Donate Help Contact The AHA Sign In Home
American Heart Association
Hypertension
Search: search_blue_button Advanced Search
« Previous Article | Table of Contents | Next Article »
Hypertension. 2001;38:1246-1249
doi: 10.1161/hy1201.101214
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Basso, N.
Right arrow Articles by Terragno, N. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Basso, N.
Right arrow Articles by Terragno, N. A.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH

(Hypertension. 2001;38:1246.)
© 2001 American Heart Association, Inc.

Historical Perspective

History About the Discovery of the Renin-Angiotensin System

Nidia Basso; Norberto A. Terragno

Instituto de Investigaciones Cardiológicas, Facultad de Medicina. Universidad de Buenos Aires, Buenos Aires, Argentina.

Correspondence to Nidia Basso, Instituto de Investigaciones Cardiológicas, Marcelo T. de Alvear 2270, C1122AAJ Buenos Aires, Argentina. E-mail nidiabasso{at}yahoo.com

Abstract

The history of the discovery of the renin-angiotensin system began in 1898 with the studies made by Tigerstedt and Bergman, who reported the pressor effect of renal extracts; they named the renal substance renin based on its origin. In 1934, Harry Goldblatt induced experimental hypertension in dogs by clamping a renal artery. About 1936, simultaneously in the Medical School of the University of Buenos Aires, Argentina, and in the Eli-Lilly Laboratories in Indianapolis, 2 independent groups of researchers, using the Goldblatt technique to produce experimental hypertension, demonstrated renal secretion of a pressor agent similar to renin. In the following years, both teams described the presence of a new compound in the renal vein blood of ischemic kidneys. This agent was extracted from blood with 70% acetone and had a short pressor effect. The final conclusion was that renin acted enzymatically on a plasma protein to produce the new substance. In Buenos Aires, it was called hypertensin; in the United States, angiotonin. In 1958, Eduardo Braun Menéndez from Argentina and Irving H. Page from the United States agreed to name it angiotensin.


Key Words: renin • angiotonin • angiotensin • renin substrate • renin activator

The first observation linking renal disease to left ventricle hypertrophy was reported by Richard Bright in 1836.1 He related hypertrophy to an increased resistance to blood flow in the small vessels due to the altered condition of the blood. In 1868, George Johnson,2 reporting studies on nephritis, suggested that hyaline-fibroid alterations in the renal vessels were due to an impure condition of the blood, which was also responsible for left ventricular hypertrophy. F.A. Mahomed,3 using a primitive sphygmograph for the first time, described high blood pressure in 1872. He also linked left ventricular hypertrophy to hypertension due to nephritis and reported the presence of high blood pressure in patients without renal disease.4,5 Finally, Riva-Rocci,6 in 1896, described the first indirect sphygmomanometer to measure arterial pressure in humans, and in 1905, Korotkoff7 defined the sounds that are named after him.

The relationship between pathological alterations in the kidney and the development of systemic arterial hypertension had been postulated for many years. In this sense, Franz Volhard8 suggested the existence of a circulating vasopressor substance. He classified the hypertensive patients: those with slight vascular damage as reds, and those with important vascular lesions—mostly in the kidney, pale skin, and cerebral damage (malignant hypertension)—as white.

On the other hand, by the end of the nineteenth century, Tigerstedt, a Finnish professor of physiology working at the Karolinska Institute, and his assistant Bergman9 analyzed the effect of renal extracts on arterial pressure. They discovered the presence of a pressor compound in the renal tissue of the rabbit, and based on its origin, they named it renin. The pressor activity could be extracted with glycerin, did not dialyze, and was stable at 56°C and was destroyed by boiling. Moreover, they showed that the renal vein blood increased blood pressure when injected into nephrectomized animals. They also detected the potentiation and protraction of the pressor response to renin in the nephrectomized recipient. They explained that the association between renal disease and cardiac hypertrophy was due to the kidney release of a vasoactive substance that induced contraction of the blood vessels through a direct action.

Based on these facts, many attempts were performed to develop an experimental model of arterial hypertension by manipulation of the renal function. Reduction of the renal mass, X irradiation of the kidney, renal artery occlusion, renal vein constriction, and wrapping of the kidney with a membrane were tested. Results were unreliable, probably as a consequence of inappropriate techniques and/or inadequate methods to measure blood pressure. The first successful experiment was performed by Goldblatt et al in 1934,10 and their technique led to the discovery of the active polypeptide. These researchers linked the ischemic characteristic of the renal disease with hypertension. They induced the experimental hypertension in the dog by the partial constriction of the renal artery using a silver clip. Their results were confirmed by several groups,11 and the search for the mechanisms involved for the increase in blood pressure began. The section of the sympathetic nervous system that regulates the vasomotor mechanisms did not prevent or abolish the development of hypertension.

Goldblatt had already proposed the existence of a humoral mechanism due to the release of a pressor substance by the kidney,12 even though he recognized that this possibility was only sustained by indirect evidences. This concept was not new, Volhard had suggested the presence of a vasoconstrictor factor causing malignant, or "pale," hypertension. Nonetheless, neither he nor his collaborators could establish the nature of such an agent in the circulation of patients suffering from this pathology. Lack of its detection was probably due to inadequate methods for analysis.

Two research groups, working independently, simultaneously reached similar conclusions on this matter. One of them was investigating at the University of Buenos Aires, Argentina, under the leadership of Dr Bernardo Houssay at the Physiology Institute of the School of Medicine. The other group pursued their studies at the Eli Lilly Research Laboratories in Indianapolis, under the leadership of Dr Irvine H. Page.

The discovery of the renin-angiotensin system in Buenos Aires began with the arrival of Dr Juan C. Fasciolo, a young physician, at the Institute chaired by Dr Houssay. He was interested in performing his doctoral thesis in physiology under the direction of Prof Houssay. The subject, selected by Houssay, was to repeat the experiment described by Goldblatt in the dog to find out the nature of the mechanisms involved in the development of high blood pressure. The interest of Dr Houssay in this problem was related to the fact that one of his young disciples, 32-year-old Dr J. Guglielmetti, had recently died of malignant hypertension.

They faced all kind of problems, but finally the development of an adequate silver clip resulted in a number of hypertensive dogs. This first stage was followed by the detection of a vasoactive agent.13 The presence of a pressor compound in the ischemic kidney had been analyzed by several investigators14–16 injecting renal extracts, obtained from hypertensive animals, into the circulation of dogs or rat, while recording changes in blood pressure at the same time. However, the results were not conclusive, even though these preparations produced higher pressures than those obtained from normal animals. In contrast, the presence of a pressor substance in the circulation of hypertensive animals had always been negative.17–19 Finally, only 1 experiment, using a cross circulation between a donor hypertensive dog and a nephrectomized recipient dog, revealed a significant increase in the blood pressure of the recipient dog.20 Thus, the recipient dog had to be nephrectomized.

Based on these findings, an experiment was designed to search for the presence of a pressor agent in the venous blood of the ischemic kidney. Grafting of an ischemic kidney into the neck of a recently nephrectomized dog was chosen. Blood pressure of the dog began to rise shortly after the grafting, and it remained elevated even after the graft was eliminated, supporting the presence of a true pressor secretion. Moreover, grafting a kidney from a normal dog did not show a pressor action. These results were later confirmed by other authors.21–23 Further support for the release of a pressor substance was afforded by the experiments of Dr Alberto C. Taquini, head of research at the Physiology Institute. He added strong evidence supporting the secretion of a vasoactive agent from the ischemic kidney.24–26 Indeed, plasma obtained from the renal vein blood of the ischemic kidney, diluted with saline and injected in the well-known preparation of Lawen-Trendelenburg, produced a strong constrictor effect on the isolated vascular bed of the hind-leg of the toad. The venous plasma from numerous ischemic kidneys of hypertensive dogs always induced a significant and immediate vasoconstrictor effect. To the contrary, venous plasma from normal kidneys had little or no pressor action.

Experimental results had demonstrated that in the acute period, the ischemic kidney of the hypertensive dog released a vasoconstrictor agent.27 It became necessary to establish the nature of this compound and to characterize, purify, and isolate it to identify its chemical structure.

In 1938, Taquini went to the United States with a 2-year fellowship. And, at the same time, Eduardo Braun Menéndez returned from his stay in England, where he had studied the metabolism of the heart with Dr Lovatt Evans. He planned to continue his work on this subject after returning to Buenos Aires. However, when he returned he had to replace Taquini as head of research, he learned of the promising experiments that were being developed in the field of arterial hypertension. He decided to lead a team that also included Drs Juan C. Fasciolo, Luis F. Leloir, and Juan M. Muñoz. Leloir and Muñoz were already involved in studies related to the chemical nature of physiological enzymatic processes.

Some authors17,28,29 had previously described a significant increase in arterial blood pressure, a few minutes after inducing renal ischemia in the dog. This increase was probably due to the secretion of the same vasoactive substance under their study. Therefore, the next step was to perfuse dog kidneys after a short period of ischemia. Braun Menéndez and Fasciolo demonstrated that in acute ischemia, the blood coming from the renal vein induced a strong pressor effect when injected in the circulation of nephrectomized dogs.30 The pharmacological characteristics of this pressor agent indicated that its effect was not modified by the action of atropine, cocaine, or sympatholytic agents and that it was potentiated after bilateral nephrectomy of the recipient animal.31

The following goal now was to isolate the active substance from the blood. Extraction of the active principle was accomplished with acetone (70%). This compound produced a quick pressor action of very short duration, thus completely different from renin. On the other hand, the agent was thermostable and soluble in acetone, and it was not detected in the venous blood of an intact kidney.32 It had a strong vasoconstrictor action on the vascular bed of the toad. These chemical and pharmacological characteristics were different from those of all the known substances at that time. The logic conclusion was that a new compound had been isolated from the blood coming from the ischemic kidney. Based on its properties and effects, it was named hypertensin.

Renin, the pressor principle obtained from renal extracts by Tigerstedt and Bergman in 1898, was thermolabile and had a prolonged pressor effect. This action was recorded when studying renal grafts from hypertensive dogs and also when injecting blood coming from acute ischemic kidneys. Previous observations, therefore, linked renin with the newly discovered agent. However, the nature of the relationship between the 2 compounds remained unknown.

The first studies designed to clarify this matter were unsuccessful. Kidney slices were incubated with plasma (under hypoxic conditions). The release of the active principle could not be detected, probably because of the enzymatic destruction of the formed angiotensin. Then, they incubated a semipurified kidney extract with plasma and were able to isolate a vasoconstrictor substance similar to hypertensin. The compound was soluble in 75% acetone and in glacial acetic acid, was insoluble in ether and amyl alcohol, and was resistant to acid hydrolysis and dialyzable. These characteristics were different from those of renin, epinephrine, tyramine, vasopressin, and urohipertensin.32

Based on these results, the Argentine group described, for the first time, renin as an enzyme similar to papain (protease), which could act on a protein present in the plasma to release hypertensin as the final product of the enzymatic reaction.

Through subsequent experiments, these researchers demonstrated that renin was secreted by the kidney, and hypertensin was formed in the plasma33 from a proteic substrate that was named hypertensinogen because it was the actual origin of the active principle. Blood, as well as kidney, was able to inactivate hypertensin through the action of other enzymes that were called hypertensinases.33 Inactivation of hypertensin was avoided by purifying preparations containing either renin or hypertensinogen.

The fact that bilateral nephrectomy increased considerably the plasma concentration of hypertensinogen was also demonstrated.33 At the same time, the specificity of the enzymatic system was described. Hog renin could not release hypertensin from the human plasma substrate, whereas human renin was able to hydrolyze hog and cow hypertensinogen.34

The hepatic origin of renin substrate was suggested by Page et al.35 However, conclusive experiments were performed later by Leloir et al36 in nephrectomized dogs with and without hepatectomy.

All the research performed on the renin-angiotensin system by the Argentine group were published in a book in 1943.37

Simultaneously, Page, working with Helmer and Kohlstaedt, was investigating the mechanism of action of renin.38 They had observed that when the purified protein was injected in the dog isolated tail preparation and perfused with Ringer solution, it was barely active compared with the strong constrictor and pressor effect obtained after intravenous injection. They postulated the existence of a blood component that was necessary for the vasoactive action of renin. They had observed that the addition of small amounts of plasma to the Ringer’s solution containing purified renin induced a strong vasoconstrictor effect in the perfused dog tail preparation. They concluded that renin was an inactive enzyme that was activated by yet another enzyme, belonging to the kinase group, that was present in the proteic fraction of plasma and blood. Therefore, this plasma protein compound was named renin activator. The final product, a pressor substance formed through the interaction of renin and its activator, was named angiotonin38–41 and was, probably, the actual effector of the renin pressor action.

The similarity between renin substrate and renin activator was immediately accepted, as was the identity of the final product. Moreover, the enzymatic nature of the renin system and the peptidic nature of the hypertensin was also confirmed. Renin acted as a hormone and as an enzyme with a pressor effect that was due to angiotensin release. Shortly after, Page et al42 changed the name of renin activator to renin substrate to emphasize the enzymatic nature of the system. During the following years, both nomenclatures were used, generating a certain degree of confusion.

Synthesis of the octapeptide was successfully accomplished, for the first time, by the group led by Dr Page, then in Cleveland,43 and by Dr Schwyzer in Basil, Switzerland.44,45 The Basil group, working at the CIBA laboratories, marketed the octapeptide under the name Hypertensin4.46

To commemorate the 25-year anniversary of Goldblatt’s first successful experiment to induce arterial hypertension by renal ischemia in the dog, the University of Michigan Regional Conference on the Basic Mechanisms of Arterial Hypertension was held in Ann Arbor, Mich, in 1957 under the Organizing Committee of Drs Sibley W. Hoobler and David F. Bohr. (Under the direction of these 2 distinguished investigators, several Argentine physicians were trained.) Back in Argentina, they continued to work on the mechanisms of arterial hypertension and on the renin-angiotensin system. Among them were Dr. Alberto Agrest, Pedro C. Blaquier, Alberto C. Taquini, Jr, and Ignacio J. de la Riva. All returned to work at the Instituto de Investigaciones Cardiológicas of the School of Medicine of the University of Buenos Aires, where they had begun their research studies. Dr Braun Menéndez et al47 and Dr Alberto C. Taquini et al48 presented their experimental results at the University of Michigan conference, and the results were published in a supplement to Circulation. Also at this meeting, Dr Braun Menéndez (for the Argentine team) and Dr Page (for the American group) arrived at a single nomenclature for the components of the enzymatic system.49 Even though there was already a marketed name of Hypertensin, Braun Menéndez agreed to name the active final compound angiotensin, taking half of each original name. Similarly, the renin substrate was named angiotensinogen, and the enzymes that metabolize the peptide were termed angiotensinases.

A few years were needed for the general acceptance of the new nomenclature. The leading groups in the United States, like those of Goldblatt and Skeggs, and in Europe continued using the Argentine name. In 1959, Dr Braun Menéndez died, and in 1961, Taquini et al50 insisted on the necessity of using the unified nomenclature.

Those involved in the discovery of the renin-angiotensin system probably did not imagine the importance and transcendent significance of their findings as well as the enormous flow of information added to the knowledge of the enzymatic system. In spite of the fact that >50 years have elapsed, the role of the full implications of the renin-angiotensin system on the development of renal arterial hypertension has not been completely elucidated. Notwithstanding, there are no doubts about the beneficial effect of inhibition of the enzymatic system in a group of essential hypertensive patients. In this sense, drugs that are able to block the effect of angiotensin II have contributed to modify the evolution of arterial hypertension and to increase the lifespan of the hypertensive patients.

Received October 10, 2001; first decision October 10, 2001; accepted October 18, 2001.

References

  1. Bright R. Tubular view of the morbid appearances in 100 cases connected with albuminous urine: With observations. Guy’s Hosp Rep. 1836; 1: 380–400.
  2. Johnson GI. On certain points in the anatomy and pathology of Bright’s diseases of the kidney, II: on the influence of the minute blood-vessels upon the circulation. Med Chir Trans. 1868; 51: 57–80.
  3. Mahomed FA. The physiology and clinical use of the sphygmograph. Med Times Gaz. 1872; 1: 62–64.
  4. Mahomed FA. On the sphygmographic evidence of arterio-capillary fibrosis. Trans Path Soc. 1877; 28: 394–397.
  5. Mahomed FA. Chronic Bright’s disease without albuminuria. Guy’s Hosp Rep. 1881; 25: 295–416.
  6. Riva-Rocci S. Un nuovo sfigmomanometro. Gazz Med Torino. 1896; 47: 981–1001.
  7. Korotkoff NS. On methods of studying blood pressure. Izv Voennomed Akad. 1905; 11: 365–370.
  8. Volhard F. Nieren und ableitende Harnwege.. In: Bergmann G, Staehelin R, eds. Handbuch der Inneren Medizin, vol 6. Berlin: Springer Verlag; 1931: 1–1023.
  9. Tigerstedt R, Bergman PG. Niere und Kreislauf. Skand Arch Physiol. 1898; 8: 223–271.
  10. Goldblatt H, Lynch J, Hanzal RF, Summerville WW. Studies on experimental hypertension, I: the production of persistent elevation of systolic blood pressure by means of renal ischemia. J Exp Med. 1934; 59: 347–379.[Abstract]
  11. Freeman NE, Page IH. Hypertension produced by constriction of the renal artery in sympathectomized dogs. Am Heart J. 1937; 14: 405–414.
  12. Goldblatt H. Studies on experimental hypertension, V: the pathogenesis of experimental hypertension due to renal ischemia. Ann Intern Med. 1937; 11: 69–103.
  13. Houssay BA, Fasciolo JC. Demostración del mecanismo humoral de la hipertensión nefrógena. Bol Acad Nac Med. 1937; 18: 342–344.
  14. Harrison TR, Blalock A, Mason MF. Effect on blood pressure of injection of kidney extracts of dogs with renal hypertension. Proc Soc Exp Biol. 1937; 35: 38–40.
  15. Harrison TR, Blalock A, Mason MF, Williams JR. Relation of kidneys to blood pressure: effects of extracts of kidneys of normal dogs and of dogs with renal hypertension on blood pressure of rats. Arch Intern Med. 1937; 60: 1058–1068.
  16. Prinzmetal M, Friedman B. Pressor effects of kidney extracts from patients and dogs with hypertension. Proc Soc Exp Biol. 1937; 35: 122–124.
  17. Page IH. Vasopressor action of extracts of plasma of normal dogs and dogs with experimentally produced hypertension. Proc Soc Exp Biol. 1937; 35: 112–116.
  18. Prinzmetal M, Friedman B, Oppenheimer ET. Failure to demonstrate pressor properties in extracts of blood from hypertensives. Proc Soc Exp Biol. 1938; 38: 493–494.
  19. Heymans C, Bouckaert JJ. Vasoconstrictor properties in blood of hypertensive dogs. Proc Soc Exp Biol. 1938; 39: 94–95.
  20. Solandt DJ, Massin R, Cowan CR. Hypertensive effect of blood from hypertensive dogs. Lancet. 1940; 1: 873–874.
  21. Houssay BA, Fasciolo JC. Secreción hipertensora del riñón isquemiado. Rev Soc Arg Biol. 1937; 13: 284–287.
  22. Fasciolo JC. Hipertensión arterial nefrógena: estudio experimental. Tesis Doct Med Ferrari, Hnos, Buenos Aires, 1939.
  23. Bouckaert JJ, Grimson KS, Heymans C. Increase of blood pressure by perfusion of the ischemic kidneys of hypertensive dogs. J Physiol. 1939; 96: 44–48.
  24. aquini AC, Braun-Menéndez E. Liberación de substancia vaso-constrictora en el riñón completamente isquemiado. Rev Soc Arg Biol. 1938; 14: 422–429.
  25. Houssay BA, Taquini AC. Acción vasoconstrictora de la sangre venosa del riñón isquemiado. Rev Soc Arg Biol. 1938; 14: 5–14.
  26. Taquini AC. Producción de sustancia vasoconstrictora renal en diversas circunstancias. Rev Soc Arg Biol. 1938; 14: 456–460.
  27. Fasciolo JC, Houssay BA, Taquini AC. The blood pressure–raising secretion of the ischemic kidney. J Physiol. 1938; 94: 281–293.
  28. Verney EB, Vogt M. An experimental investigation into hypertension of renal origin, with some observations on convulsive "uraemia". Q J Exp Physiol. 1938; 28: 253–259.
  29. Grimson KS. The onset of renal ischemia hypertension induced by readily adjustable renal artery clamps. J Physiol. 1939; 95: P45.
  30. Braun-Menéndez E, Fasciolo JC., Acción vasoconstrictora e hipertensora de la sangre venosa del riñón en isquemia incompleta aguda. Rev Soc Arg Biol. 1939; 15: 161–172.
  31. Braun-Menéndez E, Fasciolo JC. Mecanismo de la acción hipertensora de la sangre venosa del riñón en isquemia incompleta aguda. Rev Soc Arg Biol. 1939; 15: 401–410.
  32. Braun-Menéndez E, Fasciolo JC, Leloir LF, Muñoz JM. La sustancia hipertensora de la sangre del riñón isquemiado. Rev Soc Arg Biol. 1939; 15: 420–425.
  33. Leloir LF, Muñoz JM, Braun-Menéndez E, Fasciolo JC. La secreción de la renina y la formación de hipertensina. Rev Soc Arg Biol. 1940; 16: 75–80.
  34. Fasciolo JC, Leloir LF, Muñoz JM, Braun-Menéndez E. On the specificity of renin. Science. 1940; 92: 554–555.[Free Full Text]
  35. Page IH, McSwain B, Knapp GM, Andrus WD. The origin of renin activator. Amer J Physiol. 1941; 135: 214–222.
  36. Leloir LF, Muñoz JM, Taquini AC, Braun-Menéndez E, Fasciolo JC. La formación del angiotensinógeno. Rev Argent Cardiol. 1942; 9: 269–278.
  37. Braun-Menéndez E, Fasciolo JC, Leloir LF, Muñoz JM, Taquini AC. Hipertensión Arterial Nefrógena. Buenos Aires, Argentina: El Ateneo; 1943.
  38. Kohlstaedt KG, Helmer OM, Page IH, Activation of renin by blood colloids. Proc Soc Exp Biol Med. 1938; 39: 214–215.
  39. Page IH, Helmer OM. A crystalline pressor substance: angiotonin. Proc Center Soc Clin Invest. 1939; 12: 17.
  40. Page IH. On the nature of the pressor action of renin. J Exp Med. 1939; 70: 521–542.[Abstract]
  41. Page IH, Helmer OM. A crystalline pressor substance (angiotonin) resulting from the reaction between renin and renin-activator. J Exp Med. 1940; 71: 29–42.[Abstract]
  42. Page IH, Helmer OM, Plentl AA, Kohlstaedt KG, Corcoran AC. Suggested change in designation of "renin-activator" (hypertensinogen) to "renin-substrate ({alpha}2 globulin)". Science. 1943; 98: 153.[Free Full Text]
  43. Schwarz H, Bumpus FM, Page IH. Synthesis of a biologically active octapeptide similar to natural isoleucine angiotonin octapeptide. J Am Chem Soc. 1957; 5697–5703.
  44. Rittel W, Iselin B, Kappeler H, Riniker B, Schwyzer R. Synthese eines hochwirksamen hypertensin II-amids. Helv Chim Acta. 1957; 40: 614–616.
  45. Schwyzer R, Iselin B, Kappeler H, Riniker B, Rittel W, Zuber W. Synthese von hypertensin-peptiden: über die partielle hydrolyse von hypertensin-asp-ß-amiden zu den entsprechenden dicarbonsäuren: hypertensin II-analogue. Chimia. 1957; 11: 335–338.
  46. Page IH, McCubbin JW. Renal Hypertension. Chicago: Year Book Medical Publishers; 1968.
  47. Braun-Menéndez E, Paladini AC. Pressor polypeptides formed in vivo and in vitro as mediators of renal hypertension. Circulation. 1958; 27: 668–671.
  48. Taquini AC, Blaquier P,. Taquini AC Jr. Studies on the renal humoral mechanism of chronic experimental hypertension. Circulation. 1958; 27: 672–675.
  49. Braun-Menéndez E, Page IH. Suggested revision of nomenclature: angiotensin. Science. 1958; 127: 242.[Free Full Text]
  50. Taquini AC, Jr., Taquini AC. The renin-angiotensin system in hypertension. Am Heart J. 1961; 62: 558–564.[Medline] [Order article via Infotrieve]



This article has been cited by other articles:


Home page
 J. Am. Soc. Nephrol.Home page
S. C. Textor
Atherosclerotic Renal Artery Stenosis: Overtreated but Underrated?
J. Am. Soc. Nephrol., April 1, 2008; 19(4): 656 - 659.
[Abstract] [Full Text] [PDF]

Home page
 ANN INTERN MEDHome page
B. Glodny and D. E. Glodny
John Loesch, discoverer of renovascular hypertension, and Harry Goldblatt: two great pioneers in circulation research.
Ann Intern Med, February 21, 2006; 144(4): 286 - 295.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
V. D. Garovic and S. C. Textor
Renovascular Hypertension and Ischemic Nephropathy
Circulation, August 30, 2005; 112(9): 1362 - 1374.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
J. Ran, T. Hirano, and M. Adachi
Chronic ANG II infusion increases plasma triglyceride level by stimulating hepatic triglyceride production in rats
Am J Physiol Endocrinol Metab, November 1, 2004; 287(5): E955 - E961.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
I. H. Zucker
Brain Angiotensin II: New Insights Into Its Role in Sympathetic Regulation
Circ. Res., March 22, 2002; 90(5): 503 - 505.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Basso, N.
Right arrow Articles by Terragno, N. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Basso, N.
Right arrow Articles by Terragno, N. A.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH

Hypertension Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search
Copyright © 2001 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.