RGD Reference Report - Reduction of cold-induced hypertension by antisense oligodeoxynucleotides to angiotensinogen mRNA and AT1-receptor mRNA in brain and blood. - Rat Genome Database

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Reduction of cold-induced hypertension by antisense oligodeoxynucleotides to angiotensinogen mRNA and AT1-receptor mRNA in brain and blood.

Authors: Peng, JF  Kimura, B  Fregly, MJ  Phillips, MI 
Citation: Peng JF, etal., Hypertension. 1998 Jun;31(6):1317-23.
RGD ID: 8549458
Pubmed: PMID:9622148   (View Abstract at PubMed)

Rats exposed chronically to mild cold (5 degrees C/41 degrees F) develop hypertension and cardiac hypertrophy. This provides a unique model of hypertension that is environmentally induced. The blood renin-angiotensin system (RAS) has been shown to play a role in both initiating and maintaining the high blood pressure (BP) in cold-induced hypertension. The mechanism also appears to involve both the tissue and brain RAS because there is increased mRNA for angiotensinogen (AGT) and angiotensin type 1 (AT1) receptors in brain and peripheral tissues, an increased spontaneous drinking response, and an increased dipsogenic response to acute administration of angiotensin II (Ang II) in cold-treated rats. Antisense oligodeoxynucleotides (AS-ODN), targeted to the RAS, have been shown to reduce BP in spontaneously hypertensive rats. Therefore, we injected AS-ODN in rats with cold-induced hypertension to test whether antisense inhibition was effective in reducing this nongenetic nonsurgical hypertension. Sprague-Dawley rats were made hypertensive by cold exposure and injected intracerebroventricularly with AS-ODN to AGT mRNA (n=6) or AT1 receptor mRNA (n=6). Systolic BP was recorded by tail cuff 24 hours later for 2 or 7 days, respectively. Systolic BP decreased significantly in response to AGT-AS-ODN (40+/-6 mm Hg, P<0.01) within 1 day after injection and to AT1 receptor-AS-ODN (P<0.05) for 3 days after injection. The maximum decrease was 41+/-10 mm Hg. Systolic BP then gradually increased to the preinjection level. The spontaneous drinking response to cold treatment also decreased significantly (P<0.05) after AGT-AS-ODN or AT1 receptor-AS-ODN intracerebroventricular injection. Intracardiac injection of AT1-AS-ODN (n=6) reduced systolic BP by 36+/-8 mm Hg (P<0.05) and decreased AT1 receptor as measured by autoradiography in aorta, adrenal glands, and kidneys 24 hours after injection. These data show that AS-ODN reduces BP in cold-induced hypertension and that the hypertension involves both peripheral tissues and central RAS in addition to blood-borne RAS mechanisms.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AGTHumanhypertension  ISOAgt (Rattus norvegicus) RGD 
AGTR1Humanhypertension  ISOAgtr1a (Rattus norvegicus) RGD 
AgtRathypertension  IMP  RGD 
AgtMousehypertension  ISOAgt (Rattus norvegicus) RGD 
Agtr1aRathypertension  IMP  RGD 
Agtr1aMousehypertension  ISOAgtr1a (Rattus norvegicus) RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AgtRatangiotensin-mediated drinking behavior  IMP  RGD 
Agtr1aRatdrinking behavior  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Agt  (angiotensinogen)
Agtr1a  (angiotensin II receptor, type 1a)

Genes (Mus musculus)
Agt  (angiotensinogen)
Agtr1a  (angiotensin II receptor, type 1a)

Genes (Homo sapiens)
AGT  (angiotensinogen)
AGTR1  (angiotensin II receptor type 1)


Additional Information