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: Xueying Zhao, David M Pollock, Darryl C Zeldin, John D Imig
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 42 Issue 4 Pg. 775-80 (Oct 2003) ISSN: 1524-4563 [Electronic] United States
• PMID: 12900436 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cyp2c23 protein, rat
• RNA, Messenger
• Angiotensin II
• Sodium Chloride
• Cytochrome P-450 Enzyme System
• Aryl Hydrocarbon Hydroxylases
• CYP2C11 protein, rat
• Cytochrome P-450 CYP2J2
• Cytochrome P450 Family 2
• Steroid 16-alpha-Hydroxylase

Topics

• Administration, Oral
• Angiotensin II (toxicity)
• Animals
• Aryl Hydrocarbon Hydroxylases (genetics, metabolism)
• Blood Pressure
• Cytochrome P-450 CYP2J2
• Cytochrome P-450 Enzyme System (genetics, metabolism)
• Cytochrome P450 Family 2
• Hypertension (enzymology, etiology, physiopathology)
• Kidney (blood supply, enzymology)
• Male
• Microcirculation (enzymology)
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Sodium Chloride (administration & dosage)
• Steroid 16-alpha-Hydroxylase (genetics, metabolism)
• Up-Regulation