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Am J Physiol Heart Circ Physiol 284: H1104-H1109, 2003. First published December 5, 2002; doi:10.1152/ajpheart.00441.2002
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Vol. 284, Issue 4, H1104-H1109, April 2003

alpha 1-Adrenergic receptor responses in alpha 1AB-AR knockout mouse hearts suggest the presence of alpha 1D-AR

Lynne Turnbull, Diana T. McCloskey, Timothy D. O'Connell, Paul C. Simpson, and Anthony J. Baker

Departments of Medicine, Radiology and Cardiovascular Research Institute, University of California, San Francisco 94143; and the Veterans Affairs Medical Center, San Francisco, California 94121

Two functional alpha 1-adrenergic receptor (AR) subtypes (alpha 1A and alpha 1B) have been identified in the mouse heart. However, it is unclear whether the third known subtype, alpha 1D-AR, is also present. To investigate this, we determined whether there were alpha 1-AR responses in hearts from a novel mouse model lacking alpha 1A- and alpha 1B-ARs (double knockout) (ABKO). In Langendorff-perfused hearts, alpha 1-ARs were stimulated with phenylephrine. For ABKO hearts, phenylephrine reduced left ventricular pressure and coronary flow (to 87 ± 2% and 86 ± 4% of initial, respectively, n = 11, P < 0.01). These effects were blocked by prazosin and 8-{2-[4-(2-methoxyphenyl)-1-piperazinyl]-8-azaspirol[4,5]decane-7,9-dione} dihydrochloride, suggesting that alpha 1D-AR-mediated responses were present. In contrast, right ventricular trabeculae from ABKO hearts did not respond to phenylephrine, suggesting that in ABKO perfused hearts, the effects of phenylephrine were not mediated by direct actions on cardiomyocytes. A novel finding was that alpha 1-AR stimulation caused positive inotropy in the wild-type mouse heart, in contrast to negative inotropy observed in mouse cardiac muscle strips. We conclude that mouse hearts lacking alpha 1A- and alpha 1B-ARs retain functional alpha 1-AR responses involving decreases of coronary flow and ventricular pressure that reflect alpha 1D-AR-mediated vasoconstriction. Furthermore, alpha 1-AR inotropic responses depend critically on the experimental conditions.

Langendorff-perfused heart; phenylephrine; myocardial contractility; coronary arteries


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