The Purification of Hypertensin I

Skeggs, Leonard T.; Kahn, Joseph R.; Shumway, Norman P.

doi:10.1084/jem.100.4.363

Cited by 100 publications

(33 citation statements)

References 9 publications

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“…In 1958, the pressor substance was named angiotensin* 1954 Discovery of Ang I and Ang II, and ACE --Skeggs et al [18].…”

Section: 1940mentioning

confidence: 99%

“…The discovery of renin, as a hypertensive factor in extracts of rabbit kidney, was appreciated many years later when it was shown that it had an important role in the experimental models of hypertension ( Table 1). In 1956, Skeggs and coworkers [18] discovered ACE, an enzyme which converts Ang I to Ang II, and they published the amino acid sequence of Ang II. On the basis of collected information, the classic concept on the RAS came out: renin is released from renal juxtaglomerular cells into the blood where it converts angiotensinogen to Ang I.…”

Section: Formation Metabolism and Actions Of Angiotensinsmentioning

confidence: 99%

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Pharmacological, Immunological, and Gene Targeting of the Renin-Angiotensin System for Treatment of Cardiovascular Disease

Igić¹,

Behnia²

2007

CPD

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Effective blood pressure control with a large arsenal of conventional antihypertensive drugs, such as diuretics, beta-adrenergic blockers, and calcium channel blockers, significantly reduce the morbidity and mortality associated with cardiovascular disease. However, blood pressure control with these drugs does not reduce cardiovascular disease risks to the levels in normotensive persons. Only two drug classes that inhibit or antagonize portions of the renin-angiotensin system (RAS), angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor type-1 (AT(1) receptor) blockers, have protective and beneficial effects unrelated to the degree of blood pressure reduction. These drugs may prevent the blood pressure related functional and structural abnormalities of the cardiovascular system and reduce the end organ-damage. The first part of this review presents the components of the RAS, biological actions of angiotensin peptides, and the functions of the enzymes that generate and metabolize angiotensins, including the likely effect of manipulating them. Special attention is devoted to renin, ACE, ACE2, chymase, and neprilysin. The second part of this review presents the rationale for targeting the RAS, based on clinical studies of the ACE inhibitors and AT(1) receptor blockers. Finally, we present the investigational agents acting on the RAS that have a potential for clinical usage, and give the perspective of pharmacological, immunological and gene targeting of the RAS for treatment of cardiovascular disease.

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“…In 1958, the pressor substance was named angiotensin* 1954 Discovery of Ang I and Ang II, and ACE --Skeggs et al [18].…”

Section: 1940mentioning

confidence: 99%

Section: Formation Metabolism and Actions Of Angiotensinsmentioning

confidence: 99%

Pharmacological, Immunological, and Gene Targeting of the Renin-Angiotensin System for Treatment of Cardiovascular Disease

Igić¹,

Behnia²

2007

CPD

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“…It is the only known substrate for renin, and is cleaved at a position between 10 and 11 amino acids to generate angiotensin I (Ang I). Skeggs's group was the first to successfully purify Ang I and Ang II from horse plasma with large quantities of hog renin [3][4][5]. Subsequent studies by this same group characterized ACE, the enzyme which converts Ang I to Ang II [6].…”

Section: Introductionmentioning

confidence: 99%

The angiotensin II type 1 receptor and receptor-associated proteins

et al. 2001

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The mechanisms of regulation, activation and signal transduction of the angiotensin II (Ang II) type 1 (AT1) receptor have been studied extensively in the decade after its cloning. The AT1 receptor is a major component of the renin-angiotensin system (RAS). It mediates the classical biological actions of Ang II. Among the structures required for regulation and activation of the receptor, its carboxyl-terminal region plays crucial roles in receptor internalization, desensitization and phosphorylation. The mechanisms involved in heterotrimeric G-protein coupling to the receptor, activation of the downstream signaling pathway by G proteins and the Ang II signal transduction pathways leading to specific cellular responses are discussed. In addition, recent work on the identification and characterization of novel proteins associated with carboxyl-terminus of the AT1 receptor is presented. These novel proteins will advance our understanding of how the receptor is internalized and recycled as they provide molecular mechanisms for the activation and regulation of G-protein-coupled receptors.

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“…Landis et al, 3 "' using kidney extracts presumably containing reuin, noted no change in the skin temperature of the rabbit ear. Corcoran and Page, 20 using angiotonin, found no change in the skin temperature of the dog.…”

Section: Skin Flow and Resistancementioning

confidence: 99%

Effect of Angiotensin Infusion on Regional Blood Flow and Regional Vascular Resistance in the Rat

Mandel

Sapirstein

1962

Circulation Research

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"4 have been comprehensively reviewed by Page and Bumpus. 5 Although the literature is replete with information on its overall pressor properties and its effects on the cardiac output, the effects of angiotensin on regional blood flow and organ vascular resistance have not been adequately evaluated for most regions. Observations on the regional effects of angiotensin have been confined to a few organs or areas. As will be shown in the Discussion, the results are not always consistent in different preparations, and little information is available in the intact animal.A method developed in the Department of Physiology at Ohio State University 0 allows the measurement of the distribution of the cardiac output to all organs simultaneously in the intact animal. The present report is concerned with the application of this method to the determination of regional blood flow and regional vascular resistance in rats anesthetized with sodium pentobarbital and infused with varying doses of angiotensin. MethodsTwo hundred and eleven female rats of the Sprague-Dawloy strain which had been fasted for 18 hours were used in these studies. Of these, 75 (51 control, 24 experimental) were used in blood From the Department of Physiology, Ohio State Univevsity, Columbus, and Aerospace Medical Laboratory, Wright Patterson Air Force Base, Ohio.This work was supported by grants-in-aid from the American Heart Association and the Central Ohio Heart Association. Support was also received from Grunt H-4730 from the National Heart Institute, U. S. Public Health Service.Dr. Mandol is a Captain (MC) in the United States Air Force. The opinions expressed in this paper are those of the authors and do not necessarily represent the views of the United States Air Force.Received for publication November 27, 1961. pressure measurements; 38 (10 control, 2S expei'iniental) were employed in cardiac output measurements; regional flow distribution for all organs other than the brain was measvii'ed in 71 (22 control, 49 experimental), and cerebral flow fraction was measured in 102 (37 control, 65 experimental). Water wns allowed ad libitum. The animals weighed between 190 and 250 Gm. Sodium pentoharbital (40 mg./Kg., intraperitoneally) was used as the anesthetic. Angiotensin 0 was infused into the femoral vein by means of a Harvard infusion pump for 5 to 25 minutes at 0.05 ml./niin. of solution containing concentrations of angiotensin sufficient to yield 0.05, 0.1, 0.2, 0.3, 0.4, or 0.5 /i.g./Kg. body weight/min.Mean arterial pressures were measured from the femoral artery in heparinized rats with a mercury manometer connected to the artery by a 25-or 27-gauge needle. The same animals were also used for either the cardinc output or the regional flow determination. Cardiac outputs were measured by the indicator-dilution technique, using Rb 80 as the indicator. The rate of sample collection was 60/tnin. Because of the hemorrhage produced by the cardiac output determination, different animals were used for regional blood flow studies.Distribution of blood flo...

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The Purification of Hypertensin I

Cited by 100 publications

References 9 publications

Pharmacological, Immunological, and Gene Targeting of the Renin-Angiotensin System for Treatment of Cardiovascular Disease

Pharmacological, Immunological, and Gene Targeting of the Renin-Angiotensin System for Treatment of Cardiovascular Disease

The angiotensin II type 1 receptor and receptor-associated proteins

Effect of Angiotensin Infusion on Regional Blood Flow and Regional Vascular Resistance in the Rat

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