Role of area postrema in transgene hypertension

David B. Averill, Kiyoshi Matsumura, Detlev Ganten, Carlos M. Ferrario

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Abstract

Transgenic [Tg(+)] rats carrying the mouse Ren-2(d) gene [(mRen-2(d))27] are a newly established monogenetic form of experimental hypertension. To determine whether the area postrema contributes to the development of hypertension in mRen-2 Tg(+) rats, this circumventricular organ in the fourth ventricle was removed from 5-week-old Tg(+) rats. From weeks 4 through 9, systolic blood pressure was measured weekly by tail-cuff plethysmography in area postrema-lesioned and sham-lesioned Tg(+) rats. Although systolic blood pressure rose markedly in sham-lesioned Tg(+) rats, the increase in systolic blood pressure was significantly attenuated in area postrema-lesioned Tg(+) rats. At 9 weeks of age, a femoral artery was cannulated for the measurement of arterial pressure in awake rats. Mean arterial pressure (MAP) in area postrema-lesioned Tg(+) rats was significantly (P < .01) lower than that in sham-lesioned rats: 171 ± 7 and 132 ± 5 mm Hg, respectively. Baroreceptor reflex was evaluated by intravenous infusion of sodium nitroprusside. There was no significant difference in baroreceptor reflex sensitivity between the two groups. Intravenous pentolinium (5 mg/kg), used to produce sympathetic ganglionic block, caused significant decreases in MAP in both groups. However, the reduction of MAP in the sham-lesioned group was significantly (P < .05) greater than that in the area postrema-lesioned group: -73 ± 4 and -48 ± 6 mm Hg, respectively. The ratio of left ventricular weight to body weight in sham-lesioned Tg(+) rats was significantly larger than that of area postrema-lesioned rats. These results suggest that ablation of the area postrema markedly attenuates the development of hypertension in mRen-2(d) Tg(+) rats, and this attenuation may be attributed to decrease in sympathetic outflow.

Original languageEnglish
Pages (from-to)591-597
Number of pages7
JournalHypertension
Volume27
Issue number3 II
Publication statusPublished - Mar 1 1996

All Science Journal Classification (ASJC) codes

  • Internal Medicine

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    Averill, D. B., Matsumura, K., Ganten, D., & Ferrario, C. M. (1996). Role of area postrema in transgene hypertension. Hypertension, 27(3 II), 591-597.