Functional responses in the a1AB- adrenoceptor knockout mouse indicate that the a1D- adrenoceptor has a role in the contraction of small mesenteric arteries

Methven, L., Hamill, C., MacMillan, J., Daly, C.J. , McGrath, J.C. and Simpson, P.C. (2008) Functional responses in the a1AB- adrenoceptor knockout mouse indicate that the a1D- adrenoceptor has a role in the contraction of small mesenteric arteries. Journal of Vascular Research, 45(Supple), 45--. (doi: 10.1159/000113929)

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The alpha1A-adrenoceptor (AR) mediates vasoconstriction in mouse small mesenteric arteries, but the alpha1B-AR and/or alpha1D-AR may also contribute to the contractile response in these arteries. In the alpha1AB-knockout (KO), where only the alpha1D-AR remains, functional studies have been performed only in the heart. The present study examined the agonist-induced contractile responses in small mesenteric arteries of the alpha1AB-KO and wild type (WT) mouse. Methods: Double knockout alpha1AB -/- mice were generated as previously described. First order mesenteric arteries were dissected from male, four-month old alpha1ABKO and WT control C57Bl/6J mice. 2 mm rings of artery were mounted in 4-chamber wire myographs. Cumulative concentration response curves were constructed in half log increments (1 nM-100 microM) to: the nonselective alpha1-AR agonist, phenylephrine; the alpha1A-AR selective agonist, A-61603; and the non-adrenergic agonist, 5-hydroxytryptamine. Results: Phenylephrine produced concentration-dependent contractions in both mouse strains (Table). In the alpha1AB-KO, the maximum response was significantly reduced but sensitivity was significantly higher, compared to the WT mouse. A-61603 produced concentration dependent contractions in the WT mouse but both maximum response and sensitivity to A-61603 were significantly lower in the alpha1AB-KO. 5-hydroxytryptamine had similar potency in the alpha1AB-KO and WT mouse. Conclusion: This study has examined functional responses in the vasculature of the alpha1AB-KO for the first time. The non-adrenergic response was comparable in the WT mouse and alpha1AB-KO, suggesting that any difference observed in the alpha1-AR-mediated responses was not due to a reduction in the overall contractility of the arteries. Based on the high efficacy of A-61603 in the WT mouse, this study confirms that alpha1-ARmediated contractions in small mesenteric arteries are predominantly mediated by the alpha1A-subtype of AR. The adrenergic responses in the alpha1AB-KO indicate that the alpha1D-AR mediates a contractile response in small mesenteric arteries and, therefore, suggest that the alpha1D-AR contributes to the vasoconstriction of resistance arteries in the WT mouse, consistent with a potential role for the alpha1D-AR in blood pressure regulation.

Item Type:Articles
Glasgow Author(s) Enlighten ID:McGrath, Professor John and Methven, Dr Laura and Daly, Professor Craig and Macmillan, Mrs Joyce
Authors: Methven, L., Hamill, C., MacMillan, J., Daly, C.J., McGrath, J.C., and Simpson, P.C.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Journal of Vascular Research
Journal Abbr.:J. Vasc. Res.
Publisher:S. Karger AG
ISSN (Online):1423-0135
Published Online:26 August 2009

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