Several lines of evidence implicate the median preoptic nucleus (MnPO) as a downstream site of activation following binding of angiotensin II (ANG II) at the subfornical organ and organum vasculosum of the lamina terminalis. We have shown previously that electrolytic lesion of the MnPO attenuated the increased blood pressure response to chronic intravenous infusion of ANG II. However, whether MnPO neurons or fibers that pass through this region contribute to this response is not clear. In the present study, to distinguish the relative importance of MnPO neurons from fibers of passage in the hypertensive response to chronic ANG II administration, male Sprague Dawley rats were randomly assigned to either sham (iSHAM) or ibotenic acid lesion of the MnPO (iMnPOx). In the iMnPOx group, 200 nl of ibotenic acid in phosphate buffer saline (5 μg/μl) was injected into each of 3 predetermined coordinates targeted at the entire MnPO. After a week of recovery, rats were instrumented with venous catheters, and radiotelemetric transducers for the intravenous administration of ANG II and the measurement of mean arterial pressure (MAP) and heart rate, respectively. Rats were given another week to recover. iSHAM and iMnPOx animals were then infused with saline (7 ml 0.9% NaCl/day) for 3 days as a control period, followed by 10 consecutive days of intravenous ANG II infusion (10 ng kg- 1 min- 1), and finally a recovery period similar to control. Throughout the protocol, a 0.4% NaCl diet and distilled water were provided ad libitum. By day 8 of ANG II infusion, MAP had increased 54 ± 2 mm Hg in iSHAM rats (n = 8). The hypertensive response to ANG II was significantly attenuated in the iMnPOx rats (n = 9), in which MAP had only increased 29 ± 3 mm Hg. These results support the hypothesis that neurons of the MnPO are involved in the central neural pathway mediating the chronic hypertensive effects of ANG II.
Bibliographical noteFunding Information:
T.P. is a recipient of a scholarship from the Anandamahidol Foundation. This work was supported by the National Heart Lung and Blood Institute grant RO1 HL-072180. The authors thank Dr. Thomas Cunningham for advice in ibotenic acid lesion technique, Dr. Anthony Tobias for statistical advice, and Dr. Al Beitz for graphical assistance.
- Angiotensin II
- Median preoptic nucleus
- Sympathetic nervous system