Modulation of myogenic responsiveness by CO2 in rat diaphragmatic arterioles: role of the endothelium.

The effect of hypercapnia on the myogenic response was determined in arterioles (80- to 100-microm internal diameter) isolated from the diaphragms of rats killed by decapitation. All arterioles were exposed to step changes in intraluminal pressure over a range of 10-200 mmHg and had no flow through their lumen. In five separate groups of vessels (n = 7 per group), PCO2 of the superfusing buffer was adjusted to 40, 60, 80, 90, or 100 mmHg. In three further groups of vessels (n = 7 per group), the endothelium was removed by low-pressure air perfusion (2 ml at 20 mmHg) and PCO2 of the superfusing buffer was adjusted to 40, 80, or 100 mmHg. In endothelium-intact vessels, increasing PCO2 to 80 mmHg enhanced the myogenic response, as reflected by a negative slope of the pressure-diameter relationship (slope = -0.164 +/- 0.03 vs. 0.004 +/- 0.02 for vessels at PCO2 = 40 mmHg, P < 0.05). With a PCO2 of 100 mmHg, dilation accompanied increasing intraluminal pressure and the slope of the pressure-diameter curve was positive (0.154 +/- 0.03, P < 0.05 for difference from vessels at PCO2 = 40 mmHg). In deendothelialized vessels, the curve was shifted upward in a parallel manner during exposure to increased PCO2 levels. Moderate hypercapnia (PCO2 < 80 mmHg) elicits endothelium-dependent enhancement of myogenic tone. Severe hypercapnia (PCO2 > 80 mmHg) inhibits myogenic tone through a direct effect on vascular smooth muscle and through endothelium-dependent inhibitory mechanisms.