| Abstrakt: |
Although a-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 µm, n=35) and venules (98±7 µm, n=9) in response to a-adrenergic activation by norepinephrine (10-10 to 10-4 M) in the presence of ß-adrenergic blockade by alprenolol (10-6 M). In contrast to the situation in vivo, a-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 a-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). Furthermore, a-adrenergic activation did not modify microvascular dilatation by adenosine (10-9 to 10-4 M) or nitroglycerin (10-9 to 10-4 M), suggesting that a-adrenergic constriction in vivo is not due to attenuation of cAMP or cGMP-dependent mechanisms of coronary dilatation. In contrast to the lack of constriction in coronary arterioles, canine skeletal muscle arterioles exhibited significant a-adrenergic constriction (-80±4%), maximum diameter change). The coronary venular a-adrenergic constriction was significantly inhibited by both the a1-and a2-adrenergic receptor antagonists, prazosin (10-8 M) and rauwolscine (10-7 M), indicating a mixed population of a1-and a2-adrenergic receptors. These results suggest that coronary arterioles, but not venules, lose a-adrenergic responsiveness during isolation and cannulation, or that the primary coronary microvascular response to a-adrenergic activation is venular constriction. |
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