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K N Westlund

Publications and source records attributed to K N Westlund.

At least 19 recordsLinked to original sources
PubMed1997

Neuroanatomy of the pain system and of the pathways that modulate pain.

We review many of the recent findings concerning mechanisms and pathways for pain and its modulation, emphasizing sensitization and the modulation of nociceptors and of dorsal horn nociceptive neurons. We describe the organization of several ascending nociceptive pathways, including the spinothalamic, spinomesencephalic, spinoreticular, spinolimbic, spinocervical, and postsynaptic dorsal column pathways in some detail and discuss nociceptive processing in the thalamus and cerebral cortex. Structures involved in the descending analgesia systems, including the periaqueductal gray, locus ceruleus, and parabrachial area, nucleus raphe magnus, reticular formation, anterior pretectal nucleus, thalamus and cerebral cortex, and several components of the limbic system are described and the pathways and neurotransmitters utilized are mentioned. Finally, we speculate on possible fruitful lines of research that might lead to improvements in therapy for pain.

Animals↗
PubMed1997

Surgical interruption of a midline dorsal column visceral pain pathway. Case report and review of the literature.

A punctate midline myelotomy performed in a patient effectively eliminated residual, intractable pelvic pain, which remained after resolution of uterine cervical cancer. The authors describe the case history of the patient, in whom pain assessments were made, and a surgical procedure performed. Despite large doses of opiate analgesic medications, the patient experienced constant pressure pain in the right lower pelvis, with excruciating pain on bowel movement. Severe weight loss necessitated better pain control. A minimally invasive surgical procedure, a 5-mm deep puncture using a 16-gauge needle on either side of the median septum in the dorsal column of the spinal cord (T-8), resulted in no new neurological deficits. Narcotic medication was tapered, no pain was reported, and the patient resumed daily household activity. Midline myelotomy has typically been performed with the intention of eliminating the crossing fibers of the spinothalamic tract in the anterior white matter commissure. The punctate midline myelotomy described here was performed with the specific intention of interrupting a newly described visceral pain pathway that ascends to higher brain centers through the midline of the dorsal column. The effectiveness of the pain relief seen in this patient suggests that visceral pain of the pelvis in humans may be transmitted in the midline of the dorsal column, as has been recently reported in studies using rats. The effectiveness of the punctate midline myelotomy performed in this one case of pelvic visceral pain suggests that the surgery may eventually be effective in greatly reducing or replacing opiate narcotic medication for visceral pain management.

Activities of Daily Living↗
PubMed1996

Ultrastructural localization of glutamate receptor subunits (NMDAR1, AMPA GluR1 and GluR2/3) and spinothalamic tract cells.

The associations of glutamate receptor subunits (NMDAR1, AMPA GluR1 and GluR2/3) and spinothalamic tract neurons in the rat lumbar spinal cord dorsal horn were investigated. Staining for NMDAR1 and AMPA GluR1 and GluR2/3 receptor subunits was observed throughout the spinothalamic tract soma and dendrites, particularly in association with the rough endoplasmic reticulum and some postsynaptic membrane sites. Immunostaining for NMDAR1 and AMPA GluR2/3 was also noted in presynaptic membrane sites. Localization of both NMDA and AMPA glutamate receptor subunits in association with spinothalamic tract neurons provides anatomical evidence in support of the various interactions reported for glutamate receptors in nociception. Presynaptic localization of the AMPA GluR2/3 receptor subunit suggests that spinothalamic tract cells may also be affected presynaptically by AMPA glutamate receptor interactions.

Animals↗
PubMed1996

Potentiation of thalamic responses to colorectal distension by visceral inflammation.

Responses of single viscerosensitive units in the ventral posterolateral (VPL) nucleus of the thalamus to cutaneous stimuli and graded colorectal distension (CRD) were recorded before and after colon inflammation by mustard oil (MO). The spontaneous firing rate increased around 25 min after the injection of MO. Responses to CRD obtained after this time increased significantly. In contrast, responses to cutaneous stimuli were attenuated and no substantial variations in the size of the cutaneous receptive fields were observed. A lesion of the dorsal column (DC) at T10 dramatically decreased the background activity and almost totally abolished the responses to CRD and to innocuous cutaneous stimuli but did not significantly affect the responses to noxious cutaneous pinch. These results indicate that colon inflammation potentiates thalamic responses to visceral stimuli while decreasing those to cutaneous stimuli.

Animals↗
PubMed1996

An I2 imidazoline ligand, RS 45041, potentiates hyperalgesia in acute arthritis.

Descending inhibition is increased after the induction of inflammation of the knee. The present study investigated whether this effect is mediated through alpha 2-adrenoceptors and/or I2 imidazoline receptors in the rat. An alpha 2-adrenoceptor antagonist, RX 821002, a selective I2 imidazoline ligand, RS 45041, and idazoxan, which has affinity for both these receptor types, were administered. After the induction of acute arthritis by intra-articular injection of kaolin and carrageenan, the agents binding to I2 imidazoline receptors further reduced the paw withdrawal latency to radiant heat beyond that induced by acute arthritis, i.e. these drugs were pronociceptive, potentiating hyperalgesia. These results suggest that I2 imidazoline receptors have an important role to play in modulation of hyperalgesia during acute inflammation. Development of I2 imidazoline drugs may prove useful in the treatment of hyperalgesia.

Acute Disease↗
PubMed1996

Association of spinal lamina I projections with brainstem catecholamine neurons in the monkey.

In addition to giving primary projections to the parabrachial and periaqueductal gray regions, ascending lamina I projections course through and terminate in brainstem regions known to contain catecholaminergic cells. For this reason, double-labeling experiments were designed for analysis with light and electron microscopy. The lamina I projections in the Cynomolgus monkey were anterogradely labeled with Phaseolus vulgaris leucoagglutinin (PHA-L) and catecholamine-containing neurons were labeled immunocytochemically for tyrosine hydroxylase (TH). Light level double-labeling experiments revealed that the terminations of the lamina I ascending projections through the medulla and pons strongly overlap with the localization of catecholamine cells in: the entire rostrocaudal extent of the ventrolateral medulla (A1 caudally, C1 rostrally); the solitary nucleus and the dorsomedial medullary reticular formation (A2 caudally, C2 rostrally); the ventrolateral pons (A5); the locus coeruleus (A6); and the subcoerulear region, the Kölliker-Fuse nucleus, and the medial and lateral parabrachial nuclei (A7). At the light microscopic level, close appositions between PHA-L-labeled lamina I terminal varicosities and TH-positive dendrites and somata were observed, particularly in the A1, A5 and the A7 cell groups on the contralateral side. At the electron microscopic level, examples of lamina I terminals were found synapsing on cells of the ventrolateral catecholamine cell groups in preliminary studies. The afferent input relayed by these lamina I projections could provide information about pain, temperature, and metabolic state as described previously. Lamina I input could impact interactions of the catecholamine system with higher brain centers modulating complex autonomic, endocrine, sensory, motor, limbic and cortical functions such as memory and learning. Nociceptive lamina I input to catecholamine cell regions with projections back to the spinal cord could form a feedback loop for control of spinal sensory, autonomic and motor activity.

Animals↗
PubMed1996

Is there a pathway in the posterior funiculus that signals visceral pain?

The present report provides evidence that axons in the medial part of the posterior column at T10 convey ascending nociceptive signals from pelvic visceral organs. This evidence was obtained from human surgical case studies and histological verification of the lesion in one of these cases, along with neuroanatomical and neurophysiological findings in animal experiments. A restricted lesion in this area can virtually eliminate pelvic pain due to cancer. The results remain excellent even in cases in which somatic structures of the pelvic body wall are involved. Following this procedure, neurological testing reveals no additional neurological deficit. There is no analgesia to pinprick stimuli applied to the body surface, despite the relief of the visceral pain. Since it is reasonable to attribute the favorable results of limited midline myelotomies to the interruption of axons of visceral nociceptive projection neurons in the posterior column, we have performed experiments in rats to test this hypothesis. The results in rats indicate that the dorsal column does indeed include a nociceptive component that signals pelvic visceral pain. The pathway includes neurons of the postsynaptic dorsal column pathway at the L6-S1 segmental level, axons of these neurons in the fasciculus gracilis, and neurons of the nucleus gracilis and the ventral posterolateral nucleus of the thalamus.

Adult↗
PubMed1996

Visceral nociceptive input into the ventral posterolateral nucleus of the thalamus: a new function for the dorsal column pathway.

1. Extracellular recordings were made from single neurons in the ventral posterolateral (VPL) nucleus of the thalamus in anesthetized male rats. VPL cells that responded to colorectal distension (CRD) were further tested with cutaneous and visceral stimuli before and after sequential lesions of the dorsal column (DC) and of the ventrolateral column (VLC). 2. A total of 105 VPL viscerosensitive cells was isolated. In this study, we report results from 27 cells that were tested for visceral responses before and after lesions of the DC and the VLC. 3. Ten VPL cells, isolated in 10 different rats, that responded to CRD and to activation of their cutaneous receptive fields with innocuous and noxious stimuli were tested before and after a lesion of the DC and again after a lesion of the VLC. Ten other VPL cells were isolated in 10 different rats. These were also tested for responses to CRD and to cutaneous stimuli spanning the innocuous and the noxious range before and after a lesion of the VLC and again after a lesion of the DC. 4. A lesion of the DC dramatically reduced the responses of VPL cells to CRD as well as to innocuous cutaneous stimuli. A lesion of the VLC reduced and sometimes abolished the responses of VPL cells to noxious cutaneous stimuli; however, its effect on the responses to visceral or innocuous cutaneous stimuli was minor when compared with that of a DC lesion. 5. The activity of seven VPL cells that responded to CRD and to cutaneous stimuli was observed after an injection of a chemical irritant, mustard oil (MO), into the colon. These cells showed an increase in background activity that started approximately 25-30 min after the MO injection. A lesion of the DC reduced the background activity of the cells to levels near initial values. 6. We conclude that the DC in the rat contains a pathway that is more important for transmitting visceral nociceptive signals to the VPL nucleus than are pathways in the VLC, including the spinothalamic tract. Conversely, the VLC is more important for transmitting nociceptive information of cutaneous origin.

Animals↗
PubMed1996

Pelvic visceral input into the nucleus gracilis is largely mediated by the postsynaptic dorsal column pathway.

1. The purpose of this study was to investigate a proposed role for the postsynaptic dorsal column (PSDC) pathway in mediating visceral nociceptive input into the dorsal column (DC) nuclei. 2. In one group of animals, the hypogastric nerves were sectioned, thereby restricting colorectal input into the cord to pelvic afferent pathways known to coverage on lower lumbar and sacral segments. Extracellular recording were made from 41 nucleus gracilis (NG) cells that responded to colorectal distension (CRD). Results reported are from 15 NG cells that were tested before and after the administration of morphine into the sacral cord by microdialysis. 3. The responses of 11 NG cells to CRD were dramatically reduced by morphine infused into the sacral cord through a microdialysis fiber. This reduction was reversed by an intravenous injection of naloxone. Microdialysis administration of 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) or a lesion of the DC also abolished the responses of the NG cells to CRD. 4. Four NG cells that responded to CRD showed an increase in their background activity approximately 25 min after an injection of mustard oil (MO). This increase in activity was counteracted by morphine or by a lesion of the DC. 5. In a second group of animals, recordings were made from 28 PSDC cells in the L0-S1 segments of the cord. These units were antidromically activated by stimulation of the upper cervical fasciculus gracilis. The projections of five PSDC neurons into the NG were traced with the use of antidromic mapping. Results are reported for the responses of 12 PSDC cells to CRD and to cutaneous stimuli before and after morphine administration into the sacral cord by microdialysis. 6. Morphine given spinally reduced the responses of 12 PSDC cells to CRD. This reduction was reversed by an intravenous injection of naloxone. CNQX administered spinally also abolished the responses to CRD of the PSDC cells tested. 7. Four other PSDC cells were studied before and after an injection of MO into the colon. Their background activity started to increase within 25 min after the injection. Morphine suppressed this increase in background activity and this effect of morphine was reversed by naloxone. 8. The responses of NG cells to cutaneous stimuli were not significantly affected by morphine in the dose used. On the other hand, morphine significantly reduced the responses of PSDC cells to noxious cutaneous stimuli although this effect was not as dramatic as that on responses to visceral stimuli. 9. From the results of the studies described in this and the companion paper, we conclude that there is an important pelvic visceral nociceptive pathway involving PSDC neurons that synapse in the NG. The NG in turn activates neurons in the ventral posterolateral (VPL) nucleus of the thalamus. We presume that activation of VPL neurons by noxious visceral stimulation contributes to visceral pain sensation and thus that pelvic visceral pain depends largely on activity in the DC-medial lemniscus system.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1996

Dorsal root reflexes in articular afferents occur bilaterally in a chronic model of arthritis in rats.

1. Chronic arthritis was produced in rats by the injection of incomplete Freund's adjuvant into one knee joint. By 3-5 days later the rats had developed unilateral swelling of the injected knee and demonstrated bilateral hyperalgesia to radiant heat stimuli applied to the foot. 2. In the same rats anesthetized 3-5 days after the injection, dorsal root reflexes could be recorded bilaterally from the proximal ends of the cut medial articular nerves (MANs) of the knee joint. 3. The dorsal root reflexes consisted of large, medium-sized, and small action potentials evoked in response to phasic mechanical stimulation of the lateral aspect of the knee. The activity was greater in the MAN ipsilateral to the injection than in the contralateral MAN. 4. Local application of capsaicin on the side ipsilateral or contralateral to the arthritis dramatically reduced the dorsal root reflexes recorded from the contralateral MAN, indicating that these dorsal root reflexes depended on activity in fine afferent fibers containing capsaicin receptors, presumably C fibers. Local application of capsaicin on either side did not significantly change the dorsal root reflexes recorded from the ipsilateral MAN. These dorsal root reflexes were presumably conducted in afferent fibers that lacked capsaicin receptors, including A beta- and A delta-fibers.

Action Potentials↗
PubMed1995

Dexamethasone and activators of the protein kinase A and C signal transduction pathways regulate neuronal calcitonin gene-related peptide expression and release.

Primary cultures of adult rat dorsal root ganglia (DRG) neurons were used to determine if activation of either the protein kinase A or C signal transduction pathways or treatment with the synthetic glucocorticoid dexamethasone modulate neuronal calcitonin gene-related peptide (CGRP) synthesis and release. DRG are the sites of neuronal cell bodies known to produce abundant CGRP levels, and to send axons peripherally to blood vessels and centrally to the spinal cord. Using immunocytochemical techniques, we confirmed that synthesis of immunoreactive CGRP (iCGRP) is restricted to a subpopulation of DRG neurons. Subsequently, we determined that treatment (24 h) of the neurons with either dibutyryl cAMP (1 mM) or phorbol 12-myristate 13-acetate (2 microM) increased CGRP mRNA content 2.2 +/- 0.4 (n = 6, p < 0.03) and 3.0 +/- 0.6-fold (n = 6, P < 0.02) respectively, while secreted iCGRP levels were increased 1.8 +/- 0.2 (n = 14, P < 0.005) and 4.5 +/- 1.0 (n = 14, P < 0.001)-fold over control levels. Treatment of the neurons with dexamethasone alone had no effect on CGRP expression; however, this agent was able to significantly attenuate the stimulatory effects of NGF on both CGRP mRNA accumulation and release of iCGRP. Time course studies demonstrated that in the phorbol ester treated neurons CGRP mRNA levels continued to increase at 48 h, while maximal induction with dibutyryl cAMP occurred at approximately 12 h. These results indicate that local and/or circulating factors which act through the protein kinase A and C signal transduction pathways upregulate both CGRP expression and release, while glucocorticoids attenuate the stimulatory effects of NGF.

Animals↗
PubMed1995

NGF-producing transfected 3T3 cells: behavioral and histological assessment of transplants in nigral lesioned rats.

The rodent fibroblast clonal cell line, 3T3, was retrovirally transfected with the rat nerve growth factor (NGF) gene and selected for NGF synthesis. This study tested the hypothesis that transplanted 3T3 cells, transfected to secrete nerve growth factor (3T3NGF+), change motor behavioral indices created by striatal denervation in a dose-dependent fashion. 3T3NGF+ cells were transplanted into the lateral ventricle of rats following ipsilateral lesions of the substantia nigra pars compacta by stereotaxic injections of 6-hydroxydopamine (10 micrograms), an established lesion model. Control groups included vehicle injections and transplanted untransfected cells. The extent of the lesions was measured by determining rotational behavior before and two weeks after transplantation. Immediately prior to transplantation, cells were incubated with the fluorescent dye marker, Dil. To assess cell viability, whole brains were cryosectioned and examined for Dil-labeled 3T3 cells using fluorescent microscopy. The number of Dil-labeled profiles in five animals per group were counted in at least five noncontiguous sections per animal. From these data a statistically derived estimate of viable, transplanted 3T3 cells was obtained. The number of surviving transplanted cells correlated with the behavioral changes measured. The 3T3NGF+ transplants reduced rotational behavior, while control 3T3 transplants exacerbated rotational behavior. Thus, while NGF delivery was found to be beneficial, it was apparent that naive 3T3 had detrimental effects. These results underscore the importance of making dose-response measurements when attempting transplant-based modifications of CNS behavior.

3T3 Cells↗
PubMed1995

The role of glutamate and GABA receptors in the generation of dorsal root reflexes by acute arthritis in the anaesthetized rat.

1. In rats anaesthetized with pentobarbitone sodium, a unilateral acute arthritis was produced by the injection of kaolin and carrageenan into one knee-joint cavity. Four hours after injection, the medial articular nerve (MAN) was sectioned distally and recordings obtained from the proximal stump of the nerve. 2. Centrifugally conducted action potentials were recorded from the cut MAN following the development of arthritis. Acute dorsal rhizotomy, but not sympathectomy, prevented the action potentials, and so it is concluded that the action potentials represent dorsal root reflexes. 3. Central administration of either the GABAA receptor antagonist, bicuculline, or the non-NMDA receptor antagonist, CNQX, also prevented dorsal root reflexes in the MAN. 4. Neither the GABAB receptor antagonist, CGP35348, nor the NMDA receptor antagonist, AP7, altered the dorsal root reflexes in the MAN. 5. It is concluded that arthritis causes excess primary afferent depolarization in the dorsal horn of the spinal cord leading to dorsal root reflexes. It is proposed that these dorsal root reflexes contribute to the inflammation.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1995

The efferent projections of the periaqueductal gray in the rat: a Phaseolus vulgaris-leucoagglutinin study. I. Ascending projections.

This study has examined the ascending projections of the periaqueductal gray in the rat. Injections of Phaseolus vulgaris-leucoagglutinin were placed in the dorsolateral or ventrolateral subregions, at rostral or caudal sites. From either region, fibers ascended via two bundles. The periventricular bundle ascended in the periaqueductal and periventricular gray matter. At the posterior commissure level, this bundle divided into a dorsal component that terminated in the intralaminar and midline thalamic nuclei, and a ventral component that supplied the hypothalamus. The ventral bundle formed in the deep mesencephalic reticular formation and supplied the ventral tegmental area, substantia nigra pars compacta, and the retrorubral field. The remaining fibers were incorporated into the medial forebrain bundle. These supplied the lateral hypothalamus and forebrain structures, including the preoptic area, the nuclei of the diagonal band, and the lateral division of the bed nucleus of the stria terminalis. The dorsolateral subregion preferentially innervated the centrolateral and paraventricular thalamic nuclei and the anterior hypothalamic area. The ventrolateral subregion preferentially innervated the parafascicular and central medial thalamic nuclei, the lateral hypothalamic area, and the lateral division of the bed nucleus of the stria terminalis. Although the dorsolateral and ventrolateral subregions gave rise to differential projections, the projections from both the rostral and caudal parts of either subregion were similar. This suggests that the dorsolateral and ventrolateral subregions are organized into longitudinal columns that extend throughout the length of the periaqueductal gray. These columns may correspond to those demonstrated in recent physiological studies.

Animals↗
PubMed1995

The efferent projections of the periaqueductal gray in the rat: a Phaseolus vulgaris-leucoagglutinin study. II. Descending projections.

The descending projections of the periaqueductal gray (PAG) have been studied in the rat using the anterograde tracer Phaseolus vulgaris-leucoagglutinin. The tracer was injected into the dorsolateral or ventrolateral subdivisions of the PAG at rostral or caudal sites. It was found that the patterns of the descending projections of the rostral and caudal parts of the dorsolateral PAG were the same and that the patterns of the descending projections of the rostral and caudal parts of the ventrolateral PAG were the same. However, the patterns of projections of the dorsolateral and ventrolateral PAG subregions were substantially different. These results suggest that the dorsolateral and ventrolateral parts of the PAG are organized into longitudinal columns that extend throughout the length of the PAG. The axons of PAG neurons descended through the pons and medulla via two routes. A small fiber bundle was present in the periaqueductal gray and in the periventricular area. This bundle distributed fibers and terminals locally within the periaqueductal gray and in the locus coeruleus and Barrington's nucleus. A larger bundle had a diffuse arrangement in the pontine reticular formation, however, and it had a more restricted distribution in the medulla, where it occupied a position dorsolateral to the pyramid. This bundle supplied structures in the pontine and medullary tegmentum. The dorsolateral column preferentially supplied the locus coeruleus, subcoeruleus, the gigantocellular nucleus pars alpha, the rostral part of the paragigantocellular nucleus, and the region of the A5 noradrenergic cell group. The ventrolateral column preferentially supplied the nucleus raphe magnus, the caudal part of the lateral paragigantocellular nucleus, and the rostroventrolateral reticular nucleus.

Animals↗
PubMed1995

Fiber types contributing to dorsal root reflexes induced by joint inflammation in cats and monkeys.

1. Injection of kaolin and carrageenan into the knee joint of cats or monkeys resulted in an acute inflammation. Four hours after injection of the knee joint, efferent activity could be evoked in articular afferent fibers and in dorsal root filaments. We interpret this efferent activity to be dorsal root reflexes (DRRs). Under our experimental conditions, the DRRs were generally synchronized compound action potentials, although in some cases single-unit activity was also observed. 2. DRRs were not produced in animals with uninflamed knee joints and normal body temperatures. 3. Recordings from two different sites on cut dorsal root filaments ipsilateral to the inflamed knee joint allowed the determination of the conduction velocities of groups of afferent fibers carrying DRRs. The DRRs occurred in A beta-, A delta-, and C fibers. However, in these experiments the peripheral destination of the afferent fibers was unknown. 4. To prove that DRRs occurred in joint afferents, recordings were made from two different sites on the proximal stump of the medial articular nerve that innervated the inflamed knee. The DRRs were again found in all fiber types, i.e., group II, III, and IV (A beta, A delta, and C) articular afferent fibers. 5. Compound DRRs were recorded from the central end of a cut dorsal root filament after electrical stimulation at C fiber intensity of a dorsal root adjacent to the filament. This DRR activity was eliminated by extensive dorsal rhizotomies of the L2-S1 roots.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1995

Enhanced neuronal expression of calcitonin gene-related peptide in mineralocorticoid-salt hypertension.

Dorsal root ganglia neuronal cell bodies synthesize the vasodilator neuropeptide calcitonin gene-related peptide and innervate the blood vessels and spinal cord sites (laminae I and II) involved in blood pressure regulation. We previously demonstrated that calcitonin gene-related peptide mRNA content is significantly decreased in dorsal root ganglia and that immunoreactive calcitonin gene-related peptide levels are reduced in laminae I and II of the dorsal horn of the spinal cord in the spontaneously hypertensive rat compared with Wistar-Kyoto control rats. To determine whether neuronal calcitonin gene-related peptide expression is also altered in mineralocorticoid-salt hypertension, we quantified calcitonin gene-related peptide mRNA levels in dorsal root ganglia and protein content in laminae I and II of the spinal cord in rats with mineralocorticoid-salt-induced hypertension. To control for pellet implantation, saline drinking water, and/or uninephrectomy, four normotensive groups were similarly studied. By Northern hybridization analysis, the ratio of calcitonin gene-related peptide mRNA to 18S rRNA was increased approximately fivefold in hypertensive rats (33 +/- 7) compared with each of the four normotensive control groups (average of the four groups, 6 +/- 0.5; P < .01, mineralocorticoid-salt group versus each group). The density of the peptide, quantified by computer-assisted image analysis, in laminae I and II in the hypertensive rats was also increased (66 +/- 1 versus average of the four groups, 46 +/- 2 arbitrary units; P < .001, mineralocorticoid-salt group versus each group). In conclusion, neuronal levels of calcitonin gene-related peptide mRNA and protein are increased in mineralocorticoid-salt hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗