title: Salt-sensitive hypertension after exposure to angiotensin is associated with inability to upregulate renal epoxygenases.
abstract: The current study was designed to determine whether angiotensin II infusion could lead to persistent salt-sensitive hypertension and to examine involvement of renal microvascular epoxygenases in this process. Six groups were studied: rats maintained on a normal salt diet for 4 weeks (NS); rats maintained on a high salt diet for 4 weeks (HS); and all other animals receiving angiotensin II (ANG) infusion and being fed a normal or high salt diet for 2 weeks; then the angiotensin II infusion was stopped and diets were either maintained or switched (ANG/NS-NS, ANG/NS-HS, ANG/HS-HS, ANG/HS-NS). Angiotensin II infusion resulted in a rise in blood pressure and an increase in urinary albumin excretion over the 2-week period. After angiotensin II withdrawal, blood pressure returned to normal in animals receiving a normal salt diet from weeks 2 to 4 (ANG/NS-NS and ANG/HS-NS groups). In contrast, blood pressure remained elevated in the group maintained on a high salt diet throughout the entire 4-week period (ANG/HS-HS group). Renal microvascular CYP2C11 and CYP2C23 protein levels were decreased by 50% to 60% in the ANG/HS-HS group compared with the NS group. Likewise, renal microvascular CYP2J protein was significantly decreased in the ANG/HS-HS group versus the NS group. Renal microvascular CYP2C11 and CYP2C23 mRNA levels were reduced in the ANG/HS-HS group compared with both the NS and HS groups. These results support the hypothesis that angiotensin II infusion induces persistent salt-sensitive hypertension after withdrawal of angiotensin II that may be due to downregulation of CYP2C and CYP2J epoxygenases in renal microvessels.
authors.affiliation: Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912-2500, USA.
authors.forename: Xueying
authors.initials: X
authors.lastname: Zhao
authors.forename: David M
authors.initials: DM
authors.lastname: Pollock
authors.forename: Darryl C
authors.initials: DC
authors.lastname: Zeldin
authors.forename: John D
authors.initials: JD
authors.lastname: Imig
mesh_terms: D000284:Administration, Oral; D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D001794:Blood Pressure; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D000072467:Cytochrome P450 Family 2; D006973:Hypertension / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply / Q000201:enzymology*; D008297:Male; D008833:Microcirculation / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000008:administration & dosage*; D039181:Steroid 16-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C000717351:Cyp2c23 protein, rat; D012333:RNA, Messenger; D000804:Angiotensin II; D012965:Sodium Chloride; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; D000090762:Cytochrome P-450 CYP2J2; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase