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Biomedical subjects

L C Weaver

Publications and source records attributed to L C Weaver.

At least 73 records · Page 4Linked to original sources
PubMed1991

Evidence for descending tonic inhibition specifically affecting sympathetic pathways to the kidney in rats.

1. The present study investigated the possibility that pre- and postganglionic neurones innervating the kidney and spleen in rats are affected by descending inhibitory as well as descending excitatory influences. This hypothesis was tested by comparing the effects of cervical spinal cord transection to the effects of blockade of tonic activity of excitatory neurones in the rostral ventrolateral medulla (RVLM). 2. Electrical discharge of multifibre postganglionic renal and splenic and preganglionic greater splanchnic nerves and 13th thoracic (T13) white rami was recorded in artificially respired, urethane-anaesthetized rats. In one group of rats, descending supraspinal pathways were interrupted by cervical spinal cord transection. In another group, tonic activity of rostral ventrolateral medulla (RVLM) neurones was blocked by bilateral microinjections of the inhibitory amino acid glycine. The effects of spinal cord transection were compared to effects of this bilateral RVLM blockade and to effects of unilateral RVLM blockade described in a previous study. 3. Spinal cord transection caused decreases in preganglionic greater splanchnic and postganglionic splenic nerves which were of the same magnitude as those caused by bilateral blockade of the RVLM. 4. In contrast, discharge of renal nerves was decreased more by bilateral RVLM blockade than by cervical spinal cord transection. Similarly, even unilateral RVLM blockade caused greater decreases in discharge of T13 white rami than were caused by spinal cord transection. 5. These findings suggest that renal nerves and their preganglionic inputs (T13 white rami) are controlled in part by tonic sympathoinhibitory influences which can be unmasked by blockade of the RVLM. These sympathoinhibitory influences do not appear to affect the activity of splanchnic and splenic nerves.

Adrenergic Fibers↗
PubMed1991

Differential control of renal and splenic nerves without medullary topography.

A previous study in our laboratory showed that pharmacological blockade of neurons in the rostral ventrolateral medulla has greater influence on the electrical activity of renal than splenic nerves (K. Hayes and L. C. Weaver, J. Physiol. Lond. 428: 371-385, 1990). This differential control of sympathetic nerves innervating different organs may be due to viscerotopic representation of the kidney and spleen within medullary neurons that control the vasculature. To search for this topographical organization, 15 nl (2.5 nmol) of the excitatory amino acid DL-homocysteic acid (DLH) was microinjected into the ventrolateral medulla (VLM) of rats anesthetized with urethan. No distinct viscerotopic organization was found in the rostral or caudal VLM. However, renal nerve responses were consistently greater than splenic by a fixed proportion. In summary, stimulation of rostral and caudal VLM neurons causes differential renal and splenic excitatory responses, but mechanisms providing this selective control do not involve spatial organization of neuronal groups in the VLM.

Animals↗
PubMed1991

Areas of rostral medulla providing tonic control of renal and splenic nerves.

The objective of this study was to determine whether nonuniform control of tonic discharge of renal and splenic nerves by the rostral ventrolateral medulla (RVLM) is dependent on viscerotopic representation of the kidney and the spleen in this region. Small (15 nl, 13 pmol) injections of the potent tau-aminobutyric acid agonist muscimol were used to map the RVLM of anesthetized rats, searching for areas that selectively provided tonic excitation of renal or splenic nerves. Most of the muscimol microinjections produced depressor responses and inhibition of sympathetic nerve activity. Activity of renal nerves was inhibited significantly more than that of splenic nerves, but we found no evidence for topographical organization of RVLM influences on tonic activity of these two nerves. However, this investigation did yield an important new observation, since approximately 10% of the injections caused pressor responses and increases in sympathetic discharge. The unexpected increases must have been caused by blockade of small groups of tonically active sympathoinhibitory neurons located throughout the RVLM. This disinhibition was not evoked from any specific region of the RVLM. In conclusion, the RVLM neurons and putative interneurons that tonically control the discharge of postganglionic renal and splenic neurons appear to be distributed homogeneously throughout this area. Neither excitatory nor inhibitory elements were organized topographically to specifically influence the renal or the splenic nerve. The neural organization responsible for the preferential effect on renal nerves may exist in the local microcircuitry within the RVLM and will be revealed only by an even more discrete analysis of these circuits.

Animals↗
PubMed1990

Pre- and postganglionic sympathetic activity in white rami of rats.

Multifiber sympathetic activity was recorded from the central end of severed 13th thoracic communicating rami in urethane-anesthetized rats before and after ganglionic blockade by chlorisondamine. Ganglionic blockade decreased nerve discharge by 49 +/- 10% (n = 7) indicating that these rami are composed of postganglionic axons (other than gray rami fibers) as well as preganglionic axons. Histological examination of excised T13 rami showed that postganglionic cell bodies are located along the course of these nerves.

Animals↗
PubMed1990

Selective control of sympathetic pathways to the kidney, spleen and intestine by the ventrolateral medulla in rats.

1. Electrical activity of multifibre renal, splenic, mesenteric and greater splanchnic nerves and 13th thoracic white rami was recorded in artificially respired, urethane-anaesthetized rats. Discharge of neurones in the rostral ventrolateral medulla was blocked by unilateral microinjections of the inhibitory amino acid glycine and effects on the electrical activity of these sympathetic nerves were compared. 2. Blockade of the rostral ventrolateral medulla caused greater decreases in discharge of renal than splenic nerves and had no consistent effect on mesenteric nerves. This blockade also decreased the discharge of the preganglionic white rami more than that of the preganglionic splanchnic nerves. 3. Postganglionic responses to rostral ventrolateral medulla blockade were always greater than preganglionic responses. 4. The arterial pressure and renal nerve responses to rostral ventrolateral medulla blockade in urethane-anaesthetized rats were not different from those in rats anaesthetized with alpha-chloralose. 5. These findings demonstrate that pre- and postganglionic sympathetic pathways to the kidney are more dependent upon excitatory drive from the rostral ventrolateral medulla than pathways directed to the spleen and intestine.

Animals↗
PubMed1989

Evaluation of cardiovascular control by neurons in the dorsal medulla of rats.

The contribution of sympathoexcitatory neurons in the dorsal medulla to the regulation of arterial pressure and the involvement of such neurons in integration of physiological responses or in the genesis of basal vasomotor tone are not well defined. In the present study discharge of neurons in the dorsal medulla of anesthetized rats was increased or decreased by microinjections of amino acids to examine effects on systemic arterial pressure, heart rate and blood flow and conductance of the renal and femoral vascular beds. Microinjections of excitatory D, L-homocysteic acid caused increases in arterial pressure of 18 +/- 2 mmHg, increases in heart rate ranging from 5-40 beats/min and renal vasoconstriction; the femoral bed constricted after some injections and dilated in response to others. Injections of the inhibitory amino acid glycine caused no consistent decreases in arterial pressure and heart rate and injections of the gamma-aminobutyric acid analog, muscimol were ineffective. These data demonstrate that neurons in the dorsal region of the rat medulla can contribute to regulation of arterial pressure and can integrate generalized differential changes in regional vascular resistance, but do not appear to be essential for the genesis of basal vasomotor tone.

Action Potentials↗
PubMed1989

Ventrolateral medullary neurones: effects on magnitude and rhythm of discharge of mesenteric and renal nerves in cats.

1. Discharge of whole mesenteric and renal nerves was recorded in eighteen chloralose-anaesthetized, artificially respired cats. 2. Inhibition of tonic activity of neurones within the rostral ventrolateral medulla (RVLM blockade) by bilateral application of glycine caused significant reductions in discharge of renal and mesenteric nerves, arterial blood pressure and heart rate. The decrease in discharge of renal nerves was significantly greater than that of mesenteric nerves. 3. During the response to glycine application, the spinal cord was transected at the first cervical segment. The magnitude of renal nerve discharge after transection was not different from that during blockade of the RVLM. On the other hand, mesenteric nerve activity increased following spinal cord transection, returning to control levels. 4. Power spectral analysis revealed that mesenteric and renal nerves discharged with periodicities ranging from 1 to 6 Hz. Application of glycine to the RVLM reduced the slow rhythm in firing of mesenteric and renal nerves similarly. Transection of the spinal cord resulted in further reduction in the rhythmicity in discharge of both nerves. 5. The results indicate that excitatory drive from the RVLM is crucial for the maintenance of on-going discharge of renal, but not of mesenteric nerves. However, such inputs are apparently essential to maintain the slow rhythm in firing of both nerves.

Action Potentials↗
PubMed1989

Cardiac and peripheral vascular contributions to hypotension in spinal cats.

On transection of the cervical spinal cord, substantial decreases in systemic arterial pressure and in discharge of many sympathetic nerves suggest the absence of sympathetic support to the cardiovascular system. However, discharge of mesenteric and splenic nerves is well maintained in spinal cats (R. L. Meckler and L. C. Weaver. J. Physiol. Lond. 396: 139-153, 1988; R. D. Stein and L. C. Weaver. J. Physiol. Lond. 396: 155-172, 1988). We proposed that the low arterial pressure in spinal animals was caused predominantly by decreased cardiac output and vasodilation in muscle and some visceral vascular beds but that sustained mesenteric and splenic discharge was causing significant splanchnic vasoconstriction and partial support of arterial pressure. Therefore, changes in cardiac output, total peripheral resistance, and resistance of constant-flow-perfused mesenteric visceral and hindlimb skeletal muscle vascular beds caused by interruption of cervical spinal pathways were assessed. Blockade of cervical pathways decreased arterial pressure as much by decreasing cardiac output as by decreasing total peripheral resistance. Resistances of the muscle and mesenteric vascular beds decreased equally. In conclusion, hypotension in spinal cats is caused by decreased cardiac output and by vasodilation, which is as prominent in mesenteric as it is in muscle vascular beds. The maintained mesenteric sympathetic discharge in spinal cats appears unable to produce significant support of vascular arterial resistance.

Animals↗
PubMed1989

Tonic influences from the rostral medulla affect sympathetic nerves differentially.

Tonically active neurons in the rostral ventrolateral medulla (RVLM) that project to the autonomic regions of the spinal cord are essential for maintenance of arterial blood pressure at normal levels. Microinjection of glycine into the RVLM in anesthetized cats to inhibit the tonic discharge of these neurons caused variable initial responses in renal and mesenteric nerve discharge and arterial blood pressure. These initial responses were consistently followed by more prolonged decreases in renal and mesenteric nerve discharge and decreases in arterial blood pressure. The tonic influences of neurons in the RVLM were found to be distributed unequally to sympathetic nerves because activity of renal nerves was decreased significantly more than that of mesenteric nerves. The variable nerve and cardiovascular responses during the first 1-3 min after glycine injection were not solely due to loading or unloading of baroreceptors because similar initial responses were seen in vagotomized and sinoaortic denervated cats. Additionally, when muscimol was microinjected into the same sites, only consistent and prolonged decreases in nerve discharge and blood pressure occurred. The inhibitory actions of muscimol on RVLM neurons caused significantly greater decreases in renal than mesenteric nerve activity. Together, these findings demonstrate that the tonic discharge of neurons in the RVLM has unequal influences on renal and mesenteric nerves.

Animals↗
PubMed1989

Effects of spinal cord transection on sympathetic discharge in decerebrate-unanesthetized cats.

Previous experiments in our laboratory have shown that discharge of splenic, mesenteric, and splanchnic nerves is well maintained after spinal cord transection in chloralose-anesthetized cats (8, 9, 11). The primary purpose of this investigation was to determine if maintained sympathetic discharge could be observed after spinal transection in the absence of chloralose anesthesia. In cats anesthetized with alphaxalone-alphadolone, changes in splanchnic discharge, blood pressure, and heart rate caused by decerebration and removal of the forebrain were observed. This procedure decreased blood pressure, increased heart rate, and had no immediate effect on sympathetic discharge or its rhythm (assessed by power density spectral analysis). One hour after decerebration and termination of anesthesia, splanchnic discharge had increased by approximately 36%. Next, effects of spinal cord transection on discharge of splanchnic, mesenteric, and renal nerves were observed in the decerebrate-unanesthetized cats. Splanchnic discharge decreased by 50%, mesenteric nerve discharge was unchanged, and renal nerve discharge decreased by 97%. Therefore, splanchnic nerve discharge was not as well maintained in decerebrate-unanesthetized cats as it had been in chloralose-anesthetized animals, and the remaining splanchnic discharge appeared to affect mesenteric nerves preferentially. Finally, spectral analysis of the splanchnic discharge demonstrated that before cord transection, most of the signal was in the 0- to 6-Hz frequency range, whereas after transection the proportion of signal in this frequency range was significantly reduced and the proportion in higher frequencies (7-25 Hz) was significantly increased. This loss of low-frequency rhythmicity is consistent with findings in our previous studies in chloralose-anesthetized cats.

Animals↗
PubMed1989

Characteristics of ongoing and reflex discharge of renal postganglionic neurons.

Characteristics of basal and reflex firing of single renal postganglionic fibers are reviewed to ascertain whether subpopulations of renal neurons can be distinguished. Moreover, characteristics of renal neurons are contrasted with those of sympathetic neurons innervating vascular and nonvascular tissues of the spleen and small intestine. Attempts to distinguish functional subtypes of renal neurons based on their responses to excitatory or inhibitory influences led to no clear conclusions. Responses of the renal population of neurons differed from those of the splenic and mesenteric populations of postganglionic neurons. Our findings provided no concrete answers about the neural mechanisms by which different functions of the kidney may be regulated selectively. This question continues to require careful and insightful investigation.

Action Potentials↗
PubMed1988

Persistent firing of splenic and renal nerves after acute decentralization but failure to produce ganglionic reflexes.

Experiments were done to evaluate the contribution of peripheral neural circuits to generation of ongoing splenic and renal sympathetic discharge as well as to the reflex alteration of this discharge by chemical stimulation of receptors of intestinal afferent nerves. After decentralization of the celiac and superior mesenteric ganglia, low amplitude spikes with low discharge rates still were observed in both nerves. Stimulation of intestinal receptors with bradykinin or capsaicin did not alter this residual firing. Cholinergic blockade eliminated most of this discharge. The source of the residual firing and its contribution to basal discharge of splenic and renal nerves remains to be determined.

Action Potentials↗
PubMed1988

Characteristics of ongoing and reflex discharge of single splenic and renal sympathetic postganglionic fibres in cats.

1. Electrical discharge of thirty-nine single splenic and renal postganglionic nerve fibres was recorded in artificially respired, chloralose-anaesthetized cats. 2. Ongoing discharge rates, averaged over 10 s periods, did not differ between renal and splenic fibres. All neurones of both groups had irregular discharge frequencies. 3. Half of the splenic population and all renal fibres had cardiac-related discharge patterns. Of those tested for respiratory-related firing, 30% of the splenic fibres and 69% of the renal fibres exhibited this pattern. 4. Firing of splenic fibres was less inhibited than that of renal fibres by stimulation of pressoreceptors with phenylephrine-induced increases in blood pressure. Firing of splenic fibres also was less excited than that of renal fibres by unloading pressoreceptors with depressor doses of sodium nitroprusside. 5. Chemical stimulation of splenic afferent nerves with bradykinin consistently elicited greater increases in splenic than renal nerve discharge by causing large increases in firing of all splenic fibres and smaller excitatory responses in 75% of the renal fibres. 6. Application of bradykinin to the intestinal serosa produced greater increases in renal than splenic nerve discharge by consistently causing increased firing of renal fibres and by causing excitation, inhibition, or no change in splenic fibre discharge. 7. Responses of splenic and renal fibres to stimulation of splenic and intestinal afferent nerves after spinal cord transection were similar to those responses elicited when the neuraxis was intact. 8. In conclusion, the differential reflex responses of splenic and renal neuronal populations can be due to the heterogeneity or to the intensity of responses within a neuronal population.

Action Potentials↗
PubMed1988

Multi- and single-fibre mesenteric and renal sympathetic responses to chemical stimulation of intestinal receptors in cats.

1. In cats anaesthetized with alpha-chloralose and artificially respired, stimulation of intestinal receptors with bradykinin caused greater reflex excitation of mesenteric than of renal efferent multifibre nerve activity and significant pressor responses. 2. Activity of all nerve bundles used in this study was inhibited by stimulation of pressoreceptors. Increases in systemic arterial pressure caused inhibition of activity of renal nerves which was significantly greater than that of mesenteric nerves. 3. Spinal transection caused significant decreases in tonic renal nerve activity without altering the ongoing discharge rate of mesenteric nerves. Stimulation of intestinal receptors in spinal cats still caused significant increases is discharge of mesenteric and renal nerves, indicating that this reflex contains a spinal component. 4. Recordings of activity of individual fibres within mesenteric (21) and renal (23) nerves provided information regarding the basis for the multifibre responses to stimulation of intestinal receptors. The same proportion of fibres from both nerves was excited, but the increase in activity of mesenteric fibres was significantly greater than that of renal fibres. 5. Mesenteric fibres could be classified into two groups, based on their sensitivity to pressoreceptor influences. Fibres that exhibited pressoreceptor-independent discharge had the greatest responses to stimulation of intestinal receptors. 6. Following spinal transection the majority of mesenteric fibres continued to fire, whereas most renal fibres became quiescent. 7. The non-uniform pattern of neuronal excitation to chemical stimulation of intestinal receptors was manifest after spinal transection, demonstrating that exclusively spinal pathways can mediate this differential response pattern. 8. These results support the hypothesis that viscero-sympathetic reflexes may be organized to cause preferential excitation of neural activity directed to the organ from which the reflex originates.

Action Potentials↗
PubMed1988

Blockade of spinal pathways decreases pre- and postganglionic discharge differentially.

Although discharge of many sympathetic nerves decreases substantially on transection of the spinal cord in cats, firing of splenic and mesenteric postganglionic nerves continues unabated (R. L. Meckler and L. C. Weaver, Brain Res. 338: 123-135, 1985; R. D. Stein and L. C. Weaver. J. Physiol. Lond. 396: 155-172, 1988). Therefore, ongoing sympathetic outflow directed to the splanchnic circulation was proposed to be less dependent on supraspinal excitatory drive than that directed to other vascular beds. Blockade or transection of cervical spinal pathways in chloralose-anesthetized cats significantly decreased firing of gastric, hepatic, adrenal, and lumbar chain sympathetic nerves. Discharge of gastric and hepatic nerves decreased as much as that of adrenal and lumbar chain nerves; therefore, sustained discharge in the absence of bulbospinal excitation is not a characteristic of all sympathetic nerves innervating the splanchnic circulation. In contrast, discharge of the preganglionic greater splanchnic nerves was not decreased after spinal transection, although it changed from a rhythmic to an asynchronous pattern. This provocative finding suggests that rhythmicity of preganglionic discharge may be important for effective synaptic transmission to some postganglionic neurons, since postganglionic gastric, hepatic, and adrenal nerve firing decreased in the presence of sustained but asynchronous preganglionic input.

Animals↗
PubMed1987

Neural, hemodynamic, and renal responses to stimulation of intestinal receptors.

Stimulation of visceral receptors with bradykinin has been shown to cause reflex increases in sympathetic nerve activity and systemic arterial pressure. In this investigation, serosal receptors of the intestine were stimulated by bradykinin in anesthetized cats to 1) compare mesenteric and renal sympathetic responses, 2) compare hemodynamic responses in mesenteric and renal beds, and 3) determine changes in renal function. This stimulation in intact animals caused pressor responses, significantly greater excitation of mesenteric than renal nerves, significantly greater mesenteric than renal vasoconstriction, diuresis, natriuresis, and, in denervated kidneys, increases in fractional sodium excretion. In vagotomized, sinoaortic-denervated cats, stimulation of intestinal receptors caused excitation of mesenteric nerve activity greater than renal for only 30 s. This sympathetic reflex response led to pressor responses, equal mesenteric and renal vasoconstriction, diuresis, natriuresis, and increased fractional excretion of sodium only in denervated kidneys. When abdominal perfusion pressure was held constant with an aortic snare in these same animals, the sympathetic reflexes initially caused greater mesenteric than renal vasoconstriction and antidiuresis and antinatriuresis only in innervated kidneys. These findings demonstrate that the intensity of hemodynamic and renal responses to stimulation of visceral receptors correlates well with the magnitude of sympathetic nerve responses.

Animals↗
PubMed1987

Pressoreceptor modulation of renal but not splenic sympathetic reflexes.

Influences of sinoaortic and vagally innervated vascular pressoreceptors on excitatory splenic and renal sympathetic responses to splenic receptor stimulation were investigated in anesthetized cats. These experiments demonstrated that these pressoreceptors have little apparent effect on the magnitude of splenic nerve responses to splenic receptor stimulation by capsaicin, bradykinin, or congestion. In contrast, activation of these pressoreceptors attenuated renal nerve responses to splenic receptor stimulation. Influences of sinoaortic and vagally innervated receptors on tonic sympathetic nerve activity also were evaluated. Stimulation of these receptors by small increases in arterial pressure (15-21 mmHg) caused equivalent inhibition of splenic and renal nerve activity; large increases (50-66 mmHg) caused significantly greater inhibition of renal than splenic nerve activity. These results illustrate that excitatory renal and splenic sympathetic responses to splenic receptor stimulation are not suppressed equally by pressoreceptor activation, vascular pressoreceptors can have greater inhibitory influences on tonic renal than splenic nerve activity, and vascular pressoreceptor influences on sympathetic reflexes are similar to those on tonic nerve activity.

Animals↗