Anteroventral third ventricle lesions attenuate pressor responses to serotonin in anesthetized rats.
When administered intravenously, serotonin (5-hydroxytryptamine; 5-HT) evokes a triphasic blood pressure response, consisting of the Bezold-Jarisch-associated depressor response, a pressor action, and long-lasting depressor response. Because the pressor response may, in part, be caused by central nervous system (CNS) activation by 5-HT, we predicted that destruction of the anteroventral third ventricle (AV3V) region, an area rich in 5-HT receptors, would attenuate increases in blood pressure to intravenous 5-HT. In anesthetized sham-lesioned and AV3V-lesioned Sprague-Dawley rats, we measured mean arterial pressure (MAP), heart rate (HR), and lumbar sympathetic nerve activity (SNA) to increasing bolus doses of intravenous 5-HT (1, 2.5, 5, 10, 25 mu g/kg), before and after blockade of bradycardia using methylatropine (200 mu g/kg). In all rats, bolus injections of 5-HT elicited bradycardia accompanied by a fall in lumbar SNA and an initial hypotension followed by a pressor response and a longer lasting hypotensive response. The bradycardia, reduction in lumbar SNA, and both depressor responses were equivalent in sham-lesioned and AV3V-lesioned groups. Importantly, AV3V lesions attenuated pressor responses to increasing doses of 5-HT (3 +/- 1, 6 +/- 4, 6 +/- 4, 17 -/+ 4 35 +/- 3 mmHg) compared to sham-lesioned controls (6 +/- 3, 16 +/- 7, 33 +/- 5, 54 +/- 4, 51 +/- 6 mmHg; P < 0.0001). This attenuation was conserved following blockade of bradycardia with methylatropine (P < 0.01). In summary, pressor responses to intravenous 5-HT are diminished by AV3V lesions. These data indicate that the pressor component of the blood pressure response to intravenous 5-HT is partly dependent upon interaction with the CNS.
Muntzel
M S
MS
Department of Psychology, the Cardiovascular Center, University of Iowa, Iowa City 52242-1407, USA.
Lewis
S J
SJ
Johnson
A K
AK
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002552:Cerebral Ventricles / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*
D012701:Serotonin