The central action of the 5-HT(2) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on cardiac inotropy and vascular resistance in the anaesthetized cat

1. Experiments were carried out to determine the effects of the application of the selective 5-HT(2) receptor agonist DOI intravenously (in the presence of the peripherally acting 5-HT(2) receptor antagonist, BW501C67, 1 mg kg(−1), i.v.) or to the `glycine sensitive area' of the ventral surface (30 μg each side) on the left ventricular inotropic (left ventricular dP/dt max) and vascularly isolated hindlimb responses in anaesthetized cats. For the ventral surface experiments, NMDA (10 μg each side) was applied to act as a positive control. In all experiments heart rate and mean arterial blood pressure were held constant to exclude any secondary effects caused by changes in these variables. 2. DOI (n=6) i.v or on the ventral surface had no effect on left ventricular dP/dt max but caused a significant increase in hindlimb perfusion pressure of 40±9 and 50±14 mmHg, respectively. Respiration was unaffected. NMDA (n=6), applied to the ventral surface, caused significant increases in both left ventricular dP/dt max and hindlimb perfusion pressure of 1950±349 mmHg s(−1) and 69±17 mmHg respectively, with no associated change in left ventricular end-diastolic pressure. The amplitude of respiratory movements increased. 3. It is concluded that activation of 5-HT(2) receptors at the level of the rostral ventrolateral medulla (RVLM) excites sympathetic premotor neurons and/or their antecedents controlling hindlimb vascular resistance but not those controlling the inotropic effects on the left ventricle

Highly H+-sensitive neurons in the caudal ventrolateral medulla of the rat

The ventral surface of the caudal ventrolateral medulla (cVLM) has been shown to generate intense respiratory responses after surface acid-base stimulation. With respect to their chemosensitive characteristics, cVLM neurons have been less studied than other rostral-most regions of the brainstem. The purpose of these experiments was to determine the bioelectric responses of cVLM neurons to acidic stimuli and to determine their chemosensitive properties. Using extracellular and microiontophoretic techniques, we recorded electrical activities from 117 neurons in an area close to the ventral surface of the cVLM in anaesthetised rats. All neurons were tested for their sensitivity to H+. The fluorescent probe BCECF was used to measure extracellular pH changes produced by the microiontophoretic injection of H+ in brainstem slices. This procedure provided an estimation of the local changes in pH produced by microiontophoretic H+ application in the anaesthetised rat. Neurons coupled to the respiratory cycle, R (n = 51), were not responsive to direct stimulation with H+. Sixty-six neurons that did respond to H+ stimulation were uncoupled from respiration, and identified as NR neurons. These neurons presented distinct ranges of H+ sensitivity. The neuronal sensitivity to H+ was mainly assessed by the slope of the stimulus-response curve, where the steeper the slope, the higher the H+ sensitivity. On this basis, NR neurons were classed as being either weakly or highly sensitive to H+. NR neurons with a high H+ sensitivity (n = 12) showed an average value of 34.17 ± 7.44 spikes s−1 (100 nC)−1 (mean ± s.d.) for maximal slope and an EC50 of 126.76 ± 33 nC. Suprathreshold H+ stimulation of highly sensitive NR neurons elicited bursting pattern responses coupled to the respiratory cycle. The bursting responses, which were synchronised with the inspiratory phase and the early expiratory phase of the respiratory cycle, lasted for several seconds before returning to the steady state firing pattern characteristic of the pre-stimulus condition. These NR neurons, which possess the capacity to detect distinct H+ concentrations in the extracellular microenvironment, are excellent candidates to serve in a chemoreceptor capacity in the caudal medulla