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Interleukin-1 suppresses food intake via hypothalamic corticotropin-releasing factor
62 lnterleukin-I Suppresses Food Intake via Hypothalamic Corticotropin-Releasing Factor Akira Uehara, Toshikatsu Okumura, Yuichi Takasugi and Masayoshi Namiki
Renal Vascular Responses to Continuous and Burst-Type Renal Sympathetic Nerve Stimulation in Anesthetized Dogs Yoshikazu Matsuda, Takashi Fujila, Hart, mitsu U e m a t s u , Toshishige Shibamoto and Shozo Koyama
l)epartmcnt of Internal Medicine (liD, Asahikawa Medical Colh'ge, /lsahikawa 078, Japan
Department ~" Physiology, Division 2, Shinshu Unicersitv School ~f Medieine, Matstonoto 390, Japan
Although anorexia is a typical clinical manifestation frequently observed in patients with acute infectious diseases, the precise mechanism(s) by which anorexia develops in such pathophysiological conditions remains to be clarified, We have recently found that interleukin-I (lL-l), a cytokine produced by activated m o n o c y t e s / maerophages, stimulates the release of hypothalamic corticotropin-releasing factor. Since eorticotropin-releasing factor acts centrally in the brain to reduce food intake, we hypothesized that Ik-1 might induce anorexia through this central action of corticotropin-releasing factor. The present study was conducted on male Wistar rats to examine this hypothesis. On the basis of thee types of evidence, we now suggest thai IL-1 is closely involved in the development of anorexia during immunological stress such as is lk)und in acute infection. Firstly, it was observed that lipopolysaccharide, a potent stimulant of synthesis and release of endogenous IL-I, causes anorexia in a dose-related manner. Seeondly, intraperitoneal injection of IL-I resulted in a dose-related suppression of food intake. Thirdly, the anorexia induced by IL-1 was strongly diminished by immunological blocking of endogenous corticotropin-releasing factor in the brain. These results suggest that the central interaction between IL-I and corticotropin-releasing factor represents a mechanism by which the actiwltion of the immune system by such immunological challenges as occur in acute infectious diseases produces anorexia.
The physiological role of burst-type discharges of sympathetic nerves is unclear. We have, therefore, examined the renal vascular responses to continuous (10 Hz, 6 ll) V, I msec over 3 minutes) and burst-type (Ill Hz, 6 10 V, 1 msec over 1 sec at 1.4 sec intervals and for 1 see at 2.5 sec intervals over 3 minutes) renal sympathetic nerve stimulation in pentobarbital-anesthetizcd dogs. The left kidney was perfused at a constant flow rate and renal perfusion pressure was measured as an index of vascular resistance. The left renal sympathetic nerves were electrically stimulated by means of continuous and burst-type patterns of discharge. Continuous stimulation caused a rapid increase in renal perfusion pressure (113 + 28 mm Hg of control values at 0.6 min) followed by a decrease to 45 ± 14 mm ttg of eontrnl values 3 minutes after stimulation. However, both burst-types of stimulation produced a gradual increase in renal perfusion pressure (84 ± 26 turn Hg and 82 ± 27 m m Hg ovcr control values at I minute), which was maintained for 3 minutes. These data suggest that burst-type discharges of sympathetic nerves, which we actually observed in the electrical activity of renal nerves, play a major physiological rote in maintaining the peripheral vascular tonc.
lThe Autonomic Nervous System, 27: 485-489. 1991))
Three-Dimensional Architecture of the lnnervation of the Sphincter Pupillae Muscle in the Guinea-Pig Mariko Sasamoto
IThe Autonomic Nervous System. 27: 498-5113, 1990)
Role of Pancreatic Vagal and Sympathetic Afferents in the Reflex Increase of Renal Sympathetic Activity after Injection of Bile into the Canine Pancreatic Duct Itarumitsu U e m a t s u
Department o/" Physiolo,~:v, Dil'ision 2. Shinshu Unit'ersity School ~/ Medicine, Matsumoto 390, .lapan
We have investigated the structure of the peripheral autonomic nerves within and around the musculus sphincter pupiltae, by means of scanning electron microscopy. With this technique we were able to document the three-dimensional architecture of the network of nerves. Collagen fibrils, elastic fibres and basal laminae were removed by digestion with concentrated sodium hydroxide at 6(I°C. We found that Schwann cells issue several cytoplasmic processes that are attached to each other and form a framework supporting varicose and non-varicose nerve fibres. It was frequently observed that a Schwann cell cnsheath ten or more axons. Varicose fibres are occasionally scen without a Schwann cell sheath, running in the connective tissue between the smooth muscle cells. We conclude that the concept of " a u t o n o m i c ground plexus" originally proposed by Hillarp (1046, 1959) is an adequate account of the basic architecture of nerves in the iris. In the autonomic ground plexus nerve fibres run parallel down to the smallest nerve bundles, but they become independent in the very terminal portion.
This study was designed to investigate the effect of an injection of bile into the pancreatic duct on the mean blood pressure and the efferent renal nerve activity in anesthetized dogs. When autologous bile was injected into the pancreatic duct, there was a significant increase in blood pressure and in renal nerve activity. The maximum changes in animals with neuraxis intact were ÷ 26 ± 8 m m Hg and + 174 ± 13C~, respectively. Injection of physiolog ical saline into the pancreatic duct did not cause significant changes in either blood pressure or renal nerve activity. However, after subdiaphragmatic section of the vagus nerves or section ol the splanchnic nerves, the increases m blood pressure and renal nerve activity following injection of bile were markedly attenuated. In dogs with subdiaphragmatic vagotomy combined with both cocliac and superior mesenleric ganglionectomy, injection ot bile into the pancreatic duct caused only minimal changes in blood pressure and renal nerve activity from a baseline that was significantly lower than in the other groups. These resuhs suggest that injection of bile into the canine pancreatic duct evokes a reflex increase in blood pressure, which is mediated by activation of the sympathetic nervous system. The reflex is conducted by both the vagal and the sympathetic afferents originating in the pancreatic duct.
CFhc Autonomic Nervous System, 27: 4911-407, 1991))
(The Autonomic Nervous System, 27: 5i)4-511, l qt)t))
Department of Ophthalmology, Yamanashi Medical College, Yamanashi 409-38, Japan
Renal Vascular Responses to Continuous and Burst-Type Renal Sympathetic Nerve Stimulation in Anesthetized Dogs Yoshikazu Matsuda, Takashi Fujila, Hart, mitsu U e m a t s u , Toshishige Shibamoto and Shozo Koyama
l)epartmcnt of Internal Medicine (liD, Asahikawa Medical Colh'ge, /lsahikawa 078, Japan
Department ~" Physiology, Division 2, Shinshu Unicersitv School ~f Medieine, Matstonoto 390, Japan
Although anorexia is a typical clinical manifestation frequently observed in patients with acute infectious diseases, the precise mechanism(s) by which anorexia develops in such pathophysiological conditions remains to be clarified, We have recently found that interleukin-I (lL-l), a cytokine produced by activated m o n o c y t e s / maerophages, stimulates the release of hypothalamic corticotropin-releasing factor. Since eorticotropin-releasing factor acts centrally in the brain to reduce food intake, we hypothesized that Ik-1 might induce anorexia through this central action of corticotropin-releasing factor. The present study was conducted on male Wistar rats to examine this hypothesis. On the basis of thee types of evidence, we now suggest thai IL-1 is closely involved in the development of anorexia during immunological stress such as is lk)und in acute infection. Firstly, it was observed that lipopolysaccharide, a potent stimulant of synthesis and release of endogenous IL-I, causes anorexia in a dose-related manner. Seeondly, intraperitoneal injection of IL-I resulted in a dose-related suppression of food intake. Thirdly, the anorexia induced by IL-1 was strongly diminished by immunological blocking of endogenous corticotropin-releasing factor in the brain. These results suggest that the central interaction between IL-I and corticotropin-releasing factor represents a mechanism by which the actiwltion of the immune system by such immunological challenges as occur in acute infectious diseases produces anorexia.
The physiological role of burst-type discharges of sympathetic nerves is unclear. We have, therefore, examined the renal vascular responses to continuous (10 Hz, 6 ll) V, I msec over 3 minutes) and burst-type (Ill Hz, 6 10 V, 1 msec over 1 sec at 1.4 sec intervals and for 1 see at 2.5 sec intervals over 3 minutes) renal sympathetic nerve stimulation in pentobarbital-anesthetizcd dogs. The left kidney was perfused at a constant flow rate and renal perfusion pressure was measured as an index of vascular resistance. The left renal sympathetic nerves were electrically stimulated by means of continuous and burst-type patterns of discharge. Continuous stimulation caused a rapid increase in renal perfusion pressure (113 + 28 mm Hg of control values at 0.6 min) followed by a decrease to 45 ± 14 mm ttg of eontrnl values 3 minutes after stimulation. However, both burst-types of stimulation produced a gradual increase in renal perfusion pressure (84 ± 26 turn Hg and 82 ± 27 m m Hg ovcr control values at I minute), which was maintained for 3 minutes. These data suggest that burst-type discharges of sympathetic nerves, which we actually observed in the electrical activity of renal nerves, play a major physiological rote in maintaining the peripheral vascular tonc.
lThe Autonomic Nervous System, 27: 485-489. 1991))
Three-Dimensional Architecture of the lnnervation of the Sphincter Pupillae Muscle in the Guinea-Pig Mariko Sasamoto
IThe Autonomic Nervous System. 27: 498-5113, 1990)
Role of Pancreatic Vagal and Sympathetic Afferents in the Reflex Increase of Renal Sympathetic Activity after Injection of Bile into the Canine Pancreatic Duct Itarumitsu U e m a t s u
Department o/" Physiolo,~:v, Dil'ision 2. Shinshu Unit'ersity School ~/ Medicine, Matsumoto 390, .lapan
We have investigated the structure of the peripheral autonomic nerves within and around the musculus sphincter pupiltae, by means of scanning electron microscopy. With this technique we were able to document the three-dimensional architecture of the network of nerves. Collagen fibrils, elastic fibres and basal laminae were removed by digestion with concentrated sodium hydroxide at 6(I°C. We found that Schwann cells issue several cytoplasmic processes that are attached to each other and form a framework supporting varicose and non-varicose nerve fibres. It was frequently observed that a Schwann cell cnsheath ten or more axons. Varicose fibres are occasionally scen without a Schwann cell sheath, running in the connective tissue between the smooth muscle cells. We conclude that the concept of " a u t o n o m i c ground plexus" originally proposed by Hillarp (1046, 1959) is an adequate account of the basic architecture of nerves in the iris. In the autonomic ground plexus nerve fibres run parallel down to the smallest nerve bundles, but they become independent in the very terminal portion.
This study was designed to investigate the effect of an injection of bile into the pancreatic duct on the mean blood pressure and the efferent renal nerve activity in anesthetized dogs. When autologous bile was injected into the pancreatic duct, there was a significant increase in blood pressure and in renal nerve activity. The maximum changes in animals with neuraxis intact were ÷ 26 ± 8 m m Hg and + 174 ± 13C~, respectively. Injection of physiolog ical saline into the pancreatic duct did not cause significant changes in either blood pressure or renal nerve activity. However, after subdiaphragmatic section of the vagus nerves or section ol the splanchnic nerves, the increases m blood pressure and renal nerve activity following injection of bile were markedly attenuated. In dogs with subdiaphragmatic vagotomy combined with both cocliac and superior mesenleric ganglionectomy, injection ot bile into the pancreatic duct caused only minimal changes in blood pressure and renal nerve activity from a baseline that was significantly lower than in the other groups. These resuhs suggest that injection of bile into the canine pancreatic duct evokes a reflex increase in blood pressure, which is mediated by activation of the sympathetic nervous system. The reflex is conducted by both the vagal and the sympathetic afferents originating in the pancreatic duct.
CFhc Autonomic Nervous System, 27: 4911-407, 1991))
(The Autonomic Nervous System, 27: 5i)4-511, l qt)t))
Department of Ophthalmology, Yamanashi Medical College, Yamanashi 409-38, Japan