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(Hypertension. 2003;41:657.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Gender Differences in ET and NOS Systems in ET_B Receptor–Deficient Rats

Effect of a High Salt Diet

From the Department of Pharmacology and Toxicology (T.A.T., J.S.P.), Vascular Biology Center (D.M.P., J.S.P.), and Department of Surgery (D.M.P.), Medical College of Georgia, Augusta, Ga; and the Department of Pediatrics, University of Michigan (C.E.G.), Ann Arbor.

Correspondence to Jennifer S. Pollock, Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912. E-mail jpollock{at}mail.mcg.edu

The purpose of this study was to determine if rats lacking the ET_B receptor have altered renal endothelin (ET) production and NO synthase (NOS) activity in response to high salt and if female rats are better able to control blood pressure through higher NOS activity in rats heterozygous (sl/+) and homozygous (sl/sl) for ET_B receptor deficiency. On normal salt (0.4% NaCl; NS), male sl/sl rats had higher systolic blood pressures compared with male sl/+ and female sl/+ and sl/sl rats. On a high salt diet (10% NaCl; HS), blood pressure in male sl/+ rats was significantly higher than female sl/+ rats. However, ET_B receptor deficiency caused much larger increases in blood pressure in male and female rats. On NS, urinary ET excretion was not different between male and female of either genotype. HS significantly increased ET excretion in male and female sl/+ rats, but the increase was significantly less in sl/sl compared with sl/+. Homogenates of inner medullary collecting duct tissue were separated into particulate and cytosolic fractions and total NOS activity measured by conversion of [³H]L-arginine to [³H]L-citrulline. Female rats had significantly greater cytosolic NOS activity compared with male rats on NS. On HS, cytosolic NOS activity was lower in all groups compared with NS rats, whereas particulate NOS activity was significantly greater in male and female sl/+ rats compared with male and female sl/sl rats. These data support our hypothesis that NOS protects against rises in blood pressure in female rats and ET_B receptors prevent further increases in blood pressure due to increases in renal ET production and NOS activity.

Key Words: gender • hypertension, renal • sodium, dietary • nitric oxide synthase • receptor, endothelin

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