Am. J. Respir. Crit. Care Med., Volume 156, Number 5, November 1997, 1572-1578

Hyporeactivity of Rat Diaphragmatic Arterioles after Exposure to Hypoxia In Vivo
Role of the Endothelium

MOURAD TOPORSIAN and MICHAEL E. WARD

Division of Critical Care Medicine, Royal Victoria Hospital and the Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada

The effect of prior in vivo hypoxia on the in vitro responses to changes in transmural pressure, -adrenoceptor activation, and depolarization with KCl were evaluated in first-order diaphragmatic arterioles. Rats (n = 14 per group) were exposed to normoxia (controls) or to hypoxia (inspired O₂ concentration = 10%) for 12 or 48 h. The arteriolar pressure-diameter relationships were recorded over a pressure range from 10 to 200 mm Hg. In separate groups of arterioles (n = 12 per group), the diaphragmatic arteriolar responses to phenylephrine (10⁸ to 10⁵ M) or KCl (10 to 100 mM) were determined after exposure to either room air or hypoxia for 48 h. In half of the arterioles studied, the endothelium was removed. After 12 h of hypoxia, the pressure-diameter relationship was normal in endothelialized arterioles but was shifted upward in de-endothelialized vessels (p < 0.05). After 48 h of hypoxia, the constrictor response to increasing transmural pressure was severely suppressed in all arterioles. The intraluminal diameters during activation with phenylephrine and KCl were larger in arterioles from rats exposed to hypoxia (103 ± 8 and 81 ± 7 µm, respectively) than in control arterioles (41 ± 5 and 54 ± 6 µm, respectively; p < 0.05 for differences). During maximum phenylephrine- and KCl-induced constriction in de-endothelialized arterioles, diameters averaged 125 ± 8 and 105 ± 8 µm, respectively, for arterioles from hypoxic rats and 32 ± 6 and 40 ± 5 µm, respectively, for arterioles from control vessels. Exposure to hypoxia results in impairment of diaphragmatic arteriolar smooth muscle reactivity and reversal of the normal inhibitory influence of the endothelium on diaphragmatic arteriolar tone.

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