regulatory effects of hypoxia-inducible factor 1alpha on vascular reactivity and its mechanisms following hemorrhagic shock in rats.

摘要

The purpose of the present study is to investigate the regulatory effect of hypoxia-inducible factor 1alpha (HIF-1alpha) on vascular reactivity and its mechanism after hemorrhagic shock (HS). Gene expression of HIF-1alpha and its downstream molecules, including eNOS, iNOS, cyclooxygenase 2 (COX-2), and heme oxygenase 1 (HO-1), and plasma nitric monoxide (NO), prostaglandin (PGI), and whole blood carbon monoxide (CO) were determined after HS in rats with or without oligomycin, the specific antagonist of HIF-1alpha. The vascular reactivity was determined via observing the constriction initiated by norepinephrine in isolated organ perfusion system. The results indicated that HIF-1alpha, eNOS, iNOS, HO-1, and COX-2 messenger RNA expression exhibited a time-dependent increase after HS, although the expression of these genes and their products, NO, CO, and PGI were suppressed by oligomycin to some extent. The vascular reactivity revealed a biphasic change, which was increased compensatorily at the early stage of HS (immediate to 1 h after shock) and decreased progressively at the decompensatory period after 4 h of shock. Oligomycin treatment partly inhibited the vascular reactivity at early stage (immediate to 1 h after shock) and improved it at decompensatory period at 4 to 6 h after shock (P < 0.01). The results suggested that HIF-1alpha plays an important regulatory role in the change of vascular reactivity after HS in rats. The possible mechanism of HIF-1alpha regulating vascular reactivity is closely related to its regulation on the expression of eNOS, iNOS, HO-1, COX-2 and the production of NO, CO and PGI.