pituitrin and homocysteic-acid

Topics: Acetylcholine; Amino Acids; Animals; Aspartic Acid; beta-Alanine; beta-Endorphin; beta-Lipotropin; Biogenic Amines; Carnosine; Catecholamines; Dopamine; Endorphins; Enkephalins; Epinephrine; gamma-Aminobutyric Acid; Glutamates; Glycine; Gonadotropin-Releasing Hormone; Histamine; Homocysteine; Insulin; Nerve Tissue Proteins; Neurotensin; Neurotransmitter Agents; Norepinephrine; Olfactory Bulb; Oxytocin; Serotonin; Substance P; Synapses; Taurine; Thyrotropin-Releasing Hormone; Vasopressins; Vertebrates

In Wistar rats, an increase in renal sympathetic activity is induced by activation of presympathetic neurones in the paraventricular nucleus (PVN) and reflexly by a mild venous haemorrhage. Both stimuli are dependent on the release of vasopressin and glutamate at spinal synapses. The significance of the supraspinal pathway and the co-operative interaction of vasopressin with an excitatory amino acid is unclear. The present study examines this in Brattleboro rats, which have a natural vasopressin gene deletion. The responses were compared with Long-Evans rats, from which Brattleboro rats are derived. All rats were anaesthetized with a mixture of urethane (650 mg kg(-1) i.v.) and chloralose (50 mg kg(-1) i.v.). Recordings were made of blood pressure, heart rate and renal sympathetic nerve activity (RSNA). Microinjection of d,l-homocysteic acid (DLH, 0.2 m, 100 nl) at sites restricted to the PVN elicited significant increases in RSNA (P < 0.001) in both strains of rats. These changes were significantly reduced (P < 0.01) in Long-Evans rats by intrathecal application to the spinal cord of either a V(1a) antagonist or a glutamate antagonist (kynurenic acid), whereas in Brattleboro rats the changes were significantly reduced (P < 0.05) only by kynurenic acid. Removal of 1 ml of venous blood in Long-Evans rats increased RSNA by 28 +/- 4% (P < 0.01), which was significantly reduced (P < 0.05) by prior intrathecal application of either the V(1a) antagonist or by kynurenic acid. The same test in Brattleboro rats caused a significantly greater (P < 0.05) increase (63 +/- 14.7%) in RSNA which, in contrast to Long-Evans rats, was unchanged by intrathecal application of the V(1a) antagonist, being significantly reduced (P < 0.01) only by intrathecal kynurenic acid. Thus, in Brattleboro rats, the lack of vasopressin in the brain sympathetic pathways appears to be compensated, acutely, by glutamate-releasing pathways. This might indicate that, in normal rats, vasopressin is more important in maintaining longer term adjustments to stressors.

Topics: Animals; Blood Pressure; Excitatory Amino Acid Antagonists; Glutamic Acid; Heart Rate; Hemorrhage; Homocysteine; Kidney; Kynurenic Acid; Male; Neurons; Paraventricular Hypothalamic Nucleus; Rats; Rats, Brattleboro; Rats, Long-Evans; Spinal Nerves; Sympathetic Nervous System; Vasopressins

Neurones in the paraventricular nucleus of the hypothalamus project to rostral ventrolateral medullary spinally projecting vasomotor neurones. We studied the excitatory action and the role of glutamate and vasopressin in this pathway in anaesthetised rats. A five barrel micropipette assembly was used for extracellular recording of neuronal activity and for microiontophoresis of drugs into the vicinity of identified medullary vasomotor neurones. Iontophoresis of L-glutamate or vasopressin into the vicinity of a vasomotor neurone increased activity, effects which were blocked by simultaneous iontophoretic application of a glutamate receptor antagonist, or a vasopressin V(1a) antagonist respectively. Paraventricular neurones were activated either by microinjecting D,L-homocysteic acid or by disinhibition by microinjecting bicuculline. The excitatory effects on vasomotor neurones, of paraventricular nucleus stimulation at some sites were prevented by simultaneous microiontophoretic application of kynurenic acid or at other sites by application of V(1a) antagonist. Neither antagonist altered the ongoing activity of the vasomotor neurones. Therefore, glutamate or vasopressin may act as excitatory neurotransmitters at synapses of paraventricular neurones on rostral ventrolateral medullary vasomotor neurones.

Topics: Action Potentials; Animals; Antidiuretic Hormone Receptor Antagonists; Bicuculline; Cardiovascular Physiological Phenomena; Electric Stimulation; Evoked Potentials; Excitatory Amino Acid Antagonists; GABA Antagonists; Glutamic Acid; Homocysteine; Kynurenic Acid; Medulla Oblongata; Neural Pathways; Neurons; Paraventricular Hypothalamic Nucleus; Peptide Fragments; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Vasopressin; Spinal Cord; Synaptic Transmission; Vasopressins

Vasopressin may play an extrahypothalamic role in the central control of the cardiovascular system, specifically acting as a spinal neurotransmitter in the pathway where the paraventricular nucleus (PVN) alters sympathetic outflow. In this study, the effect of stimulating neuronal cell bodies in the PVN on renal sympathetic nerve activity (RSNA) and the possible involvement of vasopressin in the pathway was investigated in anesthetized rats. The PVN was stimulated by microinjection with 0.2 M D,L-homocysteic acid via a glass micropipette, and the hemodynamic and sympathetic responses were recorded. A computerized sympathetic peak-detection algorithm was applied to recordings of sympathetic discharges to retrieve information about the characteristics of RSNA during PVN stimulation. The algorithm scanned the series of RSNA voltages for significant increases followed by significant decreases in a small cluster of voltage values. Once each synchronized RSNA peak had been detected, its corresponding amplitude and peak-to-peak interval were calculated. PVN stimulation consistently increased the amplitude of RSNA (mean 30 +/- 5.6% over control), arterial pressure, and the peak-to-peak interval of discharges. A V1 vasopressin antagonist intrathecally administered as a 500-pmol dose was subsequently able to completely block the hemodynamic response (blood pressure increase of 14 +/- 5%) and a 35 +/- 6% increase in RSNA in response to PVN stimulation and intrathecal vasopressin. Thus spinal vasopressin is likely to be a neurotransmitter involved in the cardiovascular regulation involving the PVN.

Topics: Animals; Electric Stimulation; Electrophysiology; Glutamates; Glutamic Acid; Homocysteine; Injections, Spinal; Male; Paraventricular Hypothalamic Nucleus; Rats; Rats, Wistar; Sympathetic Nervous System; Vasopressins

Unilateral microinjection of L-glutamate (L-Glu, 0.5-5 nmol) into the locus coeruleus (LC) of rats anesthetized with chloralose elicited decreases in blood pressure and heart rate. The maximal depressor response elicited by injection of L-Glu into the LC was approximately 30 mmHg, and the maximal bradycardic response was approximately 35 bpm. Microinjections into the LC of DL-homocysteic acid (1 nmol) and carbachol (1 nmol), agents which (like L-Glu) stimulate neurons within the LC, also produced depressor and bradycardic responses. Vagal blockade with methyl atropine eliminated the bradycardic response, but had no effect on the decrease in arterial pressure elicited by stimulation of neurons within the LC. Destruction of the noradrenergic neurons of the LC by local administration of 6-hydroxydopamine eliminated the cardiovascular responses elicited by injection of L-Glu or carbachol into the LC. These results are in direct contrast to the pressor response elicited by electrical stimulation of the region containing the LC. Destruction of the LC with 6-hydroxydopamine, which totally eliminated the depressor response to L-Glu, slightly potentiated the pressor response elicited by electrical stimulation of this region. Electrical stimulation of the region containing the LC has also been reported to increase plasma vasopressin levels; this response could not be reproduced by by stimulation of the LC by microinjection of L-Glu. These results indicate that stimulation of the noradrenergic neurons of the rat LC decreases arterial pressure and heart rate. Furthermore, these results suggest that the pressor response elicited by electrical stimulation of this region is not due to stimulation of neurons of the LC.

Topics: Animals; Atropine; Blood Pressure; Carbachol; Cerebral Cortex; Electric Stimulation; Glutamates; Glutamic Acid; Heart Rate; Homocysteine; Hydroxydopamines; Locus Coeruleus; Male; Norepinephrine; Oxidopamine; Rats; Rats, Inbred Strains; Vasopressins