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 (Gmax; -1.57 +/- 0.08 vs. -1.92 +/- 0.12%/mmHg, p < 0.05) and HR (Gmax; -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.
Matsumura
K
K
Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA. matsumk@intmed2.med.kyushu-u.ac.jp
Averill
D B
DB
Ferrario
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CM
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000294:innervation; D020547:Lateral Ventricles / Q000033:anatomy & histology / Q000502:physiology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; C081643:candesartan