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Many studies have demonstrated that the ventrolateral medulla (VLM) plays an important role in the maintenance of systemic arterial pressure (SAP) and vascular tone. The VLM is divided into rostral (RVLM) and caudal (CVLM) portions which play opposing roles in regulating cardiovascular functions. The purposes of this study are to explore the relationship of fibers projecting between the RVLM and CVLM, and to investigate the effect of propofol (PPF, 2 mg/kg), an anesthetic agent, on modulating their neuronal firing rate (NFR). Forty-four adult cats were anaesthetized intraperitoneally with urethane (400 mg/kg) and alpha-chloralose (40 mg/kg). The femoral artery was cannulated to allow monitoring of SAP and heart rate (HR). The femoral vein was cannulated for intravenous drug administration. Microinjection of glutamate (Glu, 3.0 nmol/30 nl), kynurenic acid (Kyn, 3.0 nmol/30 nl), gamma-aminobutyric acid (GABA, 4.0 nmol/30 nl), or bicuculline (Bicu, 4.0 nmol/30 nl) into the RVLM produced SAP increases or decreases, but did not significantly change the NFR in the CVLM. This occurred even after intravenous administration of PPF. This shows that there are few fiber projections from the RVLM to the CVLM. Conversely, microinjection of Glu, Kyn, GABA or Bicu into the CVLM produced SAP changes, and the NFR in the RVLM was significantly changed. These changes were more significant after intravenous administration of PPF. These results show that there are more fibers projecting from the CVLM to the RVLM and fewer fibers projecting from the RVLM to the CVLM to affect the SAP and its NFR.

Nitric oxide (NO) is synthesized from L-arginine by NO synthase (NOS). NO stimulates the soluble form of guanylyl cyclase (sGC) and induces accumulation of cyclic guanosine monophosphate (cGMP). The purpose of this study was to examine whether the cardiovascular responses induced by N-methyl-D-aspartate (NMDA) in the rostral ventrolateral medulla (RVLM) depend on the actions of NOS and sGC. In anesthetized cats, the extracellular NO level was measured by in vivo voltammetry using a nafion/porphyrine/o-phenylenediamine-coated carbon-fiber electrode. Microinjection of NMDA into the RVLM produced hypertension and bradycardia associated with NO formation. These NMDA-induced responses were attenuated by prior injections of 7-nitroindazole, a neuronal NO synthase (nNOS) inhibitor, and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a sGC inhibitor. These findings suggest that NO is involved in the NMDA-induced cardiovascular responses in the RVLM.

The effect of propofol on neuronal activity in the rostral ventrolateral medulla (RVLM) is not well established. Therefore, we performed extracellular recording on neurons of the RVLM to investigate neuronal activity before and after administration of intravenous propofol. The mean systemic arterial pressure (MSAP), heart rate and integrated neuronal firing rate (INFR) in the RVLM were continuously recorded in anesthetized cats before and after intravenous injection of 2 mg/kg propofol or supplemental injections of 1, 2 and 4 mg/kg propofol that were given respectively. Additionally, we compared the MSAP, heart rate (HR), and INFR in the RVLM following intravenous injection of 2 mg/kg propofol or 12.5 microg/kg nitroprusside. Neuronal firing was dose-dependently and reversibly inhibited after the supplemental doses of 1, 2 and 4 mg/kg propofol. The control INFR was 14.2 +/- 9.9 Hz, and this decreased to 12.1 +/- 9.4 Hz after the first dose of propofol (P = 0.085 vs. control), and further decreased to 9.3 +/- 7.7 Hz (P = 0.001 vs. control) and 7.5 +/- 7.7 Hz (P0.001 vs. control) after the second and third doses of propofol, respectively. Besides, SAP and HR were dose-dependently decreased by propofol as well. However, the effects of propofol and nitroprusside on neuronal activity in the RVLM differed. Propofol inhibited neuronal firing, whereas nitroprusside activated neuronal firing. In conclusion, propofol may dose-dependently inhibit spontaneous neuronal activity and the baroreflex in the RVLM.

We examined the effects of serotonin (5-HT) on cardiovascular responses and blood flows in the right common carotid artery (RCCA), superior mesenteric artery (SMA) and right femoral artery (RFA), stimulated by glutamate (Glu) in the dorsomedial medulla (DM), rostral ventrolateral medulla (RVLM) and caudal ventrolateral medulla (CVLM). Microinjection of Glu into the DM produced increases in systemic arterial pressure (SAP) and flows in the RCCA and RFA, and decrease in flow in the SMA. Microinjection of Glu into the RVLM produced increases in SAP and decreases in flows in the RCCA, SMA and RFA. Prior microinjections of 5-HT into the same sites attenuated all the Glu-induced responses. Microinjection of Glu into the CVLM produced decreases in SAP and flows in the RCCA, SMA and RFA. These decreases were potentiated by prior injection of 5-HT. These findings suggest that 5-HT modulates the cardiovascular and blood flow responses induced by Glu in the medulla.

Using in vivo voltammetry to directly measure extracellular nitric oxide (NO) levels, our previous studies suggested that the neuronal NO synthase (nNOS) and cyclic guanosine monophosphate (cGMP) signal transducing systems are involved in the cardiovascular responses elicited by activation of N-methyl-D-aspartate (NMDA) receptors in the rostral ventrolateral medulla. In this study, we examined if the depressor responses elicited by activation of NMDA receptors in the caudal ventrolateral medulla (CVLM) also depend on the actions of nNOS and soluble guanylyl cyclase. In anesthetized cats, microinjection of NMDA into the CVLM produced hypotension and bradycardia associated with NO formation. These NMDA-induced responses were attenuated by prior injections of 2-amino-5-phosphonopentanoate (a NMDA receptor competitive antagonist), 7-nitroindazole (a nNOS inhibitor) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (an inhibitor of soluble guanylyl cyclase). These findings suggest that NO is also involved in the NMDA-induced depressor responses of the CVLM.

SUMMARY 1. The purpose of the present study was to investigate the effect of bilateral common carotid artery occlusion (BCCAO) on cardiovascular responses and nitric oxide (NO) formation in the nucleus tractus solitarius (NTS). 2. Twenty-three adult cats were anaesthetized intraperitoneally with urethane (400 mg/kg) and α-chloralose (40 mg/kg). The femoral artery was cannulated to allow monitoring of systemic arterial pressure (SAP) and heart rate (HR). The femoral vein was cannulated for intravenous drug administration. 3. Extracellular NO levels in the NTS were measured by in vivo voltammetry using an NO microsensor combined with a microcomputer-controlled apparatus. 4. Microinjection of l-arginine (30 nmol) into the NTS produced hypotension and NO release. This effect of l-arginine was not changed by 2 min of BCCAO. 5. Bilateral common carotid artery occlusion produced increases in SAP and NO levels. These effects were more apparent in vagotomized than in intact animals. 6. The onset latency of BCCAO-induced changes in SAP levels (8.4 ± 2.5 s) was longer than that for changes in NO (4.7 ± 1.7 s). 7. Bilateral common carotid artery occlusion induced hypertension and NO release in the NTS of intact and vagotomized animals. These cardiovascular and NO responses to BCCAO were significantly attenuated by NG-nitro-l-arginine methyl ester (10 mg/kg, i.v.) and MK-801 (2.5 mg/kg, i.v.). These data suggest that NO synthase and activation of N-methyl-d-aspartate receptors are involved in the cardiovascular and NO responses to BCCAO.

Propofol may cause hypotension and the mechanism is complex. The present study was designed to determine the direct actions of propofol in medulla of cats. Mean systemic arterial pressure (MSAP), heart rate (HR) and cardiac contractility (dp/dt) were compared before and after administration of propofol through the femoral vein (2, 3 or 4 mg · kg−1), vertebral artery (1 mg · kg−1) or the lateral cerebral ventnricle (0.5 mg · kg−1) in eight anaesthetized cats. To study the direct effect of propofol in medulla, pressor areas of the dorsomedial medulla (DM) and rostral ventrolateral medulla (RVLM), or the depressor area of the caudal ventrolateral medulla (CVLM) were first identified with electrical stimuli and then confirmed by pressure microinjection of glutamate (Glu, 0.25M, 30 nl) via a multibarrel-micropipette in 28 cats. One hour later, propofol (0.001%, 50 nl) was microinjected at the same site. Electrical stimulation and Glu were applied again to compare changes of SAR HR and dp/dt with that of the control. Propofol dose-dependently decreased SAR HR and cardiac contractility. The percent increase of MSAP induced by Glu were reduced by propofol in DM (59 ± 3 % vs 13 ± 2 %, n = 11.P 0.05). Our results show that propofol principally inhibits the vasomotor mechanism in the dorsomedial and ventrolateral medulla to effect its hypotensive actions. Nos resultats montrent que l’action hypotensive du propofol est causee par l’inhibition du mecanisme vasomoteur au niveau des zones bulbaires dorsomediane et ventrolaterale.