The central effect of nicotine on cardiovascular regulation has been extensively studied. However, due to its unselective nature for nicotinic acetylcholine receptors (nAChR) the involvement of specific nAChRs at sites in the brain, in central nervous cardiovascular regulation remains unclear. The effects of intracerebroventricular (i.c.v.) and intracisternal (i.e.) injections of the a7 selective agonist, PSAB-OFP, and the a4p2 selective agonist, TC-2559, were investigated on blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) compared with nicotine, in the anaesthetised rats. PSAB-OFP and TC-2559 i.c.v. caused a delayed dose-related increase in BP and RSNA. When given i.e. the action was similar except the rise in BP was more immediate. The possibility that the pressor response was partly due to the agonists causing the release of the vasoconstrictor vasopressin into the circulation was tested by repeating the i.c.v. and i.e. injections of the agonists in the presence of a selective vasopressin Via antagonist. In the presence of Vi antagonist (i.v.), PSAB-OFP and TC-2559 (i.c.v.) now induced no change in BP or RSNA however i.e., the increase in BP and RSNA was delayed with TC-2559, while PSAB-OFP caused a decrease in BP and no change in RSNA. The cardiovascular effects of i.c.v. PSAB-OFP and TC-2559 in the presence of Vi receptor antagonist (i.c.v.) were also completely blocked. PSAB-OFP and TC-2559 (i.e.) in rats pre-treated with Vi antagonist (i.e.), no longer produced an increase in BP and RSNA. However, the delayed fall in BP caused by PSAB-OFP was potentiated. Nicotine i.c.v. caused a dose-related increase in BP and renal sympathoinhibition while i.e. the rise in BP was larger and now associated with a bradycardia. In the presence of Vj antagonist (i.v.), nicotine's (i.c.v.) cardiovascular effects were blocked however nicotine i.e. caused a decrease in BP, RSNA and HR. In the presence of Vi antagonist (i.c.v.), nicotine caused no change in RSNA, but BP still increased. In the presence of Vi antagonist (i.e.), nicotine i.e. induced a decrease in RSNA and HR, with no change in BP. This study indicates that activation of a4p2 and <x7 nAChRs in the hindbrain cause an increase in BP due to vasopressin release into the periphery, which is mediated by a central vasopressinergic pathway, possibly involving a pathway from the hindbrain to the PVN. Interestingly, the renal sympathoexcitation was also prevented by blocking Via receptors in the periphery as well as in the brain. A possible mechanism is discussed whereby vasopressin or its antagonist accesses the brain via the circumventricular organs and then indirectly influence the PVN, supra-medulla or supra-spinal vasopressin neurons influencing the renal sympathetic outflow. Nicotine also causes an increase in BP by vasopressin release into the periphery, by acting on nAChR in the forebrain and the hindbrain. Interestingly, the decrease in RSNA is still observed when in the presence of Vj antagonist, suggesting that the decrease in RSNA is partly mediated by an action of nicotine on nAChRs at sites in the hindbrain such as the NTS.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:639525 |
| Date | January 2007 |
| Creators | Moore, C. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1444883/ |
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