Gender Differences in Pressure-Natriuresis and Renal Autoregulation
Role of the Angiotensin Type 2 Receptor
Sexual dimorphism in arterial pressure regulation has been observed in humans and animal models. The mechanisms underlying this gender difference are not fully known. Previous studies in rats have shown that females excrete more salt than males at a similar arterial pressure. The renin-angiotensin system is a powerful regulator of arterial pressure and body fluid volume. This study examined the role of the angiotensin type 2 receptor (AT2R) in pressure-natriuresis in male and female rats because AT2R expression has been reported to be enhanced in females. Renal function was examined at renal perfusion pressures of 120, 100, and 80 mm Hg in vehicle-treated and AT2R antagonist-treated (PD123319; 1 mg/kg/h) groups. The pressure-natriuresis relationship was gender-dependent such that it was shifted upward in female vs male rats (P<0.001). AT2R blockade modulated the pressure-natriuresis relationship, shifting the curve downward in male (P<0.01) and female (P<0.01) rats to a similar extent. In females, AT2R blockade also reduced the lower end of the autoregulatory range of renal blood flow (P<0.05) and glomerular filtration rate (P<0.01). Subsequently, the renal blood flow response to graded angiotensin II infusion was also measured with and without AT2R blockade. We found that AT2R blockade enhanced the renal vasoconstrictor response to angiotensin II in females but not in males (P<0.05). In conclusion, the AT2R modulates pressure-natriuresis, allowing the same level of sodium to be excreted at a lower pressure in both genders. However, a gender-specific role for the AT2R in renal autoregulation was evident in females, which may be a direct vascular AT2R effect.
- Received November 4, 2010.
- Revision received November 22, 2010.
- Accepted November 29, 2010.
- © 2010 American Heart Association, Inc.