The order of dilator-constrictor administration affects stenotic hemodynamic responses

This study tested the hypothesis that, due to intraluminal pressure changes, the order of constrictor-dilator administration alters stenotic hemodynamic responses. Canine carotid arteries were perfused with a physiologic salt solution under constant pressure (100 mm Hg). An intraluminal stenosis partially obstructed the arteries. Pressures proximal and distal to the artery and the flow were continually recorded as norepinephrine (10(-9)-10(-6) M) was added to the perfusate. Adding diltiazem (10(-7) M) before norepinephrine shifted the effective half maximum dose (ED50) of the norepinephrine flow curve from 7.35 +/- 0.66 X 10(-8) M to 6.39 +/- 0.72 X 10(-7) M (p < 0.05). More important, adding 10(-7) M diltiazem after norepinephrine-induced constriction did not reestablish stenotic pressure or flow: A 30-fold increase in diltiazem concentration (3.16 X 10(-6)M) was required to reestablish stenotic pressure (62.6 +/- 4.4 mm Hg) and flow (25.4 +/- 3.2 ml/min). Similarly, adding nitroglycerin (10(-7) M) before norepinephrine shifted the ED50 from 7.21 +/- 0.58 X 10(-8) to 5.94 +/- 0.78 X 10(-6) (p < 0.05). Adding 10(-7) M nitroglycerin after norepinephrine did not reestablish stenotic pressure or flow: 3.16 X 10(-6) M nitroglycerin was required to reestablish stenotic pressure (59.2 +/- 4.8 mm Hg) and flow (23.2 +/- 2.7 mL/min). This constrictor-dilation history did not occur in isolated arterial rings (norepinephrine + nitroglycerin = 38.1 +/- 13.9 g/cm2; nitroglycerin + norepinephrine = 42.2 +/- 9.4 g/cm2; p = not significant [NS]) or in normal arteries (norepinephrine + nitroglycerin = 4.89 +/- 0.14 mm [external diameter]; nitroglycerin + norepinephrine = 4.92 +/- 0.23 mm; p = NS). In stenotic arteries, intraluminal pressure influenced the order of constrictor-dilator administration on hemodynamic response, which was not observed in isolated arterial rings or in normal arteries. This pressure-dependent sensitivity affects vasomotor tone and may be important in the pathophysiology of ischemia.