Adrenergic vasomotion in the coronary microcirculation.
The goal of this study was to determine the alpha-adrenergic receptor subtype(s) responsible for constriction at different microvascular levels in the coronary circulation. To accomplish these goals, the epicardial coronary microcirculation of intact beating hearts was viewed through an intravital microscope using stroboscopic epi-illumination. An initial study was designed to establish sites of alpha-adrenergic constriction to norepinephrine in preparations with intact vasomotor tone. For the primary experimental goal, coronary microvascular responses to selective alpha 1-adrenergic (phenylephrine) or alpha 2-adrenergic (BHT-933) agonists were evaluated, when coronary autoregulatory escape mechanisms were blunted during hypoperfusion. Infusion of norepinephrine decreased diameter of arterial vessels greater than 100 microns in diameter, but downstream coronary arterioles dilated significantly, representing autoregulatory escape from adrenergic vasoconstriction. In studies designed to examine the adrenergic receptor subtype (during hypoperfusion), phenylephrine produced modest constriction of vessels throughout the microcirculation (6-9% decrease in diameter), whereas BHT-933 produced marked constriction of small coronary microvessels, those less than 100 microns in diameter (24% decrease in diameter). From these results we conclude: 1) norepinephrine infusion causes disparate responses in the coronary microvasculature: constriction occurs in vessels greater than 100 microns in diameter, but dilation, via autoregulatory escape, predominates in vessels less than 100 microns in diameter; 2) alpha 1-adrenergic receptors are located in coronary arterioles and arteries; and 3) alpha 2-adrenergic receptors are preferentially located in small coronary arterioles. Thus, alpha 1- and alpha 2-adrenergic activation can produce dissimilar constrictor effects in the coronary microcirculation during hypoperfusion.
Chilian
W M
WM
Department of Medical Physiology, Microcirculation Research Institute, Texas A&M University, College Station.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002415:Cats; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; C015603:azepexole