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Anomalous effect of the Beta-3 adrenoceptor antagonist SR 59230A in the rat isolated, pressurized cremaster muscle arteriole
Abstract   Peer reviewed

Anomalous effect of the Beta-3 adrenoceptor antagonist SR 59230A in the rat isolated, pressurized cremaster muscle arteriole

T V Murphy, Shaun L Sandow and L Thiyagarajan
Journal of Vascular Research, Vol.49(Supplement 1), p.26
Australian and New Zealand Microcirculation Society Meeting, 15th (Margaret River, Australia, 30-Nov-2011–03-Dec-2011)
2012
DOI: https://doi.org/10.1159/000334223
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https://doi.org/10.1159/000334223View
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Abstract

Medical and Health Sciences beta-adrenoceptor vasodilatation rat cremaster muscle artery
Beta-1 and beta-2 adrenoceptors are present in small arteries and their activation causes vascular smooth muscle relaxation and vasodilatation. Recent studies suggest beta-3 adrenoceptors may also be present in arteries, and also cause vasodilatation although the idea is controversial (1). This study investigated the effects of beta-3 adrenoceptor ligands on rat isolated, pressurized cremaster muscle arteries with myogenic tone. Male Sprague-Dawley rats were anesthetized (sodium thiopentone 100 mg/kg, i.p.), the cremaster muscles removed and segments of the main (first-order) artery dissected free. Artery segments were cannulated and superfused in a pressure myograph, maintained at an intraluminal pressure of 50 or 120 mmHg. The non-selective beta-adrenoceptor agonist isoprenaline caused a concentration-dependent dilation of the rat cremaster muscle artery, with no effect of pressure on responses (pEC50 50 mmHg, 7.45±0.17; 120 mmHg, 7.38±0.10, n=8, P less 0.05, t-test). The beta-3 adrenoceptorselective agonists CL 316,243 and BRL 37344 had no effect on the diameter of arterioles, at either pressure. Responses to isoprenaline were inhibited by the selective beta-2 adrenoceptor antagonist ICI 118,551 (0.3 μM) but not the selective beta-3 antagonist L 748,337 (0.1 μM). The selective beta-3 antagonist SR 59230A (0.3 μM) caused a rightward-shift of the isoprenaline concentration-response curve in arterioles maintained at 50 mmHg (pEC50 6.59±0.26, n=4, P less 0.05, t-test). In arteries maintained at 120 mmHg, 0.03 and 0.3 μM SR 59230A also reduced the maximum response to isoprenaline (0.03 μM, 67.9±6.9 %; 0.3 μM, 60.4±4.5 %, n=4-8, P less 0.05, t-test). Iberiotoxin (0.1 μM), a blocker of the large-conductance Ca2+-activated K+ channel (BKCa) produced effects similar to SR 59230A on isoprenaline-induced dilation. These observations suggest beta-3 adrenoceptors are not present in the rat cremaster muscle artery and the inhibitory effects of the beta-3 antagonist SR 59230A on isoprenaline-induced dilation of this vessel are caused by an effect unrelated to beta-adrenoceptor antagonism.

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