A physiogenomic approach to study the regulation of blood pressure.
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. Microarray transcriptome analysis was performed from kidneys 6 h after the induction of acute hypotension. The results were confirmed by real-time PCR. Six functionally known genes (Igfbp1, Xdh, Sult1a1, Mawbp, Por, and Gstm1) and two expressed sequence tages (BI277460 and AI411345) were significantly upregulated. Four of these genes (Igfbp1, Xdh, Por, and Gstm1) have well-characterized functions in the cardiovascular system. The proteins corresponding to Xdh, Por, and Gstm1 are involved in the metabolism of reactive oxygen species (ROS). Because ROS can mediate endothelial dysfunction, we measured the aortic dilatory capacity in thoracic aortic rings. Indeed, vasodilator potency to acetylcholine was largely diminished in hypotensive animals, whereas sodium nitroprusside induced equivalent vasodilations in normotensive and hypotensive animals. The vasodilator potency of the endothelium was partially restored by the superoxide scavenger tiron. Hence, acute hypotension induces a diminished vasodilator potency of the endothelium due to an accelerated degradation of nitric oxide by ROS. The present physiogenomic approach is capable of detecting vasoregulatory mechanisms and may provide deeper insight into the genetics and physiology of blood pressure regulation.
Westhoff
Timm H
TH
Medizinische Klinik IV, Nephrology, Charité, Campus Benamin Franklin, Berlin, Germany.
Scheid
Stefanie
S
Tölle
Markus
M
Kaynak
Bogac
B
Schmidt
Sven
S
Zidek
Walter
W
Sperling
Silke
S
van der Giet
Markus
M
D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001158:Arteries / Q000473:pathology; D001794:Blood Pressure; D016207:Cytokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D020224:Expressed Sequence Tags; D005786:Gene Expression Regulation; D023281:Genomics / Q000379:methods*; D006973:Hypertension; D007022:Hypotension; D007668:Kidney / Q000378:metabolism; D008297:Male; D015233:Models, Statistical; D009599:Nitroprusside / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species; D012084:Renin-Angiotensin System; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
D016207:Cytokines; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013481:Superoxides; D009599:Nitroprusside; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D000109:Acetylcholine