Awarded by ATS at SFN 1999

474.6 Abolition of cyanide-induced sympathoexcitation by selective lesion of bulbospinal catecholaminergic neurons.
A.M. SCHREIHOFER* and P.G. GUYENET Univ. of Virginia.
Cardiovascular regulation: central control III (POSTER)

The rostral ventrolateral medulla (RVLM) contains BS C1 adrenergic cells and non-CA neurons whose relative importance for the production of sympathetic vasomotor tone and cardiovascular reflexes remains unknown. In the present study we evaluate 2 sympathetic reflexes after selective lesions of BS CA neurons with the neurotoxin saporin-anti-dopamine beta hydroxylase (SAP-DBH). Rats received bilateral microinjections of SAP-DBH (42 ng/200nl/site) into the spinal cord centered at the intermediolateral cell column at T2 & T4 & T6 and were allowed to recover for 3-5 weeks. Arterial pressure (AP), heart rate (HR), and splanchnic nerve activity (SNA) were measured while the rats were chloralose-anesthetized, artificially ventilated, and paralyzed. Baseline AP and HR were comparable between control rats (n-7, 113 +/- 7 mmHg, 426 +/- 12 bpm) and lesioned rats (n=7, 123 +/- 4 mmHg, 448 +/- 7 bpm). In control rats stimulation of the carotid chemoreflex (100 micrograms/kg sodium cyanide, iv) produced a burst in SNA (266 +/- 26%) followed by inhibition (to 18 +/- 3% of base). In contrast, in the SAP-DBH-treated animals cyanide produced only an inhibition of SNA (to 33 +/- 7% of base). Mean AP responses mirrored the SNA responses. In contrast, the Bezold-Jarisch reflex was not diminished in the SAP-DBH-treated rats. Phenyl biguanide (5 micrograms/kg, iv) decreased AP (22 +/- 3 vs. 42 +/- 5 mmHg), SNA (85 +/- 4 vs. 67 +/- 6%), and HR (28 +/- 6 vs. 56 +/- 7 bpm) in control rats and lesioned rats respectively. Histological examination revealed that SAP-DBH depleted the vast majority of BS C1 cells (>70% of the rostral third of the C1 cell group), and >80% of the A5 cell group. These results indicate that sympathetic vasomotor tone persists and rats have a normal mean AP in the absence of most of BS C1 and A5 cells. Although the BS C1 cells may not be required for the Bezold-Jarisch reflex, BS CA cells are essential for the sympathoexcitatory response to cyanide. Work supported by NIH 28785.

Dr. Douglas Lappi, ATS and A.M. Schreihofer, University of Virginia

SFN 1999, Miami FLORIDA