Gender difference in response to thromboxane A₂/prostaglandin H₂ receptor antagonism in spontaneously hypertensive rats

Background: Blood pressure (BP) is typically higher in men than in women. As in humans, BP is higher in male spontaneously hypertensive rats (SHRs) than in female SHRs. The mechanism(s) responsible for the higher BP in men and male rats has not been elucidated. Objective: The present study tested the hypothesis that thromboxane and/or the thromboxane A₂/prostaglandin H₂ receptor (TxR) plays a role in the gender difference in BP in SHRs. Methods: Male and female SHRs were treated with the TxR antagonist SQ29548 (2 μg/kg/min into the jugular vein) via minipump for 2 weeks; mean arterial pressure (MAP) and renal hemodynamic function were measured. To determine whether thromboxane played a role in the higher MAP in SHRs, male and female rats were treated with the thromboxane synthase inhibitor (TxI) furegrelate, 30 μg/kg/min, via minipump, for 2 weeks. Results: MAP was reduced with TxR antagonism in male but not in female SHRs. In addition, TxR antagonism in males caused renal vasodilation with increases in glomerular filtration rate and renal plasma flow, and reductions in renal vascular resistance. In contrast, MAP was not affected by the TxI in either males or females. Conclusion: These data support a role for TxR, but not thromboxane, in mediating the gender difference in BP in SHRs.