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.

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.

scholarly journals Possible Tracheal Relaxant and Antimicrobial Effects of the Essential Oil of Ethiopian Thyme Species (Thymus serrulatus Hochst. ex Benth.): A Multiple Mechanistic Approach

2021 ◽  
Vol 12 ◽  
Author(s):  
Najeeb Ur Rehman ◽  
Mohd Nazam Ansari ◽  
Tesfay Haile ◽  
Aman Karim ◽  
Khalil Y Abujheisha ◽  
...  
Keyword(s):  
Essential Oil ◽  
Guinea Pig ◽  
Diffusion Method ◽  
Zone Of Inhibition ◽  
Response Curves ◽  
Relaxant Effect ◽  
Antimicrobial Effects ◽  
Low Concentrations ◽  
Pde Inhibition ◽  
The Right

The genus Thymus is traditionally used for the treatment of hyperactive airways complaints. The purpose of the current study is to investigate the potential tracheal relaxant effect and possible mechanism(s) of the essential oil of Thymus serrulatus (TS Oil) in isolated guinea pig tracheal tissues. The essential oil was obtained from the fresh erial parts of Thymus serrulatus, and its phyto-components were identified by GC-MS analysis. Guinea pig tracheal preparations were used for testing the tracheal relaxant effect of TS Oil with the determination of the mechanism(s) involved in this relaxation. GC-MS findings reveal that terpenes, fragrance constituents, saponins, and higher fatty acids are present in TS Oil. In isolated guinea pig trachea, TS Oil inhibited carbachol (CCh, 1 µM) and K+ (80 mM)-induced contractions in a pattern similar to that of dicyclomine. TS Oil, at 0.3 mg/ml, shifted parallel CCh-curves towards the right, followed by a non-parallel shift at higher concentration (1 mg/ml), thus suppressing maximum response in the same manner as produced by dicyclomine. Pretreatment of tissues with TS Oil (1 and 3 mg/ml) also produced a rightward shift of Ca++ concentration-response curves (CRCs) in the same manner as caused by verapamil. Further, TS Oil at low concentrations (0.3 and 1 mg/ml) shifted isoprenaline-induced inhibitory CRCs towards the left and increased cAMP levels in isolated tracheal homogenates similar to papaverine, a phosphodiesterase (PDE) inhibitor. In the antimicrobial assay performed by the agar well diffusion method, TS Oil was found most active against Candida albicans and Staphylococcus aureus where the zone of inhibition measured was 28 mm. Additionally, there was little difference between standard strains of gram-positive and gram-negative bacteria. However, methicillin-resistant S. aureus (MRSA) showed a small zone of inhibition as compared to standard strains (22 mm). From these results, it can be concluded that the essential oil of T. serrulatus has the potential to produce antimicrobial effects while causing tracheal relaxation mediated possibly by anticholinergic effects, Ca++ channel blockade, and PDE inhibition whereas additional mechanism(s) cannot be ruled out.

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.

EFFECT OF ANGIOTENSIN ON THE RELEASE OF ACETYLCHOLINE FROM PREGANGLIONIC AND POSTGANGLIONIC NERVE ENDINGS

1967 ◽  
Vol 45 (2) ◽  
pp. 313-317 ◽  
Author(s):  
J. -C. Panisset
Keyword(s):  
Guinea Pig ◽  
Fold Increase ◽  
Guinea Pig Ileum ◽  
Cholinergic Mechanism ◽  
Cervical Ganglion ◽  
Release Of Acetylcholine ◽  
Stimulation Period ◽  
Effective Doses ◽  
The Right ◽  
Postganglionic Nerve

Angiotensin is known to stimulate the synaptic transmission of the cat superior ganglion and the contraction of the isolated guinea pig ileum; to determine whether these effects could be mediated by a cholinergic mechanism, both preparations were tested for the possible release of acetylcholine by angiotensin. The right cervical ganglion of 12 anesthetized cats was perfused with heparinized cat plasma, and the preganglionic sympathetic trunk was electrically stimulated supramaximally at 10-min intervals. After each stimulation, the acetylcholine content of the effluent was determined by bioassay. Angiotensin, injected intraarterially toward the ganglion in amounts ranging from 0.1 to 100 ng immediately before a stimulation period induced a 30 to 50% increase in acetylcholine output. Most effective doses ranged from 0.5 to 20 ng. Comparable experiments were carried out on coaxially stimulated strips of guinea pig ileum in Krebs solution. The addition of angiotensin, 1 ng/ml, was followed by a 4.3-fold increase in acetylcholine release during the period of contractile stimulation. From these two sets of data, it is concluded that angiotensin exerts a cholinergic action at the preganglionic level in the ganglion and at a postganglionic site in the ileum.

GABAB receptor antagonism by 7-MBFG, a benzo[b]furan analogue of baclofen, in central and peripheral tissues

1998 ◽  
Vol 76 (7-8) ◽  
pp. 798-801
Author(s):  
Jennifer Ong ◽  
David I Kerr ◽  
M'Hammed Ansar ◽  
Claude Vaccher ◽  
Pascal Berthelot
Keyword(s):  
Guinea Pig ◽  
Response Curve ◽  
Gabab Receptor ◽  
Guinea Pig Ileum ◽  
Butanoic Acid ◽  
Peripheral Tissues ◽  
Aromatic Character ◽  
Rat Neocortex ◽  
The Right ◽  
Concentration Response Curve

(R,S)-4-Amino-3-(7-methylbenzo[b]furan-2-yl)-butanoic acid (7-MBFG), a new benzofuran analogue of the GABAB receptor agonist baclofen, has been evaluated for pharmacological activity on GABAB receptors in the guinea-pig isolated ileum and rat neocortical slices. 7-MBFG (300 and 500 µM) reversibly antagonized the (R,S)-baclofen induced depression of cholinergic twitch contractions in the guinea-pig ileum and shifted the concentration-response curve for baclofen to the right, in a parallel manner, giving an apparent pA2 value of 3.7 ± 0.3. Likewise, 7-MBFG (300 and 500 µM) reversibly blocked the baclofen-induced suppression of spontaneous discharges, in rat neocortical slices maintained in Mg2+-free Krebs medium, and caused a rightward, parallel shift of the baclofen concentration-response curve, giving an apparent pA2 value of 4.1 ± 0.1. The compound 7-MBFG belongs to a novel, new class of antagonist at central and peripheral GABAB receptors, in which the antagonist properties reside in the pseudo-aromatic character of their 3-benzo[b]furan-2-yl substituents, and might provide useful leads for further development of GABAB receptor ligands.Key words: (R,S)-baclofen, 4-amino-3-(7-methylbenzo[b]furan-2-yl)-butanoic acid, GABAB receptor antagonist, rat neocortex, guinea-pig ileum.

BaCl2-induced contractions in the guinea pig ileum longitudinal muscle: role of presynaptic release of neurotransmitters and Ca2+ translocation in the postsynaptic membrane

1981 ◽  
Vol 59 (6) ◽  
pp. 541-547 ◽  
Author(s):  
John G. Clement
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Longitudinal Muscle ◽  
Postsynaptic Membrane ◽  
Muscle Membrane ◽  
Guinea Pig Ileum ◽  
Presynaptic Neuron ◽  
Smooth Muscle Membrane ◽  
Release Of Acetylcholine ◽  
The Right

Early studies indicated that the BaCl2-induced contractions in the guinea pig ileum longitudinal muscle strip (GPI-LMS) were, in part, neuronal in origin. However, recent studies have suggested that BaCl2-induced contractions were produced by an action directly on the smooth muscle membrane. The purpose of this study was to investigate the mechanism of the BaCl2 contractions in the GPI-LMS. Botulinum toxin (5 × 105 MLD/mL), which blocks the electrically induced release of acetylcholine (ACh), hemicholinium-3 (HC-3; 110 μM), which blocks ACh synthesis, tetrodotoxin (TTX; 60 nM), which blocks Na+ channels, black widow spider venom, which depletes the presynaptic neuron of neurotransmitter, and atropine (2.9 μM), a potent muscarinic antagonist, had no effect on the BaCl2 contractions. Desensitization of the GPI-LMS to substance P did not affect the BaCl2 contraction. In Ca2+-free buffer the BaCl2 dose–response curve was shifted to the right. In Ca2+-free solution the time to 50% inhibition of the contractile response to ACh (73 nM) and BaCl2 (1.16 mM) was 3.7 and 125 min, respectively. The D 600 IC50 for ACh and BaCl2 contractions was 220 and 130 nM, respectively. In Ca2+-free buffer either EGTA (0.53 mM) or D 600 (1 μM) were potent inhibitors of BaCl2 contractions. These results suggest that in the GPI-LMS the BaCl2 response is not mediated by a release of ACh (or substance P) because inhibitors of ACh release, synthesis, and receptors do not affect the responses. Also, the BaCl2 contraction is not due to activation of Na+ channels because TTX is without effect. The BaCl2-induced contraction appears to be mainly due to the movement of membrane bound Ca2+ through D 600 sensitive Ca2+ channels with extracellular Ca2+ and possible passage of Ba2+ ions intracellularly playing relatively minor roles.

Different pathways for Ca2+ mobilization by angiotensin II and carbachol in the circular muscle of the guinea-pig ileum

1999 ◽  
Vol 367 (1) ◽  
pp. 59-66 ◽  
Author(s):  
Suma I Shimuta ◽  
Antonio C.R Borges ◽  
Rogério N Prioste ◽  
Therezinha B Paiva
Keyword(s):  
Angiotensin Ii ◽  
Guinea Pig ◽  
Circular Muscle ◽  
Guinea Pig Ileum

Altered contractility of circular and longitudinal muscle in TNBS-inflamed guinea pig ileum

1997 ◽  
Vol 272 (5) ◽  
pp. G1258-G1267 ◽  
Author(s):  
J. P. Martinolle ◽  
R. Garcia-Villar ◽  
J. Fioramonti ◽  
L. Bueno
Keyword(s):  
Guinea Pig ◽  
Dose Range ◽  
Circular Muscle ◽  
Maximal Response ◽  
Guinea Pig Ileum ◽  
Trinitrobenzenesulfonic Acid ◽  
Response Curves ◽  
Contractile Responses ◽  
Guinea Pig Model

Intestinal motility disorders are often associated with gut inflammation. We evaluated, in vitro under isometric conditions, changes in contractility of longitudinal and circular muscle layers from guinea pig ileum after 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced ileitis. TNBS treatment did not modify length-active tension relationships for both muscle layers, whereas a significant increase in passive tension was observed in the circular muscle response to stretching. Moreover, in both control and inflamed strips at optimal stretch, concentration-response curves to KCl were similar for both layers. In contrast, contractile responses to receptor agonists were differentially altered in both layers in comparison with controls. Thus, in longitudinal strips from TNBS-treated ileum, there was a twofold increase in maximal response (Emax) induced by carbachol and histamine without modification of 50% effective concentration (EC50) values; responses to 5-hydroxytryptamine (5-HT) were not modified; both alpha 1- and alpha 2-adrenoceptor-mediated responses to epinephrine were abolished. In circular strips, inflammation did not affect the Emax induced by carbachol and histamine but led to increased EC50 values; Emax to 5-HT was reduced without change in EC50 values. Moreover, in the dose range used (0.1 nM to 0.1 mM), a maximal response to carbachol was not obtained in inflamed circular strips. The results indicate that in the guinea pig model of TNBS-induced ileitis, the in vitro contractile responses of circular and longitudinal smooth muscle to the stimulation of various receptors are differentially altered, whereas non-receptor-mediated contraction to KCl depolarization is not modified.

Sign in / Sign up

Export Citation Format

Share Document