Sex differences in the renal vascular response to angiotensin II involves the Mas receptor.

Aim The renin-angiotensin system ( RAS) depressor arm, particularly renal angiotensin type 2 receptor ( AT2 R) and Mas receptor (mas R) expression, is enhanced in females, which may contribute to renal and cardiovascular protection. We examined the hypotheses that mas R activation increases renal blood flow ( RBF) at rest and attenuates the reduction in RBF in response to angiotensin II (Ang II) infusion in female rats. Furthermore, we postulated that combined activation of the AT2 R and mas R would produce a greater response than mas R activation alone. Methods In anaesthetized male and female Wistar rats, mean arterial pressure ( MAP) and RBF responses during graded Ang II infusion (30-1000 ng kg−1 min−1 i.v.) were assessed following pre-treatment with vehicle, the mas R antagonist A779, or A779 plus the AT2 R antagonist PD123319. Results Basal MAP was not altered by any pre-treatment. Basal RBF decreased approx. 20% in female ( P < 0.05), but not male rats in response to A779. However, basal RBF was not altered by A779 + PD123319. Ang II infusion reduced RBF in a dose-related fashion ( Pdose < 0.0001) and mas R blockade did not alter the RBF response to Ang II infusion in male or female rats. However, A779 + PD123319 attenuated the reduction in RBF response to Ang II in females ( Pgroup < 0.005), but not males. Conclusion The impact of the mas R on renal haemodynamics appears to be sexually dimorphic, with greater effects in female than male rats. However, the paradoxical effects of dual AT2 R and mas R blockade suggest that a greater understanding of the complex interactions between RAS components is required before the therapeutic opportunities of AT2 R and/or mas R stimulation can be advanced. [ABSTRACT FROM AUTHOR]