AJP - Heart and Circulatory Physiology, Vol 256, Issue 2 334-H340, Copyright © 1989 by American Physiological Society
Alpha 1-adrenergic control of contractility and coronary flow in the perfused rat heart
S. J. Edwards, S. Rattigan, E. Q. Colquhoun, S. C. Lockwood, E. A. Woodcock and M. G. Clark
Department of Biochemistry, University of Tasmania, Hobart, Australia.
Prazosin inhibition of phenylephrine plus propranolol (alpha 1-adrenergic
agonist combination)-mediated inotropy, oxygen uptake, and coronary
vasoconstriction of the perfused rat heart were compared with prazosin
binding under identical conditions. Binding studies for the perfused heart
indicated a population of high-affinity sites (Kd, 0.41 nM; Bmax, 13.2
pmol/g wet wt). Phenylephrine (50 microM) plus dl-propranolol (10 microM)
did not significantly alter binding of 3.9 nM prazosin. The alpha 1-agonist
combination mediated a dose-dependent increase in tension development and
oxygen uptake and a decrease in coronary flow, each of which was inhibited
by prazosin. The concentration of prazosin required for half-maximal
inhibition of inotropy and oxygen uptake produced by 50-100 microM
phenylephrine was 30-40 nM; no inhibition occurred at 2-3 nM prazosin
concentration when binding sites were saturated. One nanomolar prazosin was
required for half-maximal inhibition of the flow decrease produced by 10
microM phenylephrine. It is concluded that less than 1% of the alpha
1-binding sites are required for full development of inotropy and that this
may result from an excess of binding sites or a small population of
low-affinity receptors.
