Mechanisms Involved in the Actions of Stimulant Drugs on Vascular Smooth Muscle

Bolton, T. B.

doi:10.1007/978-1-4615-9471-0_3

Cited by 2 publications

(1 citation statement)

References 53 publications

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“…Vasoconstriction to KCl which promotes Ca 2+ influx through voltage operated calcium channels without interacting with a 1 -adrenoceptors (Bean, 1989;Bolton, 1986) was similar in both strains. Thus, the lower vasoconstriction evoked by phenylephrine in SHR rats should be ascribed to a specific alteration of a 1 -adrenoceptor-mediated response rather than to an alteration in the contractile machinery.…”

Section: Discussionmentioning

confidence: 87%

Modelling the changes due to the endothelium and hypertension in the α‐adenoreceptor‐mediated responses of rat aorta

Tabernero

Giraldo

Vila³

1999

Journal of Autonomic Pharmacology

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The present study focuses on the role of endothelium on alpha1-adrenoceptor-mediated vasoconstriction in aorta from Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). To define and quantify changes in the parameters governing agonism at alpha1-adrenoceptor by hypertension and/or endothelium, the operational model of analysis was used. In either endothelium intact or denuded aorta, the sensitivity (P < 0.001) and the maximum contraction (P < 0.05) to phenylephrine were smaller in SHR than in WKY. However, in each strain of rats, removal of endothelium increased the sensitivity (P < 0.001) to phenylephrine but reduced (P < 0.05) KCl-evoked vasoconstriction, suggesting a modulation of these responses by the endothelium. The observed differences in sensitivity and maximum contraction are interpreted in terms of the operational parameters: Em, the maximum possible effect; pK(A), the agonist affinity; alpha, the agonist efficacy and n, the slope for the function relating receptor occupancy to pharmacological effect. The estimated parameters reflected differences, between strains, in the signal transduction processes linked to alpha1-adrenoceptor stimulation ascribed to the presence of the endothelium. N(G)-nitro-L-arginine methyl ester (L-NAME), enhanced to a similar extend in both rat strains the sensitivity (P < 0.001) and the maximum contraction to phenylephrine. Indomethacin reduced the maximum contraction to phenylephrine by 56.85% in SHR and by 11.80% in WKY suggesting that contracting prostanoids play a more major role in this response in SHR than in WKY. Nevertheless, these inhibitors were without effect on denuded vessels from both strains suggesting that NO and cyclooxygenase products from the media or the adventitia do not play a role on the phenylephrine-mediated responses. The studied endothelial factors partially explain the observed differences in modulation of alpha1-adrenoceptor responses by the endothelium but suggest the participation of other compounds released by the endothelium.

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Section: Discussionmentioning

confidence: 87%

Modelling the changes due to the endothelium and hypertension in the α‐adenoreceptor‐mediated responses of rat aorta

Tabernero

Giraldo

Vila³

1999

Journal of Autonomic Pharmacology

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Microvascular effects of atrial natriuretic factor: interaction with alpha 1- and alpha 2-adrenoceptors.

Faber

Gettes

Gianturco

1988

Circulation Research

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The cremaster skeletal muscle of anesthetized rats was denervated and extended with intact circulation into a tissue bath. Intravital microscopy was used to measure microvessel diameter at three different anatomical levels within the microcirculation: large distributing arterioles (x control diameter = 100 +/- 7 micron), large capacitance venules (147 +/- 8 micron), and small terminal arterioles (17 +/- 1 micron). Norepinephrine (NE) was added to the cremaster bath to produce intermediate reductions in diameter of large arterioles and venules (55% and 38% of maximum constriction, respectively). In the presence of NE tone, bath-added atrial natriuretic factor (ANF) produced concentration-dependent dilation of both arterioles and venules. Arteriolar IC25 = 18 pmol and IC50 = 1.2 X 10(-10) M; venules exhibited similar sensitivity. However, the highest ANF concentration examined (10(-7) M) only reversed NE-induced tone by 70%. In a second large vessel group ANF completely reversed constriction induced by the alpha 1-adrenoceptor agonist, phenylephrine, in the presence of 5 X 10(-7) M yohimbine. However, vessels constricted with the alpha 2-receptor agonist UK-14,304 (in the presence of 10(-8) M prazosin) were insensitive to ANF. A third group of terminal arterioles, which possess considerable spontaneous "intrinsic" tone, were studied in the absence of alpha-receptor agonists. Significant dilation occurred at greater than 10(-7) M, and the maximal response was only 25% of complete dilation with adenosine. These data indicate that ANF exhibits a high potency and selectivity for reversal of alpha 1-adrenoceptor-mediated constriction of large arterioles and venules. Constriction produced by alpha 2-adrenoceptor occupation or by nonadrenergic "intrinsic" mechanisms appears to be insensitive to ANF. We propose that the ability of ANF to reduce microvascular resistance depends on the relative contribution of alpha 1-, alpha 2-, and intrinsic vasoconstrictor components to the prevailing level of smooth muscle tone. Differences in these components among regional circulations and between arterial and venous smooth muscle may contribute to the systemic hemodynamic pattern produced by ANF.

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Mechanisms Involved in the Actions of Stimulant Drugs on Vascular Smooth Muscle

Cited by 2 publications

References 53 publications

Modelling the changes due to the endothelium and hypertension in the α‐adenoreceptor‐mediated responses of rat aorta

Modelling the changes due to the endothelium and hypertension in the α‐adenoreceptor‐mediated responses of rat aorta

Microvascular effects of atrial natriuretic factor: interaction with alpha 1- and alpha 2-adrenoceptors.

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