gms | German Medical Science

Several vasoregulatory systems including the renin-angiotensin system, sympathetic vasoregulation, and cytokine release have been studied extensively. The aim of the present study was to establish a physiogenomic screening model for differentially expressed genes in the regulation of blood pressure that might give a hint as to new vasoregulatory mechanisms. We induced acute hypotension in normotensive rats, assuming that vasoregulatory systems will counteract hypotension. 3 ml blood were withdrawn in five animals by ventricular punction, whereas five control rats underwent ventricular punction without bleeding. Blood withdrawal induced a significant decrease of systolic bood pressure (31±5%, n=5). 6 hours after ventricular puncture kidneys were extracted. After isolation and purification of RNA double-stranded cDNA was synthesized and retranslated to biotin-labeled cRNA, which was hybridized to an Affymetrix rat genome 230A array containing 15923 probe sets (Affymetrix). The results of the most significantly differentially expressed genes were confirmed by real-time PCR. Six functionally known genes (Igfbp1, Xdh, Sult1a1, Mawbp, Por, Gstm1) and two ESTs (BI277460 and AI411345) were significantly upregulated. Four of these genes (Igfbp1, Xdh, Por, Gstm1) have well characterized functions in the cardiovascular system. The proteins corresponding to Xdh (xanthine dehydrogenase), Por (cytochrome P450 oxidoreductase) and Gstm1 (Glutathione S-transferase, mu 1) are involved in the metabolism of reactive oxygen species (ROS). Furthermore, the EST AI411345 is highly similar (99%) to mouse proline oxidase. Proline oxidase is a mitochondrial enzyme catalyzing the conversion of proline to pyrroline-5-carboxylate with the concomitant transfer of electrons to cytochrome c and is capable of generating reactive oxygen species.

Increasing experimental and clinical data describe a possible role of elevated oxidative stress in arterial hypertension. The present work documents that ROS might contribute to the physiological regulation of blood pressure as well.