The Pressor and Myotropic Effects and the Antagonistic Properties of Several Analogues of Angiotensin II

1972 ◽  
Vol 50 (2) ◽  
pp. 99-112 ◽  
Author(s):  
D. Regoli ◽  
W. K. Park
Keyword(s):  
Angiotensin Ii ◽  
Chemical Structure ◽  
Biological Activities ◽  
Unnatural Amino Acid ◽  
Intrinsic Activity ◽  
Rat Stomach ◽  
Response Curves ◽  
Isolated Organs ◽  
The Right ◽  
The Relationship

The substitution of an unnatural amino acid, 1-aminocyclopentanecarboxylic acid (Acpc), for each of the eight amino acids of angiotensin (AT) has been used to study the relationship between chemical structure and biological activities of angiotensin. The pressor and the myotropic activities of the various ATII derivatives have been tested on the rat blood pressure and on three isolated organs: rat isolated colon, rat stomach strip, and rabbit isolated kidney.The results indicate that 6-His and 8-Phe are essential for the activities of angiotensin II. Moreover, (8-Acpc)-ATII, but not (6-Acpc)-ATII, antagonizes the pressor and myotropic effects of ATII and ATI. αE and pD2 of all analogues have been estimated on the isolated rat stomach strip to evaluate intrinsic activity and affinity for the receptors. (1-, (2-, (3-, (4-, and (5-Acpc)-ATII have the same intrinsic activities as ATII, while those of (6-, (7-, and (8-Acpc)-ATII are much lower.Analogues of ATII substituted in position 8 antagonize specifically the myotropic and pressor effects of ATII and ATI. On the contrary, the effects of other smooth muscle stimulating agents (acetylcholine, 5-hydroxytryptamine, bradykinin, and vasopressin) are not modified.Log dose response curves of ATII and ATI are shifted to the right in the presence of antagonists, but remain parallel. The antagonism is rapidly reversible and may be competitive.

Pressor responses of rats to vasopressin: effect of sodium, angiotensin, and catecholamines

1983 ◽  
Vol 244 (2) ◽  
pp. H253-H258 ◽  
Author(s):  
M. Burnier ◽  
H. R. Brunner
Keyword(s):  
Angiotensin Ii ◽  
Sodium Intake ◽  
Pressor Response ◽  
Response Curves ◽  
Ether Anesthesia ◽  
Spontaneously Hypertensive ◽  
Lysine Vasopressin ◽  
Pressor Responses ◽  
Wistar Kyoto ◽  
The Right

The pressor response to lysine vasopressin was tested in groups of male Wistar, Brattleboro, Wistar-Kyoto, and spontaneously hypertensive rats. Moreover, the influence of sodium intake, angiotensin II, saralasin, captopril, norepinephrine, and isoproterenol on vasopressin pressor responses was evaluated. The right iliac artery and one or both femoral veins of the animals were catheterized under light ether anesthesia. The experiments were carried out following a 2-h stabilization period with the rats awake and semirestrained. Pressor responsiveness was evaluated acutely on the basis of dose-response curves (0.5-4 mU). In the Wistar rats, angiotensin II (10 and 30 ng/min) and isoproterenol (10 ng/min) markedly decreased the response to vasopressin, whereas variations in sodium intake and blood pressure per se did not seem to exert any influence. Norepinephrine (250 ng/min) slightly enhanced the pressor responsiveness to the smaller doses of lysine-vasopressin. Brattleboro rats with congenital diabetes insipidus were less sensitive to vasopressin than the other animals, and neither angiotensin II nor isoproterenol induced any change. In conclusion, the pressor responsiveness to vasopressin can vary considerably depending on several factors. These must be taken into account when evaluating the possible pressor role of vasopressin in experimental and clinical settings.

Myotropic affinities of angiotensin II and des-Asp1-angiotensin II in rabbit aorta and femoral artery by microassay

1979 ◽  
Vol 57 (11) ◽  
pp. 1256-1266 ◽  
Author(s):  
William H. Waugh ◽  
Theodore E. Bales
Keyword(s):  
Angiotensin Ii ◽  
Femoral Artery ◽  
Rabbit Aorta ◽  
Mass Action ◽  
Intrinsic Activity ◽  
Angiotensin Receptors ◽  
Response Curves ◽  
Contractile Responses ◽  
Increased Sensitivity ◽  
Dose Dependent

Dose-dependent isometric contractions to [Asp1,Ile5]-angiotensin II (AII) and des-Asp1-[Ile5]-angiotensin II (AIII) were obtained with 3-mm-wide rings of rabbit thoracic aorta and femoral artery in microbaths. A period of 2.5–3 h was required to obtain reproducible contractile responses of increased sensitivity. Contractions developed faster and they were much more forceful but less sustained in femoral arterial rings than in aortic rings. Noncumulative dose–response curves with AII and AIII were parallel and reached the same maximum. Peak contractile responses were linearly proportional to the receptor stimulation predicted from the mass action equation and the concept of intrinsic activity relating bath dosage of agonist to the number of myotropic receptors occupied by AII and by AIII. These findings validated measurement of the myotropic affinities of both tissues for AII and AIII by the obtained ED50 values. In 0.6-mL baths, developed with the use of a meshed screen for reoxygenation, the apparent affinities of aortic muscle for AII and AIII averaged 0.149 and 0.0030 nM, respectively. The mean affinities were much greater at 0.594 and 0.236 nM, respectively, in femoral arterial muscle. The myotropic affinity for AIII relative to that for AII averaged 2.26% in the aorta but 40.8% in the femoral artery. The apparent affinities were reduced and contractions less forceful in 0.24-mL baths without regassing. The results suggest that AII and AIII may stimulate the same angiotensin receptors in aorta and femoral artery and that the receptors may be different in structure or immediate environment in these two vascular tissues.

Acute effects of ethanol on baroreceptor reflex control of heart rate and on pressor and depressor responsiveness in rats

1987 ◽  
Vol 65 (5) ◽  
pp. 834-841 ◽  
Author(s):  
A-R. A. Abdel-Rahman ◽  
Roy Russ ◽  
J. A. Strickland ◽  
W. R. Wooles
Keyword(s):  
Heart Rate ◽  
Angiotensin Ii ◽  
Baroreflex Sensitivity ◽  
Pressor Response ◽  
Base Line ◽  
Response Curves ◽  
Baroreflex Control ◽  
Conscious Rats ◽  
Upward Shift ◽  
The Right

In rats anesthetized with α-chloralose, doses of 0.1, 0.5, and 1 g/kg of ethanol produced an upward shift of baroreflex curves constructed by plotting the heart rate response against mean arterial pressure following evoked rises in mean arterial pressures by phenylephrine or angiotensin II. Whereas the upward shift of baroreceptor curves may be related, at least in part, to a higher base-line heart rate after ethanol, the data showed that the 1 g/kg dose of ethanol significantly depressed baroreflex sensitivity, suggesting that higher doses of ethanol impair baroreflex-mediated bradycardia. The phenylephrine, but not the angiotensin II or the nitroprusside, dose–response curves were shifted to the right after ethanol, indicating a decreased pressor responsiveness and suggesting that ethanol may have α-adrenergic blocking activity. This effect was also obtained in conscious rats. That this effect was not influenced by changes in baroreflex sensitivity was supported by the finding that a similar shift of the phenylephrine pressor–response curve was obtained in bilaterally vagotomized and hexamethonium-treated rats. Whether this effect of ethanol on baroreflex control of heart rate was influenced by anesthesia was investigated in conscious rats; the 1 g/kg dose of ethanol that produced the most significant decrease in baroreflex sensitivity was used in these experiments. Ethanol was still able to significantly inhibit baroreflex sensitivity in conscious rats, but the upward shift of the baroreflex curve and the elevated base-line heart rate no longer occurred. On the other hand, none of the three doses of ethanol had any significant effect on baroreflex-mediated tachycardia (in response to nitroprusside-evoked hypotension). The data suggest that high doses of ethanol selectively inhibit baroreflex-mediated bradycardia and that ethanol has an α-blocking-like activity in conscious and anesthetized rats.

Specific desensitization (tachyphylaxis) of the guinea pig ileum to angiotensin II

1977 ◽  
Vol 232 (2) ◽  
pp. H223-H230 ◽  
Author(s):  
T. B. Paiva ◽  
G. B. Mendes ◽  
A. C. Paiva
Keyword(s):  
Angiotensin Ii ◽  
Guinea Pig ◽  
Calcium Binding ◽  
Tight Binding ◽  
Guinea Pig Ileum ◽  
Response Curves ◽  
A Value ◽  
Zero Order Kinetics ◽  
Rate Of Recovery ◽  
The Right

Tachyphylaxis to [Ile5]angiotensin II (angiotensin) in the isolated guinea pig ileum was found to be more severe when the Ca2+ concentration or the temperature of the medium were lowered, or when glucose was absent. Incubation with indomethacin or prostaglandin E2 did not affect the onset of tachyphylaxis or recovery from the tachyphylactic state. The angiotensin dose-response curves of tachyphylactic organs were shifted to the right, and the maximum responses were depressed in proportion to the conditioning doses of the hormone. The recovery from tachyphylaxis followed zero-order kinetics and was not affected by Ca2+ concentration or pH. The temperature dependence of the rate of recovery yielded a value of 14.6 kcal/mol for the activation energy in the physiological temperature range. It is concluded that tachyphylaxis results from the tight binding of angiotensin to superficial calcium-binding sites in the smooth muscle cell membrane. Recovery from tachyphylaxis appears to involve displacement of angiotensin by calcium in a process that is dependent on active transport.

Application of Drug–Receptor Theories to Angiotensin

1973 ◽  
Vol 51 (9) ◽  
pp. 665-672 ◽  
Author(s):  
F. Rioux ◽  
W. K. Park ◽  
D. Regoli
Keyword(s):  
New York ◽  
Smooth Muscle ◽  
Rabbit Aorta ◽  
Biologically Active ◽  
Mass Action ◽  
Intrinsic Activity ◽  
Rat Stomach ◽  
Response Curves ◽  
Threshold Phenomenon ◽  
Specific Receptors

The myotropic action of angiotensin II has been studied on two smooth muscle preparations: the strip of rat stomach and of rabbit thoracic aorta. Contractions evoked by angiotensin are not modified by atropine, methysergide, and diphenhydramine on the rat stomach or by phentolamine, methysergide, and diphenhydramine on the rabbit aorta. It appears that angiotensin acts directly on specific receptors and not through release of acetylcholine on the stomach or of noradrenaline on the aorta. Interference by intramural prostaglandins is excluded because angiotensin is equally active on tissues pretreated or not with indomethacin.Dose–response curves obtained with angiotensin on the two tissues are close to the theoretical curves predicted by the mass–action law. The relations stimulus effect is linear, indicating that the extent of the contraction is proportional to the number of receptors occupied by the agonist. No threshold phenomenon or spare receptor capacity could be demonstrated in either tissue. It is therefore concluded that the interaction of angiotensin with its specific receptors in the two smooth muscle preparations can be analyzed quantitatively with the occupation theory by applying the concepts of affinity and intrinsic activity as defined by Ariens in 1964. (Molecular pharmacology. Vol. 1. The mode of action of biologically active compounds. Academic Press, New York.)

Characteristics Of The Contractions Induced By Prostaglandin E2-Like Activity In The Rat Stomach Strip And By Thromboxane A2-Like Activity In The Rabbit Aorta And Mesenteric Artery

1981 ◽  
Author(s):  
F J Zijlstra ◽  
J E Vincent
Keyword(s):  
Angiotensin Ii ◽  
Mesenteric Artery ◽  
Thromboxane A2 ◽  
Rabbit Aorta ◽  
Prostaglandin E ◽  
Rat Stomach ◽  
Cascade System ◽  
Response Curves ◽  
Rabbit Mesenteric Artery

The dose-response curves obtained in the measurement of the prostaglandin E (PGE) and thromboxane-A2 (TxA2)-like activity using a cascade system cons isting of a rat stomach strip , a rabbit aorta strip and a mesenteric artery were determined. The following linear relat ionships were observed:log dose-activity for PGE2 and the stomach strip , do se-activity for angiotensin II (All) and the rabbit aorta, log dose-log activity for angiotensin II and the rabbit mesenteric artery.The do se-activity curves for All and TxA2 are different when the rabbit aorta is used whereas the log dose-log activity curves are much more similar for the rabbit mesenteric artery. Therefore, AI I can only be used as a reference substance in the last case. A comparison was made of the TxA2 like activity measured by bioassay and the TxB2 determined by a radioimmunoassay in platelets after aggregation. The curves were parallel when the TxA2 like activity was measured with the mesenteric artery.The different contractile characteristics of these organs should be taken into account in the determination of the PGE2 like and TxA2 like activity with these tests.

Competitive antagonism of pressor responses to angiotensin II and angiotensin III by the angiotensin II-1 receptor ligand losartan

1992 ◽  
Vol 70 (5) ◽  
pp. 716-719 ◽  
Author(s):  
Aly Abdelrahman ◽  
Catherine C. Y. Pang
Keyword(s):  
Angiotensin Ii ◽  
Dose Response ◽  
Dissociation Constants ◽  
Ang Ii ◽  
Receptor Ligands ◽  
Response Curves ◽  
Competitive Antagonism ◽  
Angiotensin Iii ◽  
Dose Response Curves ◽  
The Right

Losartan (DuP 753) and PD123177 are nonpeptide angiotensin (ANG) receptor ligands for subtypes of ANG II receptors ANG II-1 and ANG II-2, respectively. We examined the effects of losartan and PD123177 on dose – mean arterial pressure (MAP) response curves for ANG II and ANG III in eight groups (n = 6 each) of conscious rats. Saline (0.9% NaCl), losartan (1 × 10−6 and 9 × 10−6 mol/kg), and PD123177 (2 × 10−5 mol/kg) were i.v. bolus injected 15 min before the construction of ANG II dose–response curves in groups I, II, III, and IV, respectively. Groups V–VIII were treated similarly to I–IV except that ANG III was given in place of ANG II. Losartan dose dependently shifted the dose–response curves of ANG II and ANG III to the right with similar dissociation constants (−log KI of 6.6 ± 0.7 and 6.6 ± 0.1 mol/kg, respectively) and no change in the maxima. PD123177 affected neither maximum MAP nor ED50 values for ANG II or ANG III. Our results show that losartan but not PD123177 is a competitive antagonist of the MAP effects of ANG II and ANG III.Key words: nonpeptide angiotensin receptor antagonist, angiotensin II, angiotensin III, blood pressure, losartan.

Ridogrel Inhibits Systemic and Renal Formation of Thromboxane A2 and Antagonizes Platelet Thromboxane A2/Prostaglandin Endoperoxide Receptors upon Chronic Administration to Man

1992 ◽  
Vol 68 (02) ◽  
pp. 214-220 ◽  
Author(s):  
C Weber ◽  
J R Beetens ◽  
F Tegtmeier ◽  
P Van Rooy ◽  
E Vercammen ◽  
...  
Keyword(s):  
Uric Acid ◽  
Potent Inhibitor ◽  
Ex Vivo ◽  
Thromboxane A2 ◽  
Chronic Administration ◽  
Response Curves ◽  
Clinically Significant ◽  
Synthase Inhibitor ◽  
The Right ◽  
Steady State Plasma Level

SummaryThe effects of ridogrel, a dual thromboxane A2 (TXA2) synthase inhibitor and TXA2/prostaglandin (PG) endoperoxide receptor antagonist, on systemic and renal production of prostaglandins and on platelet TXA2/PG endoperoxide receptors was evaluated upon chronic administration (300 mg b. i. d. orally, for 8 and 29 days) to man. Such a medication with ridogrel inhibits the systemic as well as the renal production of TXA2 as measured by the urinary excretion of 2,3-dinor-TXB2 and TXB2 respectively without inducing significant changes in systemic or renal PGI2 production. Simultaneously with the latter effects, the production of TXB2 by spontaneously coagulated whole blood ex vivo is inhibited (>99%) while that of PGE2 and PGF2α is largely increased. Administration of ridogrel causes a three- to five-fold shift to the right of concentration-response curves for U46619 in eliciting platelet aggregation; no tachyphylaxis is observed after 29 days of treatment in this respect. Apart from a reduction of serum uric acid levels with a concomitant increase in urinary uric acid excretion during the first days of treatment, no clinically significant changes in hematological, biochemical, hemodynamic and coagulation parameters occur during the 8 days or 29 days study. The study demonstrates that ridogrel is a potent inhibitor of the systemic as well as renal TXA2 synthase and an antagonist of platelet TXA2/PG endoperoxide receptor in man, covering full activity during 24 h at steady-state plasma level conditions without tachyphylaxis during 29 days of medication. The compound is well tolerated, at least during 1 month of administration.

Tanggung Jawab Hukum Penilai Publik terhadap Laporan Penilaian Kegiatan Pengadaan Tanah bagi Pembangunan untuk Kepentingan Umum (Studi Atas Kantor Jasa Penilai Publik Toto Suharto)

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Gagah Yaumiyya Riyoprakoso ◽  
AM Hasan Ali ◽  
Fitriyani Zein
Keyword(s):  
Future Development ◽  
Public Interest ◽  
Legal Responsibility ◽  
Legal Research ◽  
The Public ◽  
The Government ◽  
Conducting Research ◽  
The Right ◽  
The Relationship ◽  
Systematic Explanation

This study is based on the legal responsibility of the assessment of public appraisal reports they make in land procurement activities for development in the public interest. Public assessment is obliged to always be accountable for their assessment. The type of research found in this thesis is a type of normative legal research with the right-hand of the statue approach and case approach. Normative legal research is a study that provides systematic explanation of rules governing a certain legal category, analyzing the relationship between regulations explaining areas of difficulty and possibly predicting future development. . After conducting research, researchers found that one of the causes that made the dispute was a lack of communication conducted between the Government and the landlord. In deliberation which should be the place where the parties find the meeting point between the parties on the magnitude of the damages that will be given, in the field is often used only for the delivery of the assessment of the compensation that has been done.

Rancangan Sistem Pengukuran Kinerja Berbasis Human Resource Scorecard Pada Universitas Muhammadiyah Luwuk

2020 ◽  
Vol 10 (1) ◽  
pp. 63-71
Author(s):  
Nurhaeda Abbas ◽  
Anggraini Sukmawati ◽  
Muhammad Syamsun
Keyword(s):  
Performance Measurement ◽  
Human Resource ◽  
Performance Measurement System ◽  
Group Discussions ◽  
Strategic Objectives ◽  
Depth Interview ◽  
And Performance ◽  
The Right ◽  
Hierarchy Process ◽  
The Relationship

Today the performance measurement of Muhammadiyah Luwuk uUniversity’s performance has not formulated yet based on University’s vision and mission. It will affect the strategic steps needed and performance improvement efforts in the future.  Human resource scorecard is the right system to be applied in Muhammadiyah Luwuk University. The purpose of this study is to designed a performance measurement system at Muhammadiyah Luwuk University using the Human Resource Scorecard with four perspectives: stakeholder, academic management and kemuhammadiyaan, operational and innovation, as well as and learning. Data was analyzed by analytical hierarchy process method. This research was conducted by distributing questionnaires, focus group discussions and in-depth interview with stakeholders at Muhammadiyah Luwuk University. The results showed that there were 14 strategic objectives and 33 key performance indicators to be achieved by the priority objectives, which are: empowerment and development of faculty, increased administrative process quality, improved sound budget performance and, improvement of the relationship with stakeholders.

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