Renin, angiotensinogen, and kallikrein gene expression in two-kidney Goldblatt hypertensive rats. 1993

S S el-Dahr, and S Dipp, and S Guan, and L G Navar
Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana 70112.

An imbalance in the activity of the vasopressor renin-angiotensin and vasodepressor kallikrein-kinin systems may play an important role in the pathogenesis of hypertension after unilateral renal artery constriction. To test this hypothesis, we examined the expression of the renin, angiotensinogen (Ao), and tissue kallikrein genes 7 and 25 days after placement of a 0.25-mm clip on the left renal artery of rats. One week after clipping, renin mRNA levels were 4.6-fold higher in the clipped and 50% lower in the nonclipped kidneys compared with kidneys from sham-operated rats. At 25 days, renin mRNA levels in the clipped kidneys were not different from sham kidneys, but were suppressed to almost undetectable levels in the nonclipped kidneys. Steady-state Ao mRNA levels in the clipped kidneys were not different from those of nonclipped or sham kidneys at either 7 or 25 days. However, at 25 days, Ao mRNA levels were lower in the liver (70%), left ventricle (55%), and aorta (45%) of clipped than sham-operated rats. The expression of the renal kallikrein gene was unchanged at 7 days and was suppressed by 50% at 25 days. These results are consistent with the notion that activation of the intrarenal renin-angiotensin system occurs during the initial phase of the two-kidney, one-clip hypertension model. The renal kallikrein gene, in marked contrast to renin, becomes downregulated in the chronic phase. The differential regulation of renin-angiotensin and kallikrein genes may be an important pathogenetic factor in renovascular hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D006978 Hypertension, Renovascular Hypertension due to RENAL ARTERY OBSTRUCTION or compression. Hypertension, Goldblatt,Goldblatt Syndrome,Goldblatt Hypertension,Renovascular Hypertension,Syndrome, Goldblatt
D007610 Kallikreins Proteolytic enzymes from the serine endopeptidase family found in normal blood and urine. Specifically, Kallikreins are potent vasodilators and hypotensives and increase vascular permeability and affect smooth muscle. They act as infertility agents in men. Three forms are recognized, PLASMA KALLIKREIN (EC 3.4.21.34), TISSUE KALLIKREIN (EC 3.4.21.35), and PROSTATE-SPECIFIC ANTIGEN (EC 3.4.21.77). Kallikrein,Kininogenase,Callicrein,Dilminal,Kallidinogenase,Kalliginogenase,Kallikrein A,Kallikrein B',Kallikrein Light Chain,Kinin-Forming Enzyme,Padutin,alpha-Kallikrein,beta-Kallikrein,beta-Kallikrein B,Enzyme, Kinin-Forming,Kinin Forming Enzyme,Light Chain, Kallikrein,alpha Kallikrein,beta Kallikrein,beta Kallikrein B
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008297 Male Males
D012083 Renin A highly specific (Leu-Leu) endopeptidase that generates ANGIOTENSIN I from its precursor ANGIOTENSINOGEN, leading to a cascade of reactions which elevate BLOOD PRESSURE and increase sodium retention by the kidney in the RENIN-ANGIOTENSIN SYSTEM. The enzyme was formerly listed as EC 3.4.99.19. Angiotensin-Forming Enzyme,Angiotensinogenase,Big Renin,Cryorenin,Inactive Renin,Pre-Prorenin,Preprorenin,Prorenin,Angiotensin Forming Enzyme,Pre Prorenin,Renin, Big,Renin, Inactive
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D000808 Angiotensinogen An alpha-globulin of about 453 amino acids, depending on the species. It is produced by the liver in response to lowered blood pressure and secreted into blood circulation. Angiotensinogen is the inactive precursor of the ANGIOTENSINS produced in the body by successive enzyme cleavages. Cleavage of angiotensinogen by RENIN yields the decapeptide ANGIOTENSIN I. Further cleavage of angiotensin I (by ANGIOTENSIN CONVERTING ENZYME) yields the potent vasoconstrictor octapeptide ANGIOTENSIN II; and then, via other enzymes, other angiotensins also involved in the hemodynamic-regulating RENIN-ANGIOTENSIN SYSTEM. Hypertensinogen,Renin-Substrate,SERPINA8,Proangiotensin,Renin Substrate Tetradecapeptide,Serpin A8,Renin Substrate,Tetradecapeptide, Renin Substrate
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor

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