Characterization of angiotensin receptors in rabbit isolated atria

1976 ◽  
Vol 54 (3) ◽  
pp. 229-237 ◽  
Author(s):  
F. Rioux ◽  
W. K. Park ◽  
D. Regoli
Keyword(s):  
Smooth Muscles ◽  
Rabbit Aorta ◽  
Angiotensin Receptors ◽  
Response Curves ◽  
Renin Substrate ◽  
Inotropic Effects ◽  
Isolated Atria ◽  
High Doses ◽  
The Right ◽  
Stimulation Of

Rabbit isolated left atria have been used to study the inotropic action of angiotensin II (ATII). The peptide is active at doses ranging from 1.0 × 10−9 to 2.8 × 10−6 M and its inotropic effect is not modified by sotalol, phentolamine, burimamide, and indomethacin. We therefore propose that this effect results from the stimulation of receptors specific for ATIIDose–response curves of ATII obtained in presence of increasing concentrations of 8-Gly-ATII are gradually displaced to the right, but high doses of the antagonist depressed the maximum contractions caused by ATII.pA2 value for 8-Gly-ATII in this preparation is similar to those observed in vascular and intestinal smooth muscles. Order of potency of analogues of ATII (2-, 3- and 5-Ala-ATII), acting as full agonists, but with reduced affinity, is similar to that found in rabbit aorta strips. It is therefore proposed that receptors for ATII in rabbit isolated left atria are pharmacologically similar to those present in vascular smooth muscles.Positive inotropic effects of angiotensin I, undecapeptide (1-11), dodecapeptide (1-12) and tetradecapeptide (1-14) renin substrate are antagonized by 8-Gly-ATII in a similar way as the effect of ATIIThis suggests that the action of these peptides is mainly due to stimulation of receptors for ATII. The contribution of myocardial converting enzyme to the action of these peptides is discussed.

scholarly journals Changes in the sensitivity to glucagon of lipolysis in adipocytes from pregnant and lactating rats

1988 ◽  
Vol 254 (3) ◽  
pp. 661-665 ◽  
Author(s):  
V A Zammit
Keyword(s):  
Adipose Tissue ◽  
The Other ◽  
High Concentration ◽  
Response Curves ◽  
Pregnant Rats ◽  
Adipose Tissue Lipolysis ◽  
The Right ◽  
Peak Lactation ◽  
Stimulation Of

1. Rates of lipolysis were measured at different concentrations of glucagon in adipocytes prepared from parametrial adipose tissue of fed or starved rats in different reproductive states. All experiments were performed in the presence of a high concentration of adenosine deaminase (1 unit/ml). 2. Maximal rates of lipolysis (elicited by 25 nM-glucagon in each instance) were higher in adipocytes from peak-lactating rats than those from pregnant animals in both the fed and starved states. 3. Of adipocytes from fed animals, those from peak-lactating rats were the most sensitive to glucagon, whereas those from late-pregnant and early-lactating rats were 1-2 orders of magnitude less sensitive. 4. Adipocytes from 24 h-starved rats showed a much smaller stimulation of lipolysis by glucagon, making the assessment of sensitivity difficult. Therefore, rates of lipolysis were also measured in the presence of a maximally anti-lipolytic dose of insulin. The presence of insulin did not alter the relative sensitivities to glucagon of adipocytes from fed animals in different reproductive states, although all dose-response curves were shifted to the right. When lipolysis in adipocytes from starved animals was measured in the presence of insulin, it became evident that starvation for 24 h markedly increased the sensitivity of adipocytes from late-pregnant rats to glucagon, but did not affect that of cells from animals in the other reproductive states. 5. It is concluded that the large changes in sensitivity to glucagon that occurred during the reproductive cycle may enable the modulation of adipose-tissue lipolysis in vivo to satisfy the different metabolic requirements of the animal in the transition from pregnancy to peak lactation.

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.

Studies on antihypertensive and antispasmodic activities of Andropogon muricatus Retz.This article is one of a selection of papers published in this special issue (part 1 of 2) on the Safety and Efficacy of Natural Health Products.

2007 ◽  
Vol 85 (9) ◽  
pp. 911-917 ◽  
Author(s):  
Anwar H. Gilani ◽  
Abdul J. Shah ◽  
Khalid H. Janbaz ◽  
Shahida P. Ahmed ◽  
Muhammad N. Ghayur
Keyword(s):  
Calcium Channel ◽  
Rabbit Aorta ◽  
Natural Health Products ◽  
Response Curves ◽  
Medicinal Uses ◽  
Health Products ◽  
Rabbit Jejunum ◽  
The Right

The aqueous-methanolic crude extract of Andropogon muricatus (Am.Cr) was investigated pharmacologically to determine some of its medicinal uses in cardiovascular and gastrointestinal disorders. A series of in vivo and in vitro studies were conducted to evaluate dose-dependent effects of Am.Cr on mean arterial pressure (MAP), cardiac and vascular contractions, and to further investigate the potential mechanism of action. Intravenous administration of Am.Cr (10–50 mg/kg) caused a fall (18%–56%) in MAP in normotensive rats under anesthesia. When tested in isolated guinea pig atria, Am.Cr (0.03–5.0 mg/mL) exhibited a cardiodepressant effect on the rate and force of spontaneous contractions. In isolated rabbit aorta, Am.Cr caused inhibition of K+ (80 mmol/L)-induced contractions at a lower concentration than of phenylephrine. In isolated rabbit jejunum preparations, Am.Cr (0.01–0.10 mg/mL) caused relaxation of spontaneous and high K+ (80 mmol/L)-induced contractions, suggesting that the spasmolytic effect is mediated possibly through calcium channel blockade (CCB). The CCB activity was confirmed when pretreatment of the tissue with Am.Cr (0.03–0.1 mg/mL) shifted the Ca2+ dose–response curves to the right, similar to that caused by verapamil. These data indicate that the blood pressure-lowering and spasmolytic effects of Am.Cr are mediated possibly through a calcium channel blocking activity. Phytochemical screening of Am.Cr revealed the presence of phenols, saponins, tannins, and terpenes, which may be responsible for the observed vasodilator, cardiodepressant, and antispasmodic activities. This study shows potential with respect to its medicinal use in cardiovascular and gut disorders.

Effects of endothelin on spontaneous contractions in lymph vessels

1999 ◽  
Vol 277 (2) ◽  
pp. H459-H466 ◽  
Author(s):  
Hiroshi Sakai ◽  
Fumitaka Ikomi ◽  
Toshio Ohhashi
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscles ◽  
Significant Inhibition ◽  
Lymphatic Endothelial Cells ◽  
Chronotropic Effect ◽  
Inotropic Effects ◽  
Mechanical Removal ◽  
Spontaneous Contractions ◽  
Positive Chronotropic Effect ◽  
Stimulation Of

A mode of action of endothelin (ET) on spontaneous contractions was investigated in ring preparations of isolated bovine mesenteric lymphatics. ET-1 at concentrations between 10−10 and 10−9 M caused a dose-dependent increase in the frequency of spontaneous contractions. The specific ETA-receptor antagonist BQ-123 (5 × 10−7 M) caused a significant inhibition of the ET-1-induced positive chronotropic effect in the ring preparations with and without the endothelium. Mechanical denudation of the lymphatic endothelial cells produced a significant potentiation of the ET-induced positive chronotropic effect. BQ-3020 (10−8–10−7M), a selective ETB-receptor agonist, induced dose dependently negative chronotropic and inotropic effects on the spontaneous contractions in the ring preparations with intact endothelium. Mechanical removal of the endothelium caused a significant reduction of the BQ-3020-induced negative chronotropic and inotropic effects. The ET-1-induced positive chronotropic effect was potentiated by pretreatment with N ω-nitro-l-arginine methyl ester (l-NAME) (10−5 M) but unaffected by aspirin (10−5 M). Additional treatment with l-arginine (10−4 M) completely reversed the l-NAME-mediated potentiation of the ET-induced chronotropic effect. These results suggest that stimulation of ETA receptors on the lymphatic smooth muscles causes a positive chronotropic effect on the spontaneous contractions, and stimulation of ETB receptors on the lymphatic endothelial cells induces a release of nitric oxide, which results in the chronotropic and inotropic effects on spontaneous contractions in isolated bovine mesenteric lymphatics.

Role of Endothelial K + Channels in NO-Dependent Vasorelaxant Responses to Acetylcholine in Rat Aorta.

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 698-698
Author(s):  
John Quilley ◽  
Yue Qiu
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Rat Aorta ◽  
Dose Response Curve ◽  
Response Curves ◽  
K Channels ◽  
Voltage Dependent ◽  
The Right ◽  
Stimulation Of

P30 Endothelium-dependent vasorelaxant responses to acetylcholine (Ach) in rat aorta are mediated solely by NO. Rings precontracted with U46619 were used to investigate the role of endothelial K + channels. Thus, any effect of K + channel inhibitors on Ach responses in the absence of an effect on those to nitroprusside (NP) can be attributed to interference with Ach-induced stimulation of NO. Vasorelaxant responses to Ach (log EC 50 -7.29M) were abolished by removal of the endothelium or inhibition of NO synthesis with nitroarginine (100μM) which potentiated responses to NP (log EC 50 -9.41M vs -8.47M for control). In the presence of TEA (10mM) to inhibit K + channels, the dose-response curve for Ach, but not NP, was shifted to the right (log EC 50 -6.06). Elevation of extracellular K + (25mM KCl)also shifted the dose-response curve for Ach to the right. Inhibitors of specific types of K + channels: BaCl 2 (30μM), apamin (100nM), glibenclamide (10μM), charybdotoxin (50nM) and iberiotoxin (100nM) were without effect on dose-response curves to either Ach or NP. However, the combination of apamin (100nM) and charybdotoxin (50nM) but not apamin plus iberiotoxin, reduced relaxant responses to Ach (log EC 50 -6.95M) without affecting those to NP.These results confirm that Ach-induced relaxation of rat aorta is mediated entirely by endothelium-derived NO, the release of which apparently involves hyperpolarization of the endothelium. This effect is dependent on activation of a K + channel that is blocked by a combination of apamin/charybdotoxin but neither agent alone, possibly indicating characteristics of both Ca 2+ - activated and voltage-dependent K + channels.

Characterization of receptors for angiotensin in the rat vas deferens

1979 ◽  
Vol 57 (4) ◽  
pp. 417-423 ◽  
Author(s):  
J. Magnan ◽  
D. Regoli
Keyword(s):  
Smooth Muscle ◽  
Vas Deferens ◽  
Proteolytic Enzymes ◽  
Rabbit Aorta ◽  
Rat Vas Deferens ◽  
Converting Enzyme ◽  
Response Curves ◽  
Sympathetic Nerve Stimulation ◽  
The Right

Experiments were performed in the rat vas deferens to characterize the receptor for angiotensin mediating the potentiation of the sympathetic nerve stimulation by this peptide. For this purpose we measured the order of potency of various angiotensins, the affinity of two specific and competitive antagonists, and we compared the effects of several angiotensins in tissues desensitized by angiotensin II.The potency of natural angiotensins follows the order: ATII > ATI > ATIII the relative potency of a few analogues which resist degradation by proteolytic enzymes as well as the potency of three L-Ala analogues of ATII show similar changes as those observed in other smooth muscle preparations (e.g. the rabbit aorta).Affinity of antagonists was evaluated by measuring pA2 and is higher for [Leu8]-ATII than for [des-Asp1, Leu8]-ATII. Both antagonists appear to be competitive since they displace the dose-response curves of ATII and ATIII to the right without changing the slope of the curves. Desensitization with ATII renders the tissues insensitive to ATIII and to other angiotensins without changing the response of the tissues to substance P.ATII does not modify the action of exogenous NA on nonstimulated tissues. ATI has no direct effect since its action is completely blocked in the presence of an inhibitor of the converting enzyme (SQ. 14225), while the responses of the vas deferens to ATII and substance P are unaltered.It is concluded that the receptor for ATII in the rat vas deferens is of the same type as the receptor mediating contraction of the rabbit aorta.

Dissociation constants (KA) and relative efficacies of sympathomimetic amines in isolated atria during hypothermia-induced supersensitivity

1983 ◽  
Vol 61 (6) ◽  
pp. 572-580 ◽  
Author(s):  
Kenneth J. Broadley ◽  
John H. McNeill
Keyword(s):  
Dose Response ◽  
Dissociation Constants ◽  
Response Curves ◽  
Isolated Atria ◽  
Adrenoceptor Agonists ◽  
Dose Response Curves ◽  
The Right ◽  
Tension Curves ◽  
Noradrenaline And Adrenaline ◽  
Right Atria

Hypothermia increases the sensitivity of isolated cardiac muscle to stimulation by β-adrenoceptor agonists. The purpose of this study was to determine pharmacologically whether this supersensitivity is associated with a change in the affinity of agonists for the receptor. The positive inotropic and chronotropic responses of guinea-pig paced left and spontaneously beating right atria were recorded. Cumulative dose–response curves to noradrenaline (or adrenaline) were compared with isoproterenol in each tissue. At 38 °C, the rate curves were to the left of the tension curves, with lower mean effective concentration (EC50) values. However, this difference was less for noradrenaline and adrenaline which were therefore tension selective relative to isoproterenol. Lowering the temperature to 25 °C induced supersensitivity, all dose–response curves being displaced to the left. In the presence of carbachol the curves were shifted to the right with depression of the maxima. Dissociation constants (KA) were calculated from plots of reciprocals of equiactive concentrations obtained before and in the presence of carbachol. KA values for rate and tension responses of each agonist were identical at 38 °C, indicating that the rate selectivity was not due to affinity differences. The efficacies (er) of noradrenaline and adrenaline were greater than isoproterenol for tension, but smaller for rate responses, which may explain their relative tension selectivity. At 25 °C the KA values of all agonists were reduced approximately 10-fold. Hypothermia-induced supersensitivity is therefore associated with an increase in affinity for the cardiac β-adrenoceptor.

Resting load regulates vascular sensitivity by a cytosolic Ca(2+)-insensitive mechanism

1995 ◽  
Vol 268 (6) ◽  
pp. C1332-C1341 ◽  
Author(s):  
Y. Miyagi ◽  
S. Kobayashi ◽  
J. Nishimura ◽  
M. Fukui ◽  
H. Kanaide
Keyword(s):  
Calcium Concentration ◽  
Smooth Muscles ◽  
Cytosolic Calcium ◽  
Vascular Smooth Muscles ◽  
Response Curves ◽  
Force Development ◽  
Optimal Load ◽  
High K ◽  
Vascular Sensitivity ◽  
The Right

The cellular mechanism underlying the regulation of the contraction of vascular smooth muscles by resting load is unknown. To determine the effects of changes in the resting load on vascular sensitivity to high K+ and to 9,11-dideoxy-11 alpha, 9 alpha-epoxy-methanoprostaglandin F2 alpha (U-46619), the force and cytosolic calcium concentration ([Ca2+]i) of arterial strips were recorded at resting loads of 200 (optimal load), 50, and 10 mg. A decrease in the resting load elicited a small decrease in the basal [Ca2+]i level without affecting the extent of maximal [Ca2+]i elevation induced by either stimulus. Through a decrease in the resting load, the concentration-response curves for the force development of high K+ or of U-46619 shifted to the right, whereas those for [Ca2+]i did not. We conclude that the basal [Ca2+]i level and the force development, but not the agonist-induced [Ca2+]i signals, of vascular smooth muscles depend on the resting load. We response that the resting load regulates the sensitivity of vascular smooth muscles, irrespective of types of stimuli, through a [Ca2+]i-insensitive mechanism.

Calcium and angiotensin tachyphylaxis in rat uterine smooth muscle

1975 ◽  
Vol 228 (5) ◽  
pp. 1423-1430 ◽  
Author(s):  
RJ Freer
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscles ◽  
Rabbit Aorta ◽  
Rat Uterus ◽  
Uterine Smooth Muscle ◽  
Normal Tissues ◽  
High Concentrations ◽  
The Relationship ◽  
Very High ◽  
Stimulation Of

Studies were carried out to investigate the relationship between extracellular Ca++ and the ability of a particular smooth muscle to develop tachyphylaxis to angiotensin II (AII). Stimulation of rat uterus by AII was found to be dependent on extracellular Ca++. Placing the tissue in 0 Ca++ completely blocked AII-induced contractions as did the presence of the "Ca++ antagonists" verapamil (10- minus 5M), SKF 525-A (10- MINUS 5M), tetracaine (10- minus 4M), Mn++ (8 times 10- minus 3M), or La-3+ (10- minus 3M). In addition, it is no longer possible to produce tachyphylaxis to AII in deplorazed rat uterus under conditions of pH and Ca++ concentration in which a normally polarized preparation would be unresponsive. Verapamil, on the other hand, was an even more effective antagonist of AII in depolarized preparations (ID50 of 10- minus 8M) than in normal tissues (ID50 of 2.0 times 10- minus 7M). Like the rat uterus, the smooth muscle of the guinea pig ileum also develops tachyphylaxis to AII, and the effect of this peptide was also blocked by 10- minus 5 M verapamil. Rabbit aorta, however, was found to be relatively resistant to both development of tachyphylaxis under conditions of low Ca++ and low pH and also to inhibition by even very high concentrations of verapamil (10- minus 4M). The results of these studies suggest that the Ca++ site involved in the tachyphylactic response to AII may be a physiologically important one in those smooth muscles in which movement of extracellular Ca++ contributes to the inward ion currents during excitation. Verapamil, however, appears to act at a common step in the excitation-contraction sequence in rat uterus. A working model of the interaction of AII with rat uterine smooth muscle is presented.

RELATIONSHIP BETWEEN ELEVATION OF CYCLIC-3∲,5∲-GMP (cGMP) AND AGGREGATE FORMATION IN HUMAN PLATELETS

1987 ◽  
Author(s):  
M Edgecombe ◽  
M C Scrutton ◽  
R Kerry
Keyword(s):  
Dose Response ◽  
Platelet Rich Plasma ◽  
Human Platelets ◽  
Light Transmittance ◽  
Aggregate Formation ◽  
Response Curves ◽  
Specific Radioimmunoassay ◽  
A Chain ◽  
The Right ◽  
Stimulation Of

Maximal 3- to 5-fold increases in platelet cGMP levels as measured by specific radioimmunoassay are observed on stimulation of aspirin-treated platelet-rich plasma with saturating doses of ADP, adrenaline, 5HT, PAF, thrombin, 9,11-epoxymethano-PGH2 (U44069), collagen, ristocetin and the Ca2+-ionophore ionomycin. The dose/response curves for the elevation in cGMP induced by these agents are either superimposable on, or lie to the right of, those describing the rate or extent of the aggregatory response as measured by an increase in light transmittance. The increase in cGMP induced by ADP is totally inhibited by addition of PGI2 or forskolin with dose/response relationships superimposable on those observed for inhibition of the aggregatory response. No increase in cGMP is observed if platelets are stimulated by PAF or ionomycin in an unstirred system or when aggregation induced by ADP is prevented by addition of a monoclonal antibody which recognises the glycoprotein IIb/IIIa complex.Addition of the fibrinogen γ-chain C-terminal decapeptide (γ402-411) or α-Chain tetrapeptide ARG-GLY-ASP-SER prevents aggregation and the increase in cGMP induced by PAF. The γ-chain decapeptide also completely prevents the increase in cGMP induced by ristocetin, but the a-chain tetrapeptide is ineffective in this respect. Both peptides inhibit to some extent aggregate formation induced by ristocetin.The data demonstrates a strong correlation between aggregate formaticfn and the increase in the platelet cGMP levels and support the previous postulate that platelet-platelet contact causes, activation of guanylate cyclase. No relationship is apparent between the effects of the various agents tested on cGMP levels and their known ability to increase cytosolic Ca2+ concentration. (Supported by SERC and Ciba-Geigy.)

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