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(Hypertension. 2003;42:775.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Salt-Sensitive Hypertension After Exposure to Angiotensin Is Associated With Inability to Upregulate Renal Epoxygenases

Xueying Zhao; David M. Pollock; Darryl C. Zeldin; John D. Imig

From the Vascular Biology Center (X.Z., D.M.P., J.D.I.), the Department of Physiology (J.D.I.), and the Department of Surgery (D.M.P.), Medical College of Georgia, Augusta; and the Division of Intramural Research (D.C.Z.), National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC.

Correspondence to John D. Imig, PhD, Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912-2500. E-mail jdimig{at}mail.\|[mgr ]\|g.edu

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.

Key Words: endothelium-derived factors • hypertension, sodium-dependent • angiotensin II • kidney • vessels

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