Angiotensin II Pressor Activity Depends on Medial and Lateral Anterior Hypothalamic Pathways

Abstract

The preoptic region of hypothalamus was disconnected from caudal structures with two different-size knife cuts in rats to investigate the pathway responsible for the effects of intracerebroventricular (ICV) and intravenous (IV) angiotensin II (ang II) on blood pressure and arginine vasopressin (AVP) release. Seven days after surgery ICV ang II (125 ng) in sham-operated (sham) rats increased mean arterial pressure (MAP) (+23 ±3 mmHg) and decreased heart rate (HR) (-58 ± 5 beats/minute). However, ICV ang II had no effect on MAP or HR of rats with a large (preoptic-hypothalamic disconnection) cut. Both the pressor response (+12 ±2 mmHg) and the bradycardia (-39 ±6 beats/minute) were significantly reduced by a small (medial preoptic-hypothalamic disconnection) cut. The increased plasma AVP to ICV ang II in sham rats (9.8 ±3.6 pg/mL) was abolished in large-cut rats and attenuated in small-cut rats (3.2 ±0.7 pg/mL). IV bolus injection of ang II (125 ng) in sham rats increased MAP by 43 mmHg, whereas large-cut rats showed a blunted (25%) pressor response. The pressor response to IV infusion of ang II (8 ng/20 μL/minute for 15 minutes) was diminished in large-cut rats (+4 ±1 mmHg) as compared with that in sham rats (+ 19 ± 2 mmHg). Both cuts transected the projection between the periventricular tissue surrounding the anteroventral third ventricle and supraoptic nucleus, but the supraoptic-neurohy pophyseal pathway was severed only by the large cut. By examining the location of microknife cuts, the authors conclude that the connectivity of the preoptic region with more caudal sites is necessary for the expression of the central and peripheral pressor activity of ang II, probably involving a key role of supraoptic nucleus and its connections.