Investigation of the effects of IVth ventricular administration of the 5‐HT₂ agonist, 1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOI), on autonomic outflow in the anaesthetized cat

Abstract

1 The effects of IVth ventricular injections of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on renal, splanchnic and cardiac sympathetic nerve activities, phrenic nerve activity, arterial blood pressure, heart rate, femoral arterial conductance, tracheal and intragastric pressures were investigated in achloralose anaesthetized, neuromuscular blocked and artificially ventilated cats. 2 Cumulative doses of DOI (80, 160 and 320nmolkg-1) injected into the IWth ventricle caused an increase in mean arterial blood pressure, a fall in femoral arterial conductance, an increase in tracheal pressure and a decrease in the rate of phrenic nerve bursts but did not affect any of the other variables recorded. 3 Even after i.v. administration of the peripheral 5-HT2 antagonist BW501C67 (2 mg kg-1) following the highest dose of DOI there was still a significant pressor response, a fall in femoral arterial conductance and small increase in tracheal pressure. 4 In control experiments, intravenous infusion of noradrenaline to raise blood pressure to the levels obtained during the cumulative doses of DOI caused large falls in renal, splanchnic and cardiac nerve activities which were all significantly lower than those recorded during the cumulative doses of DOI. 5 The results of this study provide evidence for a brainstem site of action of DOI in producing hypertension and further support the hypothesis that central 5-HT2 receptors are involved in the control of skeletal muscle and skin vascular beds.

Involvement of central 5‐HT1A receptors in the reflex activation of pulmonary vagal motoneurones by inhaled capsaicin in anaesthetized cats

“…5-hydroxytryptamine (5-HT) causes an increase in tracheal pressure in anaesthetized cats implicating a role for central 5-HT receptors in the control of pulmonary vagal motoneurones. In this respect 5-HTIA and 5-HT2 receptors and 5-HT pathways are well known to play a role in the control of central respiratory drive (Lalley, 1986;King & Holtman, 1990;Shepheard et al, 1991;Sporton et al, 1991;Anderson et al, 1995) and in the control of cardiac vagal motoneurones, particularly 5-HTA receptors (Ramage & Fozard, 1987;Izzo et al, 1988;Bogle et al, 1990;Sporton et al, 1991;Chitravanshi & Calaresu, 1992;Futuro-Neto et al, 1993;. Hence the present experiments were carried out to investigate whether 5-HTA receptors play a role in the control of the reflex activation of pulmonary vagal motoneurones.…”

Comparison of the effects of IVth ventricular administration of some tryptamine analogues with those of 8‐OH‐DPAT on autonomic outflow in the anaesthetized cat

“…To give microinjections into the IVth ventricle the animal's head was placed in a stereotaxic frame and a cannula placed so that its tip lay in the IVth ventricle as described previously (Shepheard et al, 1991b). The position was confirmed at the end of the experiment by injecting pontamine sky blue dye (20 Isl over 1 min).…”

“…Arterial blood pressure, heart rate, body temperature and arterial blood gases and pH were monitored as previously described (Shepheard et al, 1991b). A constant infusion of a solution comprising 500ml plasma substitute (Gelofusine), 500 ml H20, 8.4 g NaHCO3 and 2 g of glucose was given at a rate of 6 ml kg-I h-' into the brachial vein to maintain blood volume and to counteract the development of non-respiratory acidosis.…”

“…The left phrenic nerve was exposed low down in the neck at the level of the 4th and 5th spinal nerves. Whole nerve activity was recorded from the intact nerves by use of bipolar silver hook electrodes as previously described (Shepheard et al, 1991b). In all experiments sympathetic nerve activity was tested to see if it was under baroreceptor modulation by checking that activity in the nerves increased during a fall in blood pressure induced by sodium nitroprusside (2 jig kg-', i.v.)…”

“…The outputs were then displayed on a Grass polygraph recorder and were calibrated in arbitrary units. Phrenic nerve activity was quantified by integrating the amplitude and frequency of the action potentials in each irL'piratory burst or, if continuous, by integrating the amount of activity in a 5 s period, again using a solid state electronic integrator, the output of which was displayed on the Grass polygraph in arbitrary units (see Shepheard et al, 1991b). The first method of quantifying phrenic nerve activity gives an indication of both the amount of activity in each inspiratory burst and the frequency of inspiratory bursts.…”