P 38 Proteinase activated receptor 2 (PAR2) on blood pressure and electrolyte handling in the normal pregnant rat

Objectives Healthy pregnancy is characterized by avid aldosterone-mediated renal sodium retention driving a ∼40% plasma volume expansion in the presence of decreased or normal blood pressure. Incredibly, gestational potassium retention occurs in the face of this high circulating aldosterone, decreased renal NCC abundance/ phosphorylation, and increased renal ENaC activity, all of which are potent kaliuretic factors. The mechanisms permitting these opposing adaptations are largely unknown. Research in non-pregnant rats has shown that activation of proteinase activated receptor type 2 (PAR2) can produce vasodilation, inhibit potassium secretion via the renal outer medullary potassium channel (ROMK) in principal cells, and stimulate thiazide sensitive sodium chloride reabsorption (pendrin/NDCBE-mediated) in intercalated cells of the cortical collecting duct. Here, we investigate renal PAR2 activation in virgin and normal pregnant rats. Methods We measured the mRNA expression of PAR2 in the renal cortex, outer medulla, and inner medulla of virgin (V), mid- (MP), and late pregnant (LP) rats using quantitative real-time PCR. We also measured in vivo blood pressure (BP), natriuretic, and kaliuretic responses to 0.1 mg/kg, 0.3 mg/kg, and 1 mg/kg doses of PAR2 agonist peptide (SLIGRL-NH2) in anesthetized V and LP rats. Results We found that PAR2 mRNA was increased in the inner medulla of MP and LP rats. We also found that LP rats had larger decreases in BP compared to baseline than V rats at 0.1 and 0.3 mg/kg doses of agonist peptide. LP rats also had increased net sodium retention compared to virgin rats following 0.3 mg/kg and 1 mg/kg agonist peptide, but decreased net potassium retention compared to virgins with all doses. Conclusions PAR2 mRNA (an index of activity) is increased in the pregnant rat and activation of this receptor causes larger decreases in BP and increases in sodium retention compared to virgin controls. Further studies will determine the mechanism involved as well as the physiological role of increased renal PAR2 in pregnancy.