ROLE OF AREA POSTREMA IN TRANSGENE HYPERTENSION

Transgenic [Tg(+)] rats carrying the mouse Ren-2(d) gene [(mRen-2(d))2 7] are a newly established monogenetic form of experimental hypertensi on. To determine whether the area postrema contributes to the developm ent 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-lesione d Tg(+) rats, the increase in systolic blood pressure was significantl y attenuated in area postrema-lesioned Tg(+) rats. At 9 weeks of age, a femoral artery was cannulated for the measurement of arterial pressu re in awake rats. Mean arterial pressure (MAP) in area postrema-lesion ed Tg(+) rats was significantly (P<.01) lower than that in sham-lesion ed rats: 171+/-7 and 132+/-5 mm Hg, respectively. Baroreceptor reflex was evaluated by intravenous infusion of sodium nitroprusside. There w as no significant difference in baroreceptor reflex sensitivity betwee n the two groups. Intravenous pentolinium (5 mg/kg), used to produce s ympathetic ganglionic block, caused significant decreases in MAP in bo th groups. However, the reduction of MAP in the sham-lesioned group wa s significantly (P<.05) greater than that in the area postrema-lesione d group: -73+/-4 and -48+/-6 mm Hg, respectively. The ratio of left ve ntricular weight to body weight in sham-lesioned Tg(+) rats was signif icantly larger than that of area postrema-lesioned rats. These results suggest that ablation of the area postrema markedly attenuates the de velopment of hypertension in mRen-2(d) TX(+) rats, and this attenuatio n may be attributed to decrease in sympathetic outflow.