Sex differences in renal medullary endothelin receptor function in angiotensin II hypertensive rats

Hypertension. 2011 Aug;58(2):212-8. doi: 10.1161/HYPERTENSIONAHA.111.172734. Epub 2011 Jun 6.


We hypothesized that angiotensin (Ang) II hypertensive rats have impaired natriuresis after renal medullary endothelin (ET) B receptor stimulation that would be more evident in male versus female rats. Acute intramedullary infusion of the ET(B) agonist sarafotoxin 6c in normotensive male rats increased sodium excretion from 0.51±0.11 μmol/min during baseline to 1.64±0.19 μmol/min (P<0.05) after S6c. After 2 weeks of Ang II infusion (260 ng/kg per minute SC), male rats had an attenuated natriuretic response to S6c of 0.62±0.16 μmol/min during baseline versus 0.95±0.07 μmol/min after S6c. In contrast, ET(B)-dependent natriuresis was similar in female hypertensive rats (0.48±0.07 versus 1.5±0.18 μmol/min; P<0.05) compared with normotensive controls (1.05±0.07 versus 2.14±0.24 μmol/min; P<0.05). Because ET(A) receptors also mediate natriuresis in normotensive female rats, we examined ET(A) receptor function in female Ang II hypertensive rats. Intramedullary infusion of ET-1 increased sodium excretion in both hypertensive and normotensive female rats, which was partially blocked by the ET(A) antagonist BQ-123. Maximum ET(B) receptor binding in inner medullary membrane preparations was comparable between vehicle and Ang II hypertensive females; however, maximum ET(B) binding was significantly lower in male hypertensive rats (1952±251 versus 985±176 fmol/mg; P<0.05). These results indicate that renal ET(B) function is impaired in male Ang II hypertension attributed, at least in part, to a reduced number of ET(B) binding sites. Furthermore, renal ET receptor function is preserved in female rats during chronic Ang II infusion, suggesting that renal ET receptor function could serve to limit hypertension in females compared with males.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology
  • Animals
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Female
  • Hypertension / chemically induced
  • Hypertension / metabolism*
  • Hypertension / physiopathology
  • Kidney Medulla / drug effects
  • Kidney Medulla / metabolism*
  • Kidney Medulla / physiopathology
  • Male
  • Natriuresis / drug effects
  • Natriuresis / physiology
  • Rats
  • Receptors, Endothelin / metabolism*
  • Sex Characteristics*
  • Viper Venoms / pharmacology


  • Receptors, Endothelin
  • Viper Venoms
  • sarafotoxins s6
  • Angiotensin II