Blood pressure response to angiotensin II is enhanced in obese Zucker rats and is attributed to an aldosterone-dependent mechanism

Br J Pharmacol. 2012 Aug;166(8):2417-29. doi: 10.1111/j.1476-5381.2012.01953.x.


Background and purpose: Plasma aldosterone levels correlate positively with obesity, suggesting a link between the hypertension associated with obesity and increased mineralocorticoid levels. We tested the hypothesis that aldosterone is involved in the BP response to angiotensin II (AngII) in obese rats.

Experimental approach: Lean (LZR) and obese (OZR) Zucker rats were treated with AngII (9 µg·h(-1) ; 4 weeks), and BP and plasma AngII and aldosterone were determined.

Key results: Chronic AngII increased the BP in OZR markedly more so than in LZR. Plasma AngII levels in LZR and OZR were similar after AngII treatment. The AngII stimulated a rise in plasma aldosterone that was sixfold more in OZR than in LZR. The thickness of the zona glomerulosa of the adrenal glands was selectively increased by AngII in OZR. Adrenal mRNA levels of CYP11B2 aldosterone synthase and the AT(1B) receptor were selectively increased in AngII-treated OZR. The BP response to chronic AngII stimulation was diminished in OZR after adrenalectomy when plasma aldosterone was absent. Acute bolus injections of AngII did not increase the BP response or aldosterone release in OZR.

Conclusions and implications: The AngII-induced BP response is enhanced in obesity and this is associated with a specific increase in circulating aldosterone. Due to the AngII-induced growth of the zona glomerulosa in OZR, the AT(1B) receptors and aldosterone synthase may be selectively enhanced in obesity under concomitant AngII stimulation, increasing the adrenal synthesis of aldosterone. Our results confirm functionally that aldosterone plays a major role in obesity-related hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenalectomy
  • Aldosterone / metabolism*
  • Angiotensin II / pharmacology*
  • Animals
  • Blood Pressure / drug effects*
  • Hypertension / chemically induced*
  • Male
  • Obesity / metabolism*
  • Rats
  • Rats, Zucker


  • Angiotensin II
  • Aldosterone