Inhibition of angiotensin I converting enzyme by venom peptides

Bakhle, Y.S.

doi:10.1111/j.1476-5381.1971.tb07176.x

Cited by 40 publications

(8 citation statements)

References 10 publications

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“…Other factors, such as absorption, distribution and metabolism, may also have been involved since SQ 20,475, the test peptide most active in a purified enzyme system (13), was less active in vivo than most of the longer-chain test peptides. Bakhle (14) has recently described studies with 3 of the venom peptides, SQ 20,475, SQ 20,881 and SQ 20,859, on the inhibition of angiatensinconverting enzyme in both a cell-free system and in perfused lungs of the guinea pig. Further evidence for specificity of this effect by SQ 20,881 on rat colon and guinea pig ileum has also been reported recently (15).…”

Section: ) After Im and Sc Administration Was Noted In Tests Vs Anmentioning

confidence: 98%

Inhibition of Pressor Effects of Angiotensin I and Augmentation of Depressor Effects of Bradykinin by Synthetic Peptides

Engel¹,

Schaeffer²,

Gold³

et al. 1972

Experimental Biology and Medicine

127

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In 1965 Ferreira (1) described the isolation and properties of bradykininpotentiating factor (BPF), a crude peptidic extract from the venom of the South American snake Bothrops jararaca. Three years later Bakhle ( 2 ) demonstrated that BPF also prevented the conversion of angiotensin I to angiotensin I1 in vitro and similar effects were seen in the perfused lung (3) and in intact animals (4).These dual activities of BPF were also exhibited by the first peptide isolated and identified from BPF, Pyr-Lys-Trp-Ala-Pro, originally called BPPS5, and herein referred to as SQ 20,475 ( 5 ) . At least 8 other peptides from the venom of B. jararaca have been isolated by Ferreira, Bartelt, and Greene (6) and by Ondetti et aZ. (7). The latter investigators also determined the amino acid sequence of 6 of these.We have investigated the dual activities in vivo of these 6 peptides and of SQ 20,475, all of which were synthesized by Ondetti et a2. (8). Struotures of the 7 test peptides are shown in Table I. Materials mad Methods. Male rats of the Sprague-Dawley strain, 250 to 450 g, were anesthetized with urethane, 1.5 g/kg, im, and then tracheotomized. The trachea and the arteries and veins mentioned below were cannulated with polyethylene tubing of appropriate size. Blood pressure was monitored from a femoral artery via a Statham P23GH pressure transducer coupled to a Beckman dynograph. The rats were given atropine sulfate (1 mg/kg, iv) and heparin (250 units,/ 1Preliminary reports of parts of this work have been presented a t the NXV Int. kg, iv). Each test peptide, except the less soluble SQ 20,475, was dissolved in physiological saline and injected stat iv? 0.1 ml/dose, followed by 0.4 ml saline "wash-in" within the next 30 sec. SQ 20,475 was first dissolved in 0.1 il' NaOH, adjusted with 0.1 N HCl to about pH 8.5 and injected stat iv, 0.1 ml/dose, "washed-in" with 0.4 ml saline. Other injections of some of the test peptides were made im or sc, 0.1 ml/injection. Rats employed in experiments involving angiotensions I and I1 received a continuous infusion of pentolinium bitartrate (0.2 mg/kg/min) into a femoral vein. In experiments involving bradykinin, pentolinium was not infused.[ Ile5] -angiotensin I was purchased from Schwartz/Mann, [ Am1, Val5] -angiotensin I1 was kindly supplied by Dr. A. J. Plummer of Ciba Pharmaceutical Company, and bradykinin was purchased from Cyclo Chemical and Nutritional Biochemicals. These challenge peptides were administered stat iv, 0.1 ml/dose, in physiological saline, followed by 0.4 ml saline wash-in, in all experiments.Blood pressure responses to control doses of the challenging agent(s), i.e., to 0.10 or 0.31 pg/kg of angiotensin I and to 0.031 or 0.10 pg/kg of angiotensin I1 or to 1, 3, or 10 pg/kg of bradykinin, were first determined for each rat. The test peptide was then administered and the challenging agent (s) were injected repeatedly at 2-to 10-min initervals. Not until responses to the challenges were approximately equal to those seen in the control period was another injection of th...

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Section: ) After Im and Sc Administration Was Noted In Tests Vs Anmentioning

confidence: 98%

Inhibition of Pressor Effects of Angiotensin I and Augmentation of Depressor Effects of Bradykinin by Synthetic Peptides

Engel¹,

Schaeffer²,

Gold³

et al. 1972

Experimental Biology and Medicine

127

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“…"1-13 There is considerable evidence that this enzyme also inactivates bradykinin. 14,16 Angiotensin converting enzyme inhibitor (CEI) is a nonapeptide originally isolated from the venom of Bothrops jararaca which has been shown to inhibit angiotensin converting enzyme in lung extract16 and in intact lungs in vivo. '7' 18 Collier, Robinson, and Vane'9 have demonstrated that CEI inhibits the pressor effect of infused angiotensin I in man with an estimated half-life of blockade of about three hours.…”

Section: Discussionmentioning

confidence: 99%

The role of the renin-angiotensin-aldosterone system in cardiovascular homeostasis in normal human subjects.

Sancho¹,

Ré²,

Burton³

et al. 1976

Circulation

175

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SUMMARY To examine the role of angiotensin II in the maintenance of blood pressure and the control of aldosterone secretion in man, eight normal subjects were studied on a tilt table in sodium replete and sodium depleted states prior to and subsequent to the intravenous infusion of an angiotensin converting enzyme inhibitor (CEI). In both the sodium replete or sodium depleted state, upright tilting resulted in an increase in heart rate and a narrowing of pulse pressure. None of the sodium replete or depleted subjects fainted. Tilting was accompanied by a rise in plasma renin activity with an associated rise in plasma aldosterone concentration. When converting enzyme inhibitor was administered, wbich blocked the generation of angiotensin II, sodium replete subjects were able to compensate for an upright tilt, despite the absence of angiotensin 11, without significant hemodynamic change when compared to control state. In sodium depleted subjects, after the administration of converting enzyme inhibitor, there was a sharp and significant decrease THE PRECISE ROLE of the renin-angiotensin system in the maintenance of blood pressure in normal human subjects remains unclear. The recent availability of effective competitive inhibitors of the angiotensin converting enzyme has permitted a critical examination of this question. Recent experiments in rats, rabbits, and trained conscious dogs' have demonstrated the importance of angiotensin II in the maintenance of blood pressure in the sodium depleted animal. In the experiments described here, the role of the renin-angiotensin system in the maintenance of blood pressure and in the regulation of aldosterone in relation to sodium depletion, diuretic administration, and posture was examined in normal human subjects. Methods Subjects Eight normal subjects (seven men, one woman), ranging in age from 19 to 27 years, were studied. All subjects were in in systolic and diastolic blood pressure associated with a significant rise in heart rate. All but one sodium depleted subject fainted within seven minutes. Both plasma aldosterone concentration and plasma renin activity rose on tilting in both sodium replete and sodium depleted subjects. After the administration of converting enzyme inhibitor, plasma aldosterone failed to rise in association with a rise in plasma renin activity. In supine subjects, after the administration of converting enzyme inhibitor, plasma renin activity rose but plasma aldosterone concentration fell. In sodium depleted subjects, after the administration of CEI, aldosterone fell to a level significantly lower than that in supine controls and to a level no different from the supine sodium replete subject. These results indicate that angiotensin II is essential for blood pressure maintenance in sodium depleted individuals, that angiotensin II exerts a direct feedback control on renin secretion, and that angiotensin It is the primary stimulus to aldosterone secretion in response to both sodium depletion and to posture.good health by history, had a normal physical ...

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“…TIVC constriction, although not a model of cardiac failure, simulates the hemodynamic consequences of impaired cardiac performance (10,11). By the use of the nonapeptide converting enzyme inhibitor (CEI) (12)(13)(14) which blocks the conversion of angiotensin I to the physiologically active pressor agent angiotensin II, we have been able to assess quantitatively the role of the RAA system in the regulation of systemic pressure during the development of congestive failure. We have also examined the role of the renin-angiotensin system in the regulation of plasma aldosterone levels, sodium excretion, and water balance.…”

Section: Introductionmentioning

confidence: 99%

The renin-angiotensin-aldosterone system in congestive failure in conscious dogs.

Watkins¹,

Burton²,

Haber³

et al. 1976

J. Clin. Invest.

293

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Inhibition of angiotensin I converting enzyme by venom peptides

Cited by 40 publications

References 10 publications

Inhibition of Pressor Effects of Angiotensin I and Augmentation of Depressor Effects of Bradykinin by Synthetic Peptides

Inhibition of Pressor Effects of Angiotensin I and Augmentation of Depressor Effects of Bradykinin by Synthetic Peptides

The role of the renin-angiotensin-aldosterone system in cardiovascular homeostasis in normal human subjects.

The renin-angiotensin-aldosterone system in congestive failure in conscious dogs.

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