Contractile responses of isolated vascular smooth muscle during prolonged exposure to anoxia

Detar, R; Df, Bohr

doi:10.1152/ajplegacy.1972.222.5.1269

Cited by 38 publications

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“…It is interesting that the findings from the present study contrast markedly with those of Detar & Bohr (1968, 1972, who obtained a paradoxical relaxation to oxygen in adrenaline-stimulated rabbit aorta exposed to prolonged hypoxia. The reasons for these discrepancies remain obscure.…”

Section: Mechanisms Responsiblefor Po2-dependent Changes In Contracticontrasting

confidence: 99%

“…The reasons for these discrepancies remain obscure. However, differences in study design, namely species, form of preparation and agonist employed might be critical in producing the hypoxic 'adaptation' in vascular contractility described by Detar & Bohr (1972).…”

Section: Mechanisms Responsiblefor Po2-dependent Changes In Contractimentioning

confidence: 99%

“…A majority of contractions to both adrenoceptor agonists and KCl, studies have investigated major systemic arteries, while a return to control Po2 restored contractile responses (Griesmer & Coret, 1960;Coret & Hughes, 1964;Detar & Bohr, 1968;Ebeigbe et al, 1980a;Marriott, 1987). In contrast, Detar & Bohr (1972) found that when rabbit aorta had been exposed to hypoxia for 80h, the magnitude of contraction produced by adrenaline was then as great as that produced under the original control conditions and that re-oxygenation produced relaxation rather than further contraction; this change in behaviour during prolonged exposure to hypoxia was termed 'adaptation'. When rabbit aorta was exposed to acute episodes of hypoxia followed by re-oxygenation, Ebeigbe and co-workers (1980b) demonstrated a correlation between hypoxic depression of contractions to noradrenaline or KCI and a reduction in 45Ca uptake.…”

Section: Introductionmentioning

confidence: 99%

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The effects of verapamil upon noradrenaline‐induced contraction of the rat isolated aorta following acute and prolonged alterations in PO₂

Marriott

1989

British J Pharmacology

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1 Noradrenaline (NA; ED9Q) caused a contraction of the rat aorta which could be separated into two components, a rapid response mediated by release of intracellular Ca2+ and a more slowly developing contraction which relied principally upon Ca2 + influx. 2 Exposure to acute (30min) hypoxia has been previously shown to reduce the NA-induced contraction (by 28.0 + 2.7%, n = 168) which recovered completely upon re-oxygenation (recovery response). In the present study, prolonged exposure to hypoxia (70h) caused a more pronounced reduction (39.7 + 3.0%, n = 90) of the NA-induced contraction, but, re-oxygenation then produced incomplete recovery to 77.9 + 3.9% (n = 90) of the control response.3 Prolonged exposure to 95% 02 caused a 36.5 + 3.1% (n = 42) reduction of NA-induced contractions, whereas prolonged exposure to 21% 02 only caused a small (12.6 + 3.4%, n = 6) depression of these responses. 4 The component of the NA-induced contraction mediated by release of intracellular Ca2+ is 39.8 + 1.3% (n = 83) of the NA contraction in Ca-containing Krebs solution and was previously found to be unaffected by acute hypoxia. However, following prolonged exposure to either hypoxia or 21% 02, this component only reached 30.7 + 2.2% (n = 32) or 28.3 + 0.9% (n = 6) of the control response, respectively. Prolonged exposure to 95%°2 caused a more pronounced reduction of this component of contraction which then reached 19.1 + 2.1% (n = 12) of the control response. 5 Verapamil (10nM-10uM) produced similar concentration-dependent reductions of NA-induced contractions elicited during control conditions or acute hypoxia; under these conditions, 1 gIM verapamil caused a 34.1 + 6.9% (n = 6) and a 41.8 + 2.9% (n = 18) reduction of these responses respectively. However, recovery responses caused by re-oxygenation of tissues exposed to acute hypoxia were more sensitive to verapamil which, at a concentration of 1 pm, caused a 59.2 + 2.7% (n = 18) reduction of these responses. Verapamil (10 nM-10 MM) also caused similar pronounced concentration-dependent reductions of contractions elicited during prolonged exposure to normoxia or hyperoxia and of recovery responses obtained following re-oxygenation of tissues exposed to prolonged hypoxia; 1 JM verapamil caused a 62.5 + 1.1% (n = 6), 77.2 + 3.8% (n = 12) and a 68.0 + 4.3% (n = 12) reduction of these responses respectively. In contrast, contractions elicited during prolonged hypoxia were less sensitive to verapamil which at a concentration of 1 JM only caused a 16.2 + 2.2% (n 12) reduction of these responses. 6 The present study indicates that prolonged exposure of the rat aorta to either hypoxic or oxygenated conditions causes attenuation of NA-induced contraction. However, these effects are also accompanied by changes in tissue Ca2+ handling which differ under each condition and might account for the observed modifications in tissue sensitivity to the calcium-entry blocker verapamil.

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Section: Mechanisms Responsiblefor Po2-dependent Changes In Contracticontrasting

confidence: 99%

Section: Mechanisms Responsiblefor Po2-dependent Changes In Contractimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The effects of verapamil upon noradrenaline‐induced contraction of the rat isolated aorta following acute and prolonged alterations in PO₂

Marriott

1989

British J Pharmacology

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“…Hypoxia augments contractile responses to several vasoactive agents (potassium chloride, 5-hydroxytryptamine, and prostaglandin F2G) in canine isolated blood vessels, including the coronary artery (Detar & Bohr, 1972; Vanhoutte, 1976;Van Nueten et al, 1980;De Mey & Vanhoutte, 1982;Rubanyi & Vanhoutte, 1985;Katusic & Vanhoutte, 1986). Removal of the endothelium greatly reduces or abolishes the hypoxic facilitation of the contraction (De Mey & Vanhoutte, 1982;Rubanyi & Vanhoutte, 1985;Katusic & Vanhoutte, 1986).…”

Section: Introductionmentioning

confidence: 99%

Flunarizine inhibits endothelium‐dependent hypoxic facilitation in canine coronary arteries through an action on vascular smooth muscle

Iqbal¹,

Vanhoutte²

1988

British J Pharmacology

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1 Hypoxia augments contractile responses to several vasoactive agents in canine isolated coronary arteries with intact endothelium. Calcium antagonists inhibit the further increases in tension caused by hypoxia. The present experiments were designed to determine whether the calcium-antagonist flunarizine would inhibit hypoxic contractions in isolated blood vessels through an action on the endothelium or on the vascular smooth muscle. 2 Rings of canine coronary arteries, with or without endothelium, were suspended at optimal length for isometric tension recording in organ chambers filled with modified Krebs-Ringer bicarbonate solution.3 Hypoxia (95% N2 and 5% C02) augmented contractile responses to prostaglandin F2.(2 x 106 M); removal of the endothelium abolished this hypoxic facilitation. 4 Flunarizine (5 x 10-5-5 x 10-7M) exerted a long-lasting inhibition of the hypoxic facilitation in a concentration-dependent manner. Flunarizine did not inhibit the response to prostaglandin F2,. 5 To differentiate between the response of smooth muscle and the endothelium, strips of coronary arteries without endothelium were layered with strips with or without endothelium. Hypoxia augmented contractions only in layered preparations with endothelium. Flunarizine prevented the hypoxic contractions in layered preparations in which only the smooth muscle was treated with flunarizine. In contrast, when only the endothelium was treated, no or minimal inhibition of the hypoxic contraction occurred with flunarizine (10' and 5 x 10-5M, respectively).6 These experiments indicate that the calcium antagonist flunarizine inhibits endotheliumdependent hypoxic facilitation in canine coronary arteries primarily through its action on vascular smooth muscle.

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“…The physiological consequences of organ culture are often quite distinct from those of cell culture. Different components of the mechanism of hypoxia-induced vasodilation have been identified using organ culture or storage as a model (4,7). For instance, there is an endotheliumdependent relaxation after reoxygenation from hypoxia (4) that depends greatly on the duration of storage of the vessel at 4°C (25).…”

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confidence: 99%

Hypoxic vasorelaxation inhibition by organ culture correlates with loss of Kv channels but not Ca²⁺ channels

Thorne

Conforti

Rutgeerts

2002

American Journal of Physiology-Heart and Circulatory Physiology

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vasorelaxation inhibition by organ culture correlates with loss of Kv channels but not Ca 2ϩ channels. Am J Physiol Heart Circ Physiol 283: H247-H253, 2002; 10.1152/ajpheart.00569.2001.-We (Thorne GD, Shimizu S, and Paul RJ. Am J Physiol Cell Physiol 281: C24-C32, 2001 have recently shown that organ culture for 24 h specifically inhibits relaxation to acute hypoxia (95% N2-5% CO2) in the porcine coronary artery. Here we show similar results in the porcine carotid artery and the rat and mouse aorta. In the coronary artery, part of the inability to relax to hypoxia after organ culture is associated with a concomitant loss in ability to reduce intracellular Ca 2ϩ concentration ([Ca 2ϩ ]i) during hypoxia (Thorne GD, Shimizu S, and Paul RJ. Am J Physiol Cell Physiol 281: C24-C32, 2001). To elucidate the mechanisms responsible for the loss of relaxation to hypoxia, we investigated changes in K ϩ and Ca 2ϩ channel activity and gene expression that play key roles in [Ca 2ϩ ]i regulation in vascular smooth muscle (VSM). Reduced mRNA expression of O2-sensitive K ϩ channels (Kv1.5 and Kv2.1) was shown by reverse transcriptase-polymerase chain reaction in the rat aorta. In contrast, no change in other expressed voltagegated K ϩ channels (Kv1.2 and Kv1.3) or Ca 2ϩ channel subtypes was found. Modified K ϩ channel expression is supported by functional evidence indicating a reduced response to general K ϩ channel activation, by pinacidil, and to specific voltage-dependent K ϩ (Kv) channel blockade by 4-aminopyridine. In conclusion, organ culture decreases expression of specific Kv channels. These changes are consistent with altered mechanisms of VSM contractility that may be involved in Ca 2ϩ -dependent pathways of hypoxia-induced vasodilation.hypoxia; coronary; potassium channel; smooth muscle THE MECHANISM of hypoxia-induced vasodilation is not completely defined. However, it has in part been attributed to the possible involvement of various types of ion channels. K ϩ channel activation and inactivation has been suggested to contribute to hypoxic vasodilation and vasoconstriction, respectively, in different tissue varieties (13,18,28,32 Organ culture evokes a variety of cellular changes that alter normal physiological function. The physiological consequences of organ culture are often quite distinct from those of cell culture. Different components of the mechanism of hypoxia-induced vasodilation have been identified using organ culture or storage as a model (4, 7). For instance, there is an endotheliumdependent relaxation after reoxygenation from hypoxia (4) that depends greatly on the duration of storage of the vessel at 4°C (25). We have shown that organ culture at 37°C for 24 h markedly reduces relaxation to hypoxia (29). It has also been shown that altered Ca 2ϩ handling in organ cultured vascular smooth muscle (VSM) influences force development (14,15). Recently, increases in L-type Ca 2ϩ channel mRNA and the dihydropyridine receptor have been demonstrated in cardiac myocytes after culture (6). In addition, N-type ...

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Contractile responses of isolated vascular smooth muscle during prolonged exposure to anoxia

Cited by 38 publications

References 0 publications

The effects of verapamil upon noradrenaline‐induced contraction of the rat isolated aorta following acute and prolonged alterations in PO₂

The effects of verapamil upon noradrenaline‐induced contraction of the rat isolated aorta following acute and prolonged alterations in PO₂

Flunarizine inhibits endothelium‐dependent hypoxic facilitation in canine coronary arteries through an action on vascular smooth muscle

Hypoxic vasorelaxation inhibition by organ culture correlates with loss of Kv channels but not Ca²⁺ channels

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Contractile responses of isolated vascular smooth muscle during prolonged exposure to anoxia

Cited by 38 publications

References 0 publications

The effects of verapamil upon noradrenaline‐induced contraction of the rat isolated aorta following acute and prolonged alterations in PO2

The effects of verapamil upon noradrenaline‐induced contraction of the rat isolated aorta following acute and prolonged alterations in PO2

Flunarizine inhibits endothelium‐dependent hypoxic facilitation in canine coronary arteries through an action on vascular smooth muscle

Hypoxic vasorelaxation inhibition by organ culture correlates with loss of Kv channels but not Ca2+ channels

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The effects of verapamil upon noradrenaline‐induced contraction of the rat isolated aorta following acute and prolonged alterations in PO₂

The effects of verapamil upon noradrenaline‐induced contraction of the rat isolated aorta following acute and prolonged alterations in PO₂

Hypoxic vasorelaxation inhibition by organ culture correlates with loss of Kv channels but not Ca²⁺ channels