Adenosine participates in regulation of smooth muscle relaxation in aortas from rats with experimental hypothyroidism

The contribution of adenosine receptors was evaluated in vascular relaxation in experimental hypothyroidism. Hypothyroid aortic rings contracted less than normal controls with noradrenaline, phenylephrine, and KCl; the difference was maintained after incubation with 1,3-dipropyl-8-p-sulfophenylxanthine (an A1 and A2 adenosine receptor blocker). The vascular relaxation induced by acetylcholine or carbachol was similar in normal and hypothyroid aortic rings. However, adenosine, N6-cyclopentyladenosine (an A1 adenosine receptor analogue), and 5'-N-ethylcarbox amidoadenosine (an A2 and A3 adenosine analogue) induced vasodilation that was larger in hypothyroid than in normal aortas. Nω-nitro-L-arginine methyl ester shifted the dose-response curves of adenosine, N6-cyclopentyladenosine, or 5'-N-ethylcarboxamidoadenosine to the right in both normal and hypothyroid vessels. The blocker 1,3-dipropyl-8-p-sulfophenylxanthine significantly reduced adenosine-induced relaxation in the hypothyroid but not in the normal aortic vessels. These results suggest that in hypothyroid aortas, a larger adenosine-mediated vasodilation is observed probably due to an increase in receptor number or sensitivity.Key words: adenosine receptors, nitric oxide, hypothyroidism, smooth muscle, rat aorta.

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Adenosine receptors in smooth muscle: structure–activity studies and the question of adenylate cyclase involvement in control of relaxation

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y85-160 ◽

1985 ◽

Vol 63 (8) ◽

pp. 972-977 ◽

Cited By ~ 7

Author(s):

H. P. Baer ◽

R. Vriend

Keyword(s):

Smooth Muscle ◽

Adenylate Cyclase ◽

Adenosine Receptor ◽

Adenosine Receptors ◽

Muscle Relaxation ◽

Smooth Muscle Relaxation ◽

Structure Activity ◽

Rabbit Intestine ◽

Adenosine Derivatives

Structure–activity studies with a number of adenosine derivatives and analogs, measuring their relaxant effects in a variety of smooth muscle systems, were conducted in the hope of obtaining indications of the possible involvement of adenylate cyclase in their mechanism of action. While it was confirmed that a C6 aminofunction is of importance for agonist activity, several compounds, in particular the relatively potent N6-hydroxylaminopurine ribonucleoside, were not antagonized by 8-p-sulfophenyltheophylline, indicating that some nucleosides cause smooth muscle relaxation by a mechanism other than adenosine receptor stimulation. Nucleosides not bearing a C6 aminofunction were essentially inactive in rabbit intestine but showed weak relaxant effects in bovine coronary artery; this may indicate a difference between the adenosine receptor systems in these tissues and the intracellular mechanisms of relaxation. Comparing the relative potencies of compounds such as adenosine, 2-chloroadenosine, 5′-(N-ethylcarboxamido)adenosine, and (−)N6-(R-phenylisopropyl)adenosine, which have been used widely to classify adenylate cyclase-coupled adenosine receptors, no uniform pattern became apparent among different smooth muscle systems used in this study and reported in the recent literature. Thus, we conclude that a classification of smooth muscle adenosine receptors according to criteria established for cyclase-coupled receptors may be inappropriate or misleading, particularly with respect to implications of adenylate cyclase involvement in the relaxant effects of adenosine and related nucleosides.

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Acetylcholine-induced endothelium-dependent vascular smooth muscle relaxation in nitroglycerin-tolerant isolated rat aorta

Heart and Vessels ◽

10.1007/bf02058283 ◽

1991 ◽

Vol 6 (3) ◽

pp. 175-180 ◽

Cited By ~ 3

Author(s):

Atsushi Namiki ◽

Jo Aikawa ◽

Masao Moroi ◽

Kiyoshi Machii ◽

Nobuharu Akatsuka

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Muscle Relaxation ◽

Rat Aorta ◽

Smooth Muscle Relaxation ◽

Vascular Smooth Muscle Relaxation ◽

Isolated Rat

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Cellular Ca2+ monitored by aequorin in adenosine-mediated smooth muscle relaxation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1985.248.1.h109 ◽

1985 ◽

Vol 248 (1) ◽

pp. H109-H117 ◽

Cited By ~ 1

Author(s):

A. B. Bradley ◽

K. G. Morgan

Keyword(s):

Smooth Muscle ◽

Electrical Stimulation ◽

Muscle Relaxation ◽

Dose Dependence ◽

Ionized Calcium ◽

Smooth Muscle Relaxation ◽

Response Curves ◽

Light Responses ◽

Bioluminescent Protein ◽

High Concentrations

We studied the effect of adenosine on cytoplasmic ionized calcium-force relationships in vascular smooth muscle (VSM) and determined the dose dependence of the observed effects. The bioluminescent protein aequorin was used as an index of cytoplasmic ionized calcium and was chemically loaded into ferret portal vein strips. The VSM strips were contracted with 33 mM potassium (K+), 5 X 10(-6) M phenylephrine (PE), or electrical stimulation. Force and aequorin light, i.e., cytoplasmic ionized calcium, were simultaneously recorded. Adenosine pretreatment (3.7 X 10(-6) M) reduced both force and light responses in contractures with K+, PE, or electrical stimulation. In contrast, the addition of adenosine during PE or K+ contractions decreased force without a change in light. Dose-response curves for the effects of adenosine on K+ contractures indicated that at low doses adenosine decreases force and cytoplasmic ionized calcium but that at high concentrations (greater than 3.7 X 10(-6) M) adenosine increases light and apparently relaxes VSM by desensitizing the myofilaments to cytoplasmic ionized calcium.

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EVALUATION OF IN-VITRO VASORELAXANT EFFECT (POTENTIAL ANTIHYPERTENSIVE) OF KIGELIA AFRICANA FRUIT METHANOL EXTRACT ON POTASSIUM CHLORIDE AND PHENYLEPHRINE INDUCED TENSION IN WISTAR RAT AORTA

FUDMA Journal of Sciences ◽

10.33003/fjs-2020-0403-414 ◽

2020 ◽

Vol 4 (3) ◽

pp. 470-475

Author(s):

A. O. Isah ◽

M. Idu ◽

A. A. Abdulrahman ◽

F. Amaechina

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Potassium Chloride ◽

Methanol Extract ◽

Muscle Relaxation ◽

Rat Aorta ◽

Smooth Muscle Relaxation ◽

Organ Bath ◽

Vasorelaxant Effect

This research on Kigelia africana was conducted in order to ascertain its ability to relax excited vascular smooth muscle in rat aorta. Preliminary investigation on whether the plant exhibits antihypertensive property was done before the evaluation of in vitro vasorelaxant effect. The vasorelaxant activity was determined using in vitro method on rat aorta with the aid of perfusion apparatus with a detachable organ bath. The administration of potassium chloride (KCl) raised the tension from 1.0 to 1.31 indicating that the aorta got to its peak of contraction. At 10 and 20mg/kg, the tension dropped significantly, showing relaxation of the smooth muscle while at 5mg/kg, drop in tension was insignificant at p˂0.05. However, at some of the doses, towards the end of experiment, there was steady resurge in tension showing that the aorta resumed contraction. On the application of phenylephrine (PE), the tension rose to 1.18g. On administration of the extract, the tension dropped slightly showing mild vascular smooth muscle relaxation. From the results obtained, there was seeming similarity in the action of the K. africana compared to amlodipine/Ramipril in KCl and PE induced tension in aorta respectively. However, at 10 and 20mg/kg, a substantial decrease in tension was noted indicating that the extract action is dose dependent. Thus, from this in-vitro smooth muscle relaxation study in rats, the methanol extract of K. africana has depressant property that was likely expressed by enhancing the closing of voltage operated calcium channel and ACE inhibiting activity in KCl and Phenylephrine induced tension respectively.

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Differential effects of nitrovasodilators and nitric oxide on porcine tracheal and bronchial muscle in vitro

Journal of Applied Physiology ◽

10.1152/jappl.1994.77.3.1142 ◽

1994 ◽

Vol 77 (3) ◽

pp. 1142-1147 ◽

Cited By ~ 19

Author(s):

K. Stuart-Smith ◽

T. C. Bynoe ◽

K. S. Lindeman ◽

C. A. Hirshman

Keyword(s):

Nitric Oxide ◽

Methylene Blue ◽

Smooth Muscle ◽

Sodium Nitroprusside ◽

Airway Smooth Muscle ◽

Muscle Relaxation ◽

Ringer Solution ◽

Smooth Muscle Relaxation ◽

Response Curves

Nitrovasodilators and nitric oxide relax airway smooth muscle. The mechanism by which nitrovasodilators are thought to act is by release of nitric oxide, but the importance of nitric oxide in nitrovasodilator-induced airway smooth muscle relaxation is unclear. The aim of this study was to compare the relaxing effects of nitric oxide itself with those of nitrovasodilators in porcine tracheal muscle and intrapulmonary airways and to investigate the mechanisms involved. Strips of porcine tracheal smooth muscle, rings of bronchi, and strips of bronchi from the same animal were suspended in organ chambers in modified Krebs Ringer solution (95% O2–5% CO2, 37 degrees C). Tissues were contracted with carbachol, and concentration-response curves to nitric oxide, sodium nitroprusside, and SIN-1 (an active metabolite of molsidomine) were obtained. All tissues relaxed to sodium nitroprusside, SIN-1, and nitric oxide. The relaxation to nitric oxide but not to SIN-1 or sodium nitroprusside was inhibited by methylene blue. Tissues pretreated with methylene blue that failed to relax to nitric oxide were, however, relaxed by sodium nitroprusside. These results demonstrate that nitrovasodilators relax airways by a mechanism other than by or in addition to the release of nitric oxide.

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Persea Americana Seeds Cause Ileal Smooth Muscle Relaxation Via Stimulation of α-1 Adrenoceptors

Drug Research ◽

10.1055/a-1076-0703 ◽

2020 ◽

Vol 70 (02/03) ◽

pp. 107-111

Author(s):

Olayinka Ayotunde Oridupa ◽

Adedunke Omobolanle Oshinloye ◽

Ayobami Deborah Obisesan ◽

Opeyemi Mordiyah Olateju ◽

Victor Adedotun Adenuga

Keyword(s):

Smooth Muscle ◽

Muscle Relaxation ◽

Persea Americana ◽

Smooth Muscle Relaxation ◽

Drug Candidate ◽

Response Curves ◽

Rabbit Ileum ◽

Adrenergic Antagonist ◽

Food Absorption ◽

Reactivity Study

AbstractThe effect of methanol extract of P. americana seeds on isolated ileal smooth muscle was studied for isometric response using 10 adult rabbits of both sexes. Reactivity and agonist-antagonist responses of rabbit ileum to the extract were determined in this study. The affinity, effective concentration to give 50% response (EC50) and maximum response were calculated from the concentration response curves (CRC) obtained. The result for the reactivity study showed the seed extract of P. americana caused concentration dependent relaxation of isolated rabbit ileum with threshold responses at concentration of 1×10−9 mg/ml and 120 mg/ml respectively. The extract-antagonist study showed an upward and right shift in CRC in the presence of phenoxybenzamine, a non-selective adrenergic antagonist, with the EC50 increased from 5.01 mg/ml to 12.59 mg/ml and affinity decreased from 0.20 to 0.08. Extract-antagonist study also showed a right and upward shift in the CRC with a greater magnitude in the presence of prazosin, an α1-adrenergic antagonist, with EC50 increased from 0.32 mg/ml to 25.12 mg/ml and a consequential decrease in the affinity from 3.13 to 0.04. In the presence of propranolol, a β-adrenergic antagonist, a downward and left shift in the CRC was observed with the EC50 and PA2 remaining constant at 0.1 mg/ml and 10 respectively. P. americana concentration-dependently reduced or inhibited gastric motility, increasing transit time which is important for food absorption, thus a pro-nutritive and antispasmodic effect. The interaction with α1-adrenoceptors is beneficially in heart failure management. The plant can be developed as a drug candidate for management of hypertension.

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Comparison of vasoactive intestinal peptide and isoproterenol relaxant effects in isolated cat airways

Journal of Applied Physiology ◽

10.1152/jappl.1984.56.4.986 ◽

1984 ◽

Vol 56 (4) ◽

pp. 986-992 ◽

Cited By ~ 29

Author(s):

R. J. Altiere ◽

L. Diamond

Keyword(s):

Smooth Muscle ◽

Vasoactive Intestinal Peptide ◽

Muscle Relaxation ◽

Smooth Muscle Relaxation ◽

Response Curves ◽

Relaxation Responses ◽

Relaxation Curves ◽

Airway Tone ◽

Avian Pancreatic Polypeptide

Vasoactive intestinal peptide (VIP), an endogenous peptide found in mammalian tissues including the lung, is a potent relaxant of smooth muscle. In precontracted segments of cat trachea, hilar bronchus, and intrapulmonary bronchus, concentration-relaxation curves to VIP were compared with those produced by isoproterenol. VIP and isoproterenol were nearly equipotent in causing relaxation of extrapulmonary airways. A decreasing sensitivity to VIP was observed in progressively smaller airways, suggesting regional variation in VIP-induced responses. In contrast, tissues showed no regional differences in response to isoproterenol. Propranolol (10(-6) M), which antagonized relaxation responses to isoproterenol, had no effect on VIP concentration-response curves. Indomethacin (10(-5) M) completely prevented responses to exogenous arachidonic acid but did not inhibit VIP-induced relaxation. Avian pancreatic polypeptide, which has been reported to inhibit vasodilator responses to VIP in the cat, was unable to antagonize airway smooth muscle relaxation induced by VIP. These results demonstrate that VIP is a potent relaxant of cat tracheobronchial smooth muscle in vitro and that the relaxant effects of this peptide are not mediated through beta-adrenergic receptors or by prostaglandins. In view of previous reports on the localization of VIP immunoreactivity in nerves around airways in cat lung, results of the present study suggest that VIP may participate in the regulation of airway tone in this species.

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Properties of smooth muscle hyperpolarization and relaxation to K+ in the rat isolated mesenteric artery

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2001.280.6.h2424 ◽

2001 ◽

Vol 280 (6) ◽

pp. H2424-H2429 ◽

Cited By ~ 47

Author(s):

Kim A. Dora ◽

Christopher J. Garland

Keyword(s):

Smooth Muscle ◽

Mesenteric Artery ◽

Muscle Relaxation ◽

Relaxation Curve ◽

Mesenteric Arteries ◽

Muscle Membrane ◽

Smooth Muscle Relaxation ◽

Smooth Muscle Membrane ◽

Inner Diameter ◽

The Right

Smooth muscle membrane potential and tension in rat isolated small mesenteric arteries (inner diameter 100–200 μm) were measured simultaneously to investigate whether the intensity of smooth muscle stimulation and the endothelium influence responses to exogenous K+. Variable smooth muscle depolarization and contraction were stimulated by titration with 0.1–10 μM phenylephrine. Raising external K+ to 10.8 mM evoked correlated, sustained hyperpolarization and relaxation, both of which were inhibited as the smooth muscle depolarized and contracted to around −38 mV and 10 mN, respectively. At these higher levels of stimulation, raising the K+ concentration to 13.8 mM still hyperpolarized and relaxed the smooth muscle. Relaxation to endothelium-derived hyperpolarizing factor, released by ACh, was not altered by the level of stimulation. In endothelium-denuded arteries, the concentration-relaxation curve to K+ was shifted to the right but was not depressed. In denuded arteries, relaxation to K+ was unaffected by the extent of prior stimulation and was blocked with 0.1 mM ouabain but not with 30 μM Ba2+. The ability of K+ to stimulate simultaneous hyperpolarization and relaxation in the mesenteric artery is consistent with a role as an endothelium-derived hyperpolarizing factor activating inwardly rectifying K+ channels on the endothelium and Na+-K+-ATPase on the smooth muscle cells.

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