Role of AT1 receptors in area postrema on baroreceptor reflex in spontaneously hypertensive rats

Intravenous injection of angiotensin II type 1 (AT₁) receptor antagonist improves the baroreceptor reflex gain in spontaneously hypertensive rats (SHRs). To investigate the role of area postrema in the modulation of the baroreflex control by AT₁ receptor, the effects of intravenous injection of CV-11974 (AT₁ receptor antagonist) on the baroreflex control of renal sympathetic nerve activity (RSNA) and heart rate (HR) were examined in sham and area postrema-lesioned SHRs. The baseline mean arterial pressure was similar in both groups. However, baseline heart rate was significantly lower (p<0.01) in area postrema-lesioned SHR than in sham-lesioned SHR, 307±11 and 365±10 beats/min (bpm), respectively. Intravenous CV-11974 (0.05 mg/kg) significantly decreased mean arterial pressure; however, it did not change HR and RSNA in either group. Reflex changes in RSNA and HR were elicited by intravenous infusion of either phenylephrine or sodium nitroprusside before and after intravenous injection of CV-11974. Intravenous CV-11974 increased baroreflex control of RSNA (G_max; ?1.57±0.08 vs. ?1.92±0.12%/mmHg, p<0.05) and HR (G_max; ?0.54±0.12 vs. 1.25±0.24 bpm/mmHg, p<0.05) in sham-lesioned SHRs. However, intravenous CV-11974 failed to alter the baroreflex sensitivities in area postrema-lesioned SHRs. These results suggest that the area postrema does not play a crucial role in maintenance of high blood pressure in adult SHRs, and that the improvement of baroreflex control of RSNA and HR by intravenous CV-11974 is mediated via the area postrema in SHRs.