Ketamine potentiates catecholamine responses of vascular smooth muscle by inhibition of extraneuronal uptake

1981 ◽  
Vol 59 (6) ◽  
pp. 520-527 ◽  
Author(s):  
Paul M. Lundy ◽  
Robert Frew
Keyword(s):  
Smooth Muscles ◽  
Rabbit Aorta ◽  
Extraneuronal Uptake ◽  
Neuronal Uptake ◽  
Vascular Smooth Muscles ◽  
Comt Inhibitors ◽  
Relaxant Effect ◽  
17Β Estradiol ◽  
Uptake Studies ◽  
6 Hydroxydopamine

Effects of ketamine on responses to sympathomimetic amines were studied using isolated aortic and pulmonary artery strips from the rabbit. Ketamine (1.1 × 10−5 to 3.7 × 10−4 M) potentiated adrenaline-contracted strips. Potentiation was not impaired in tissues from animals pretreated with reserpine, with 6-hydroxydopamine, or in tissues pretreated with cocaine. Pretreatment of the strips with the catechol O-methyltransferase (COMT) inhibitors tropolone or pyrogallol or the inhibitor of extraneuronal uptake 17β-estradiol blocked the potentiation by ketamine; in addition, potentiation by the COMT and extraneuronal uptake inhibitors was abolished or greatly reduced by ketamine. In rabbit aorta, ketamine potentiated responses to the catecholamines (adrenaline > nordefrine > noradrenaline) but not to the noneatecholamines phenylephrine, methoxamine, and synephrine; instead a slight relaxant effect was observed. Ketamine potentiated, whereas cocaine inhibited, responses to tyramine. Experiments using the technique of oil immersion demonstrated that ketamine reduced the rate at which aortic strips inactivate adrenaline even when monoamine oxidase (MAO) and neuronal uptake processes were fully inhibited. Uptake studies showed that ketamine and 17β-estradiol reduced extraneuronal accumulation of [3H]adrenaline in aortic strips. We conclude that ketamine is an inhibitor of extraneuronal uptake in the vascular smooth muscles studied and the importance of this mechanism in producing its known cardiovascular effect is discussed.

Effects of kinins on isolated blood vessels. Role of endothelium

1982 ◽  
Vol 60 (12) ◽  
pp. 1580-1583 ◽  
Author(s):  
D. Regoli ◽  
J. Mizrahi ◽  
P. D'Orléans-Juste ◽  
S. Caranikas
Keyword(s):  
Arachidonic Acid ◽  
Carotid Artery ◽  
Common Carotid Artery ◽  
Smooth Muscles ◽  
Rabbit Aorta ◽  
Arachidonic Acid Metabolism ◽  
Arachidonic Acid Cascade ◽  
Vascular Smooth Muscles ◽  
Acid Metabolites

Bradykinin (BK) and des-Arg9-BK were used to determine whether the stimulatory and inhibitory actions of the kinins in various isolated vessels require the presence of endothelium and may be mediated by arachidonic acid metabolites. It was found that the presence of intact endothelium is required only for the relaxation of the dog common carotid artery in response to bradykinin. Stimulatory actions of both BK and des-Arg9-BK in arterial (rabbit aorta) and venous (rabbit jugular and mesenteric vein) smooth muscle do not require the presence of endothelium. Inhibition of the arachidonic acid cascade at various levels affects the relaxing action of acetylcholine (rabbit aorta and dog common carotid artery) while being inactive against both the relaxing (dog common carotid artery) and contractile actions (rabbit aorta, rabbit jugular and mesenteric veins) of bradykinin and des-Arg9-BK. Inhibitors of the arachidonic acid cascade also do not affect the inhibitory action of isopropylnoradrenaline on the rabbit aorta. The present results indicate that stimulant actions of kinins in isolated vascular smooth muscles do not require the presence of endothelium. Endothelium is required for the inhibitory actions of acetylcholine and bradykinin but not for that of isopropylnoradrenaline on the dog carotid artery. Moreover, the inhibition of arachidonic acid metabolism only affects the response of isolated vessels to acetylcholine. The present results suggest that several mechanisms may be involved in the inhibition of vascular tone by vasodilators.

Inhibition of neuronal noradrenaline uptake by angiotensin II in the rat mesentery

1979 ◽  
Vol 57 (12) ◽  
pp. 1443-1447 ◽  
Author(s):  
Edwin K. Jackson ◽  
William B. Campbell
Keyword(s):  
Angiotensin Ii ◽  
Extraneuronal Uptake ◽  
Neuronal Uptake ◽  
Appreciable Effect ◽  
Noradrenaline Uptake ◽  
Similar Extent ◽  
Rat Mesentery ◽  
Uptake Of Noradrenaline ◽  
6 Hydroxydopamine ◽  
Uptake Blockers

In the isolated perfused rat mesentery, angiotensin II (3 × 10−9 M) in subpressor doses enhanced the vasoconstrictor responses to noradrenaline by 9.6 ± 1.4 mmHg. However, in mesenteries obtained from rats chemically sympathectomized with 6-hydroxydopamine, angiotensin II was without effect. Treatment of mesenteries with the noradrenaline neuronal uptake blockers desmethylimipramine (10−10 M), protriptyline (10−10 M), or cocaine (10−6 M) potentiated responses to noradrenaline by 3.8 ± 0.84, 3.7 ± 0.67, and 5.5 ± 0.26 mmHg, respectively. Angiotensin II alone or in combination with either desmethylimipramine, protriptyline, or cocaine potentiated the noradrenaline responses to a similar extent. On the other hand, corticosterone (1.5 × 10−6 M), an extraneuronal uptake blocker, enhanced noradrenaline responses by 4.3 ± 1.4 mmHg, and this enhancement was additive with the potentiation produced by cocaine and (or) angiotensin II. We conclude that angiotensin II in subpressor doses acts presynaptically to block selectively the neuronal uptake of noradrenaline without any appreciable effect on extraneuronal uptake.

Ketamine: evidence of tissue specific inhibition of neuronal and extraneuronal catecholamine uptake processes

1985 ◽  
Vol 63 (4) ◽  
pp. 298-303 ◽  
Author(s):  
Paul M. Lundy ◽  
Sharunas Gverzdys ◽  
Robert Frew
Keyword(s):  
Mechanism Of Action ◽  
Rabbit Aorta ◽  
Adrenergic Innervation ◽  
Extraneuronal Uptake ◽  
Specific Inhibition ◽  
Chemical Sympathectomy ◽  
Rat Anococcygeus Muscle ◽  
Extraneuronal Catecholamine Uptake ◽  
6 Hydroxydopamine

Ketamine (1.1 × 10−5 to 3.7 × 10−4 M) potentiated catecholamine responses of rat anococcygeus muscle and rabbit aorta in vitro. In the anococcygeus, potentiation was abolished by cocaine (2.9 × 10−5 M) pretreatment or by chemical sympathectomy using 6-hydroxydopamine (6-OHDA), but was unaffected by pretreatment with the extraneuronal uptake inhibitor cortisol (8.3 × 10−5 M), or the catechol-O-methyltransferase inhibitor tropolone (2.4 × 10−4 M). The action of ketamine mimicked the potentiating effect of cocaine on tyramine responses. In contrast, the potentiation by ketamine in rabbit aorta was unaffected by cocaine or 6-OHDA but was abolished by cortisol or tropolone; and ketamine potentiated tyramine responses, whereas cocaine inhibited them. Thus the mechanism of action by which ketamine produces potentiation of catecholamines in these two tissues is completely different. These results suggest that ketamine has the unusual ability to block neuronal and extraneuronal uptake and that the predominating mechanism will depend on the type of tissue examined and the morphology of its adrenergic innervation.

scholarly journals Effect of protamine sulfate on the isolated mesenteric arteries of normotensive and spontaneously hypertensive rats

2008 ◽  
Vol 60 (2) ◽  
pp. 163-168 ◽  
Author(s):  
Zorana Orescanin-Dusic ◽  
S. Milovanovic ◽  
M. Spasic ◽  
R. Radojicic ◽  
D. Blagojevic
Keyword(s):  
Significant Role ◽  
Spontaneously Hypertensive Rats ◽  
Smooth Muscles ◽  
Relaxation Effect ◽  
Protamine Sulfate ◽  
Mesenteric Arteries ◽  
Vascular Smooth Muscles ◽  
Hypertensive Rats ◽  
Relaxant Effect ◽  
Spontaneously Hypertensive

We tested the relaxant effect of increased protamine sulfate (PS) amounts (10, 20, 50, 100 and 150 ?g/ml) on the isolated mesenteric arteries of normotensive and spontaneously hypertensive (SH) rats, with or without endothelium. PS caused concentration-dependent relaxation of isolated mesenteric arteries in both types of rats. The relaxation effect of PS was lower in SH rats than in normotensive ones. Our results indicate that the vascular smooth muscles play a significant role in PS-mediated relaxation.

Role of the N-terminal Amino Acid for the Biological Activities of Angiotensin and Inhibitory Analogues

1974 ◽  
Vol 52 (1) ◽  
pp. 39-49 ◽  
Author(s):  
D. Regoli ◽  
F. Rioux ◽  
W. K. Park ◽  
C. Choi
Keyword(s):  
Smooth Muscles ◽  
Rabbit Aorta ◽  
Intrinsic Activity ◽  
Vascular Smooth Muscles ◽  
Terminal Amino Acid ◽  
Duration Of Action ◽  
Metabolic Degradation ◽  
Terminal Amino

Aspartic acid was replaced in position 1 of angiotensin II (ATII) with several amino acids, to assess the possible influence of the N-terminal amino acid for (a) the intrinsic activity, (b) the affinity, and (c) the metabolic degradation of agonist analogues of ATII. Some of the substitutions in position 1 were used in combination with replacement of Phe by Gly or Leu in position 8, to obtain the corresponding antagonist.The compounds were tested in vivo (rat blood pressure) and in two in vitro preparations (rat stomach and rabbit aorta strips). The oil immersion technique, described by Kalsner and Nickerson (1968) (Can. J. Physiol. Pharmacol. 46, 719–730), was used to study the disposition of the peptides by vascular smooth muscles (rabbit aorta strips). Degradation of the peptides by purified aminopeptidases was evaluated in vitro by measuring the fragments on paper chromatography. Potency of antagonists was estimated in vivo (ID50) and in vitro (pA2 values): duration of action was established by infusing the inhibitors intravenously into anesthetized rats and testing the effect of standard doses of angiotensin before and after.The results indicate that replacement of Asp with other amino acids does not influence the intrinsic activity, but can either increase or decrease the affinity in vitro or the potency in vivo. 1-Sar-ATII, and 1-D-Ala-ATII are more potent and longer acting than 1-Asp-ATII on isolated intestinal and vascular smooth muscles, but not in vivo. On the contrary, 1-β-Asp-ATII and 1-β-D-Asp-ATII are more potent than 1-Asp-ATIIin vivo, but not on rabbit aorta strips. Rate of relaxation of rabbit aorta strips suspended in oil, after contraction with submaximal doses of several analogues of ATII, are significantly slower than relaxation after 1-Asn2-ATII and 1-Asp-ATII. A close parallelism between the diminution of the relaxation rate in oil and the degradation by aminopeptideses in vitro was observed, suggesting that metabolic degradation may be the major factor determining relaxation of rabbit aorta in oil after contraction with one of these peptides. Potencies of antagonists in vivo and in vitro are increased by replacing Asp with Sar. Substitution of Asp with β-Asp or β-D-Asp brings about a slight increase of potency in vivo but not in vitro. It appears that firm binding and prolonged occupation of receptors by sarcosyl derivatives are the primary factors contributing to increase the potency and to prolong the duration of action of antagonists, while prevention or reduction of metabolic breakdown by aminopeptidases is much less efficient.

Differentiation of mechanisms for mobilization of calcium in smooth muscle

1987 ◽  
Vol 65 (4) ◽  
pp. 724-728 ◽  
Author(s):  
George B. Weiss ◽  
Hideaki Karaki ◽  
Kazuyasu Murakami
Keyword(s):  
Smooth Muscle ◽  
Rate Coefficient ◽  
Smooth Muscles ◽  
Rabbit Aorta ◽  
Vascular Smooth Muscles ◽  
Aortic Smooth Muscle ◽  
Renal Vessels ◽  
Experimental Approaches ◽  
Cellular Ca ◽  
Muscle Specificity

Techniques to dissociate different sites or stores important for Ca2+ entry or release in smooth muscle include washouts of 45Ca in cold La3+-substituted solutions, Scatchard-coordinate plots of Ca2+ uptake, substitution of Sr2+ for Ca2+, and both desaturation and rate coefficient plots. Rabbit aortic smooth muscle is particularly useful because Ca2+ mobilization components can be clearly separated. Other vascular preparations investigated (e.g., renal vessels, coronary arteries) appear to have similar components, but their relative importance varies. Respiratory smooth muscle also has similar Ca2+ mobilization components, but they are less readily dissociated by techniques employed in vascular smooth muscles. In guinea pig trachea, cold La3+ washouts do not retain cellular Ca2+ as well as in other preparations; use of other experimental approaches including the Ca2+ channel entry stimulator, CGP 28392, can demonstrate different Ca2+ uptake mechanisms for K+-stimulated and agonist-induced Ca2+ uptake. In rabbit aorta, CGP 28392 potentiates tension increases elicited with lower concentrations of added K+ but has no effect on norepinephrine-induced contraction. A general model illustrating different Ca2+ entry mechanisms present in three types of smooth muscle provides examples drawn from a spectrum of possible variations in smooth muscle specificity for Ca2+ mobilization.

Effects of Sodium Vanadate on Various Types of Vascular Smooth Muscles

1986 ◽  
Vol 23 (3) ◽  
pp. 113-124 ◽  
Author(s):  
Tomoko Shimada ◽  
Keiichi Shimamura ◽  
Satoru Sunano
Keyword(s):  
Smooth Muscles ◽  
Vascular Smooth Muscles ◽  
Sodium Vanadate

scholarly journals Modeling of the Bayliss‐Effect in Vascular Smooth Muscles

PAMM ◽  
2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Klemens Uhlmann ◽  
Daniel Balzani
Keyword(s):  
Smooth Muscles ◽  
Vascular Smooth Muscles ◽  
Bayliss Effect
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