Obese female SHHF/Mcc-facp rats resist antihypertensive effects of renin-angiotensin system inhibition

L. C. Sharkey, B. J. Holycross, S. A. McCune, M. J. Radin, M. Judith Radin

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Gender and obesity may influence response to pharmacological modulation of the renin-angiotensin system. We used SHHF/Mcc-facp rats to study effect of obesity and gender on the ability of an AT1 receptor antagonist to decrease blood pressure. After 2 weeks treatment with irbesartan (50 mg/kg), only lean and obese males showed significant decreases in blood pressure, while obese females were completely resistant. Lean females showed a trend toward lowering of pressure (p=0.06). However, irbesartan similarly shifted angiotensin II dose response curves to the right in all groups. Twelve weeks of irbesartan also failed to decrease blood pressure, but did significantly reduce heart weight in obese females. In untreated rats, obese females had lower plasma renin activity and serum angiotensin converting enzyme activity compared to lean males, while lean and obese females had increased urinary endothelin excretion. Despite an otherwise similar genetic background contributing to hypertension and heart failure, obese females have different patterns of humoral activation compared to lean males, which may contribute to their resistance to the depressor effects of irbesartan.

Original languageEnglish (US)
Pages (from-to)227-239
Number of pages13
JournalClinical and Experimental Hypertension
Issue number3
StatePublished - 2001

Bibliographical note

Funding Information:
This study was supported in part by a grant from Bristol-Myers Squibb/Sanofi. This work also was supported in part by grants from the Central Ohio Diabetes Association and the US Public Health Service (HL48835). Salaries and research support were provided in part by state and federal funds appropriated to the Ohio Agricultural Research and Development Center, Ohio State University.


  • Angiotensin receptor blockers
  • Endothelin
  • Female
  • Hypertension
  • Obesity
  • Renin-angiotensin system
  • SHHF/Mcc-fa rats


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