Abstract P033: PRESSOR, NATRIURETIC, AND RENAL RESPONSES IN ANGIOTENSIN II-INDUCED HYPERTENSION IN MALE AND FEMALE WILD-TYPE AND PROXIMAL TUBULE-SPECIFIC AT 1A RECEPTOR KNOCKOUT MICE

Dysregulation of intrarenal renin-angiotensin system is one of the key factors of human hypertension, but the mechanisms involved remain incompletely understood. To determine the roles of AT 1a receptors in the proximal tubules of the kidney, we infused angiotensin II (Ang II) for 2 weeks (40 ng / min, i.p.) in adult male and female wild-type C57BL/6J and mutant mice with deletion of AT 1a receptors in the proximal tubules (PT- Agtr1a -/- ), and treated with or without the AT 1 receptor blocker losartan (20 mg/kg/day, p.o.) (n=8 per group). The pressor response, 24 h urinary Na + excretion, glomerular and tubulointerstitial injury were compared between male and female wild-type and PT- Agtr1a -/- mice. Basal systolic, diastolic, and mean arterial blood pressure were about 13 ± 3 mmHg lower in male and female PT- Agtr1a -/- mice ( P Agtr1a -/- mice. In response to Ang II, both male and female wild-type and PT- Agtr1a -/- mice developed hypertension ( P Agtr1a -/- mice (n.s.). However, absolute blood pressure was about 12 ± 3 mmHg lower in male and female PT- Agtr1a -/- mice ( P Agtr1a -/- mice ( P Agtr1a -/- mice (n.s). Losartan did not increase the natriuretic responses further in all animals. Furthermore, Ang II-induced hypertension was associated with significant increases in glomerular and tubulointerstitial injury in male and female wild-type mice ( P Agtr1a -/- mice ( P Agtr1a -/- mice ( P 1 (AT 1a ) receptors in the proximal tubules of the kidney plays a key role in maintaining basal blood pressure homeostasis and overall body salt and fluid balance, and the development of Ang II-induced hypertension and kidney injury.