Although it is based on the assumption that the resistance to the pressor effect of exogenous angiotensin was presumably due to already high levels of endogenous angiotensin, no satisfactory explanation was given for the fact that the normal subjects had a response to exogenous angiotensin similar to that shown by the patients with renovascular hypertension. From Vol.
76,
No.
4,
pp.
the
Clinical
443-w
Research October,
Institute
1968
of Montreal,
Not many months went by before the specificity of the test as a diagnostic procedure for true renovascular hypertension was seriously questioned, if not rejected. Veyrat’ emphasized the importance of the sodium balance in the pressor response to angiotensin, a point already made by Kaplan and Silah,2 but probably not sufficiently emphasized. Other workers found high resistance to the pressor effect of exogenous angiotensin in a number of hypertensive patients with renal parenchymatous diseases and in others receiving natriuretic agents. There was also a good deal of confusion in the designation of patients with true renovascular hypertension as separate from those with hypertension associated with renal artery stenosis. In many patients studied, no indication of cure or failure of surgery was given with at least one year’s observation. This makes one doubt whether these patients truly had renovascular hypertension. Finally, two deaths during angiotensin infusions were reported, one in Paris and a second in New York. One of these two deaths was due to a ruptured cerebral aneurysm. This serves to emphasize the definite risk imposed upon patients by the angiotensin infusion, especially when the preinfusion Montreal,
Que.,
Canada.
American
Heart
Journal
443
444
.4m. Hart 1. October, 1908
Genest
diastolic pressure is above 110 to 115 mm. Hg. Since this test was based on the assumption that the decreased pressor responsiveness to exogenous angiotensin in patients with true renovascular hypertension was due to increased levels of endogenous angiotensin, a study was made by Silah and associates3 to confirm this assumption. Previously, in 1965, Genest and co-workers have emphasized the importance of high plasma renin activity levels, of a systolic pressure gradient beyond the stenosis greater than 30 mm. Hg, and the absence of arteriolar changes in the involved kidney as important criteria for the diagnosis of true renovascular hypertension. These studies, emphasizing the importance of plasma renin activity determinations, have since been confirmed by several groups. Using these criteria, Silah and associates have studied three groups of hypertensive patients: (1) those with essential hypertension, (2) those with essential hypertension associated with renal arterial obstruction, and (3) those with true renovascular hypertension (presenting the above criteria and cured by operation). Each patient had been thoroughly studied for plasma electrolytes, renal function, and renal angiography. The mean pressor dose of angiotensin infusion in the patients in Group 3 was 9.8 ng. per kilogram per minute in contrast to 3.8 in those in Groups 1 and 2. The correlation between the pressor dose of infused angiotensin and the patients’ renin activity levels was significant (p < 0.01). The authors emphasized that,
if the test is to be meaningful, strict attention must be given to obtaining a stable basal blood pressure, to the regulation of sodium intake at 120 to 150 mEy. per da>-, by insuring normal blood volume by prior infusion of at least 250 ml. of normal saline, b; a withholding natriuretic drugs, and demonstrating the absence of significant parenchylw;%ous renal diseases. With these reservat; &? the angiotensin infusion test has a xiii value as an adjunct diagnostic tool I& true renovascular hypertension. However, one should always remember the risk involved to the patient’s life in attempting to raise, by 20 mm. Hg, a basal diastolic blood pressure that is nlreadv above 110 to 115 mm. Hg! It is our opinion that the test cannot replace the direct measurement of plasma renin activit>- and that, as soon as this measurement becomes available in more laboratories, the angiotensin infusion test will have outlived its usefulness. REFERESCES
Veyrat, K., Brunner, H. R., Manning, E. I.., rind Muller, 11. F.: Confrontation de I’action pressure de l’angiotensine, du taux de la r&line plasmntique, et de l’a!dost&ronourie chez I’homme.Intern. Club on Arterial Hypertension. First Meetine. Paris. 1966. L’ExDansion Scie;lt. Fr. Editors,-;. 2.59. ’ ’ A Kaplan, N. M., and Silah, J. G.: The effect of angiotensin II on the blood pressure in humans with hypertensive disease, J. Clin. Invest. 43:659,
1964.
Silah, J. G., Strong, C. G., Kowaczynski, I\‘., and Gene& J.: The angiotensin infusion test and peripheral venous renin activity, Cnnad. RI. X. J. 96:1397, 1967.
Heart Journal October, 1968, Volume 76, Number
4
Edit'rial The value diagnosis
of the angiotensin of true renovascular
infusion test hypertension
in the
J. Genest, M.D. Montreal, Quebec, Canada
A
t the 1964 LIeeting of the American Society for Clinical Investigation, Kaplan proposed the angiotensin infusion test as diagnostic of true renovascular hypertension. This test consisted of the infusion of an angiotensin solution (0.2 pg per milliliter of 5 per cent glucose in water) at a rate sufficient to obtain a rise of 20 mm. Hg in diastolic blood pressure or until a rate of 20 pg of angiotensin per kilogram body weight per minute was reached. The rate of infusion (nanogram per kilogram body weight per minute) was reported high in all cases of renovascular hypertension in contrast with other hypertensive states (essential, renal, parenchymatous hypertension, and primary aldosteronism), with the exception of malignant hypertension. The results were clear-cut and the test appeared of distinct value. Although it is based on the assumption that the resistance to the pressor effect of exogenous angiotensin was presumably due to already high levels of endogenous angiotensin, no satisfactory explanation was given for the fact that the normal subjects had a response to exogenous angiotensin similar to that shown by the patients with renovascular hypertension. From Vol.
76,
No.
4,
pp.
the
Clinical
443-w
Research October,
Institute
1968
of Montreal,
Not many months went by before the specificity of the test as a diagnostic procedure for true renovascular hypertension was seriously questioned, if not rejected. Veyrat’ emphasized the importance of the sodium balance in the pressor response to angiotensin, a point already made by Kaplan and Silah,2 but probably not sufficiently emphasized. Other workers found high resistance to the pressor effect of exogenous angiotensin in a number of hypertensive patients with renal parenchymatous diseases and in others receiving natriuretic agents. There was also a good deal of confusion in the designation of patients with true renovascular hypertension as separate from those with hypertension associated with renal artery stenosis. In many patients studied, no indication of cure or failure of surgery was given with at least one year’s observation. This makes one doubt whether these patients truly had renovascular hypertension. Finally, two deaths during angiotensin infusions were reported, one in Paris and a second in New York. One of these two deaths was due to a ruptured cerebral aneurysm. This serves to emphasize the definite risk imposed upon patients by the angiotensin infusion, especially when the preinfusion Montreal,
Que.,
Canada.
American
Heart
Journal
443
444
.4m. Hart 1. October, 1908
Genest
diastolic pressure is above 110 to 115 mm. Hg. Since this test was based on the assumption that the decreased pressor responsiveness to exogenous angiotensin in patients with true renovascular hypertension was due to increased levels of endogenous angiotensin, a study was made by Silah and associates3 to confirm this assumption. Previously, in 1965, Genest and co-workers have emphasized the importance of high plasma renin activity levels, of a systolic pressure gradient beyond the stenosis greater than 30 mm. Hg, and the absence of arteriolar changes in the involved kidney as important criteria for the diagnosis of true renovascular hypertension. These studies, emphasizing the importance of plasma renin activity determinations, have since been confirmed by several groups. Using these criteria, Silah and associates have studied three groups of hypertensive patients: (1) those with essential hypertension, (2) those with essential hypertension associated with renal arterial obstruction, and (3) those with true renovascular hypertension (presenting the above criteria and cured by operation). Each patient had been thoroughly studied for plasma electrolytes, renal function, and renal angiography. The mean pressor dose of angiotensin infusion in the patients in Group 3 was 9.8 ng. per kilogram per minute in contrast to 3.8 in those in Groups 1 and 2. The correlation between the pressor dose of infused angiotensin and the patients’ renin activity levels was significant (p < 0.01). The authors emphasized that,
if the test is to be meaningful, strict attention must be given to obtaining a stable basal blood pressure, to the regulation of sodium intake at 120 to 150 mEy. per da>-, by insuring normal blood volume by prior infusion of at least 250 ml. of normal saline, b; a withholding natriuretic drugs, and demonstrating the absence of significant parenchylw;%ous renal diseases. With these reservat; &? the angiotensin infusion test has a xiii value as an adjunct diagnostic tool I& true renovascular hypertension. However, one should always remember the risk involved to the patient’s life in attempting to raise, by 20 mm. Hg, a basal diastolic blood pressure that is nlreadv above 110 to 115 mm. Hg! It is our opinion that the test cannot replace the direct measurement of plasma renin activit>- and that, as soon as this measurement becomes available in more laboratories, the angiotensin infusion test will have outlived its usefulness. REFERESCES
Veyrat, K., Brunner, H. R., Manning, E. I.., rind Muller, 11. F.: Confrontation de I’action pressure de l’angiotensine, du taux de la r&line plasmntique, et de l’a!dost&ronourie chez I’homme.Intern. Club on Arterial Hypertension. First Meetine. Paris. 1966. L’ExDansion Scie;lt. Fr. Editors,-;. 2.59. ’ ’ A Kaplan, N. M., and Silah, J. G.: The effect of angiotensin II on the blood pressure in humans with hypertensive disease, J. Clin. Invest. 43:659,
1964.
Silah, J. G., Strong, C. G., Kowaczynski, I\‘., and Gene& J.: The angiotensin infusion test and peripheral venous renin activity, Cnnad. RI. X. J. 96:1397, 1967.