alpha-adrenergic responses of isolated canine coronary microvessels

Although alpha-adrenergic activation is known to increase coronary microvascular resistance in vivo, the magnitude of its segmental microvascular consequences is not well understood. Quantification of these effects in vivo is hindered by escape mechanisms that minimize the influences of constrictors, and alterations in flow and pressure, which effect microvascular tone by shear stress-dependent and myogenic mechanisms, respectively. To eliminate these confounding influences, we have studied responses in vitro under conditions with these variables controlled. We evaluated the diameter changes of isolated canine coronary arterioles (110 +/- 12 microns, n = 35) response to alpha-adrenergic activation by norepinephrine (10(-10) to 10(-4) M) in the presence of beta-adrenergic blockade by alprenolol (10(-6) M). In contrast to the situation in vivo, alpha-adrenergic activation did not constrict isolated coronary arterioles, but constricted isolated coronary venules in a dose-dependent manner over a range of 10(-10) to 10(-4) M (-27 +/- 3% maximum diameter change). Coronary arteriolar alpha-adrenergic constriction was not promoted by 1) subthreshold or vasoactive doses of the vasoconstrictors KCl, angiotensin II, U46619, endothelin-1, neuropeptide Y or arginine vasopressin, 2) inhibition of the presynaptic uptake of norepinephrine by imipramine (10(-6) M), 3) inhibition of EDRF synthesis by NG-monomethyl-L-arginine (10(-5) M) or 4) inhibition of prostaglandin synthesis by indomethacin (10(-5) M).(ABSTRACT TRUNCATED AT 250 WORDS)