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Biomedical subjects

H Kannan

Publications and source records attributed to H Kannan.

At least 19 recordsLinked to original sources
PubMed2001

Nociceptin/orphanin FQ and [Phe(1)psi(CH2-NH)Gly2]nociceptin(1-13)NH2 modulates the activity of hypothalamic paraventricular nucleus neurons in vitro.

Nociceptin, also known as orphanin FQ (N/OFQ), an endogenous ligand for the orphan opioid receptor-like(1) (ORL(1)) receptor, is moderately expressed in the hypothalamic paraventricular nucleus (PVN) involved in the integrative control of the function of the endocrine and autonomic nervous systems. Our previous study demonstrated that intracerebroventricular administration of N/OFQ elicits an inhibitory action on the function of the cardiovascular and sympathetic nervous systems in conscious rats. However, the effects of N/OFQ on PVN neurons have not been examined. We investigated the effects of N/OFQ on PVN neurons using a whole-cell patch-clamp recording technique in rat brain slices. N/OFQ (30-1000 nM) hyperpolarized membrane potentials in type 1 and type 2 neurons of the PVN classified by the electrophysiological property. [Phe(1)psi(CH2-NH)Gly2]nociceptin(1-13)NH2 (Phepsi) (1-9 microM), a presumed competitive antagonist of the ORL(1) receptor, also hyperpolarized membrane potential in both types of neurons. In voltage clamp studies, N/OFQ (3-3000 nM) activated a K+ current concentration-dependently in 69.7% of PVN neurons with an EC(50) of 72.4+/-12 nM. Phepsi (100-9000 nM) also activated a K+ current with an EC(50) of 818+/-162 nM in PVN neurons, and significantly reduced the amplitude of the N/OFQ-stimulated current. The N/OFQ-induced current was not antagonized by the classical opioid receptor antagonist naloxone and putative antagonist nocistatin. These findings suggest that N/OFQ may have a functional role in the PVN.

Animals↗
PubMed2001

Orexin depolarizes rat hypothalamic paraventricular nucleus neurons.

Orexins, also called hypocretins, are newly discovered hypothalamic peptides that are thought to be involved in various physiological functions. In spite of the fact that orexin receptors, especially orexin receptor 2, are abundant in the hypothalamic paraventricular nucleus (PVN), the effects of orexins on PVN neurons remain unknown. Using a whole cell patch-clamp recording technique, we investigated the effects of orexin-B on PVN neurons of rat brain slices. Bath application of orexin-B (0.01-1.0 microM) depolarized 80.8% of type 1 (n = 26) and 79.2% of type 2 neurons tested (n = 24) in the PVN in a concentration-dependent manner. The effects of orexin-B persisted in the presence of TTX (1 microM), indicating that these depolarizing effects were generated postsynaptically. Addition of Cd(2+) (1 mM) to artificial cerebrospinal fluid containing TTX (1 microM) significantly reduced the depolarizing effect in type 2 neurons. These results suggest that orexin-B has excitatory effects on the PVN neurons mediated via a depolarization of the membrane potential.

Animals↗
PubMed2001

Cardiovascular changes induced by central hypertonic saline are accompanied by glutamate release in awake rats.

To elucidate neurochemical mechanisms responsible for cardiovascular responses induced by central salt loading, we directly perfused the paraventricular nucleus (PVN) of the hypothalamus region with hypertonic saline (0.3 or 0.45 M) by using an in vivo brain microdialysis technique. We then measured the extracellular concentrations of glutamate in the PVN region in conscious rats along with the blood pressure and heart rate. Blood pressure, heart rate, and glutamate levels were increased by perfusion of 0.45 M saline; however, they did not change by perfusion of 0.3 M saline. Next, we examined the possible involvement of glutamate in the cardiovascular responses induced by hypertonic saline. Dizocilpine, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, attenuated the increases of blood pressure and heart rate, although 6-cyano-7-nitroquinoxaline-2,3-dione, an antagonist of the non-NMDA receptor, did not affect the blood pressure and heart rate. Our results show that local perfusion of the hypothalamic PVN region with hypertonic saline elicits a local release of glutamate, which may act via NMDA-type glutamate receptors to produce cardiovascular responses.

Animals↗
PubMed2000

Increase in norepinephrine but not nitric oxide metabolite levels in the hypothalamic paraventricular nucleus region in response to air jet and swing rotation in freely moving conscious rats.

Chronically instrumented, conscious rats were used to examine whether mild exteroceptive stress produces differential neurochemical changes in the hypothalamic paraventricular nucleus (PVN) region. We constructed systems for stress experiment of air jet and swing rotation that were conducted on freely moving conscious rats in a computer-controlled home cage. Concentration of extracellular norepinephrine (NE) and nitric oxide metabolites (NO(X)(-)), nitrite (NO(2)(-)) and nitrate (NO(3)(-)), in the PVN region was then measured by high-performance liquid chromatography with the respective detector; blood pressure (BP) and heart rate (HR) were also measured. Both stressors increased NE concentration in the PVN region as well as BP and HR. Neither stressor altered NO(X)(-) in the PVN region. Cardiovascular and NE changes showed reproducibility in intensity-dependent manner in response to repeated stressors. This finding demonstrated that exteroceptive stress produced different effects on the neurochemical mediators, NE and NO, in the PVN region.

Air↗
PubMed2000

GABA(A) and GABA(B) receptors modulating basal and footshock-induced nitric oxide releases in rat prefrontal cortex.

Using an in vivo brain microdialysis technique, we measured extracellular levels of nitric oxide (NO) metabolites (NO(x)(-)) in the medial prefrontal cortex (mPFC) upon perfusion of gamma-aminobutyric acid (GABA) receptor antagonists as well as agonists, and also examined the effects of GABA receptor agonists on mild intermittent footshock-induced NO releases in the mPFC in conscious rats. Perfusion of either bicuculline methiodide, a GABA(A) receptor antagonist, or saclofen, a GABA(B) receptor antagonist, through a microdialysis probe resulted in dose-dependent increases in NO(x)(-) levels. Higher-dose perfusion of either muscimol (50 microM), a GABA(A) receptor agonist, or baclofen (250 microM), a GABA(B) receptor agonist resulted in a significant decrease in NO(x)(-) levels. The elevated levels of NO(x)(-) after mild intermittent footshock were attenuated by perfusion of either muscimol (10 microM) or baclofen (50 microM), either of which alone did not affect basal NO(x)(-) levels. These findings are likely to provide helpful clues to our understanding of the inhibitory modulation of basal and footshock-induced NO metabolites releases by GABA(A) and GABA(B) receptors in the mPFC.

Animals↗
PubMed2000

Differential profiles of nitric oxide and norepinephrine releases in the paraventricular nucleus region in response to mild footshock in rats.

The purpose of this study was to determine whether the application of mild intermittent footshock stress can cause changes in the nitric oxide (NO) and norepinephrine (NE) releases in the hypothalamic paraventricular nucleus (PVN) region and medial prefrontal cortex (mPFC). Extracellular levels of NO metabolites and NE in the PVN region and mPFC were determined using an in vivo brain microdialysis technique in conscious rats. In the PVN region, we demonstrated that perfusion of N-methyl-D-aspartate through a microdialysis probe resulted in a dose-dependent increase in NO metabolite levels, whereas intraperitoneal administration of N(G)-nitro-L-arginine methyl ester produced a dose-dependent reduction in the levels of NO metabolites. The levels of NO metabolites in the PVN region increased after intraperitoneal administration of interleukin-1beta in a dose-dependent manner, as we previously reported. This increase in NO metabolite levels was abolished 60 min after systemic administration of N(G)-nitro-L-arginine methyl ester compared to the vehicle-treated control group. Twenty minutes of intermittent footshock induced NE release but did not induce NO release in the PVN region. On the contrary, in the mPFC, 20 min of intermittent footshock induced both NO and NE releases. The present results reveal different patterns and time courses in NO and NE releases between the PVN region and the mPFC in response to mild intermittent footshock stress. These findings are likely to have helpful suggestions for our understanding of the hypothalamic-pituitary-adrenal axis and the limbic forebrain system response to different kinds of stress.

Animals↗
PubMed2000

Activation of gastric afferents increases noradrenaline release in the paraventricular nucleus and plasma oxytocin level.

Effects of electrical stimulation of the gastric vagal nerves on plasma levels of oxytocin (OXT) and arginine vasopressin (AVP) were examined in rats anesthetized with urethane. Electrical stimulation of the gastric vagal nerves increased the plasma levels of OXT, but not AVP. The concentrations of extracellular noradrenaline (NA) in the paraventricular nucleus (PVN) were measured by in vivo microdialysis in rats anesthetized with urethane. Electrical stimulation of the gastric vagal nerves evoked an increase followed by a slight decrease in the concentrations of NA. The responses of spontaneous firing magnocellular neurosecretory neurons in the PVN to both electrical stimulation of the gastric vagal nerves and intravenous (i.v.) administration of CCK-8 were examined. Most of the putative OXT-secreting cells recorded were excited by both electrical stimulation of gastric vagal nerves and i.v. administration of CCK-8. These results suggest that gastric vagal afferents activate the central noradrenergic system from the brainstem to the PVN and secretion of OXT.

Afferent Pathways↗
PubMed2000

Fos expression in neurons immunoreactive for neuronal nitric oxide synthase in the rat paraventricular nucleus after intraperitoneal injection of interleukin-1 beta.

Double immunostaining for Fos and neuronal nitric oxide synthase (nNOS) was used to examine whether nNOS-immunoreactive neurons in the paraventricular hypothalamic nucleus (PVN) are activated to express Fos immunoreactivity by intraperitoneal injection of interleukin-1 beta (IL-1 beta) in the rat. Quantitative analysis revealed that some nNOS-positive PVN neurons are activated by IL-1 beta (4 microg/kg, i.p.) administration, but the majority of the IL-1 beta-activated PVN neurons do not express nNOS and are distributed mainly in the parvocellular part of the PVN.

Animals↗
PubMed2000

Discharge pattern of renal sympathetic nerve activity in the conscious rat: spectral analysis of integrated activity.

We investigated the periodic characteristics of bursting discharge in renal sympathetic nerve activity (RSNA) in conscious rats. Employing a discrete fast Fourier transform algorithm, a power spectrum analysis was used to quantify periodicities present in rectified and integrated RSNA whose signal-to-noise ratio in the recordings was greater than six. In conscious rats with intact baroreceptors, RSNA was characterized by four frequency components occurring at about 0.5, 1.5, 6, and 12 Hz, which corresponded to the low-frequency fluctuation of heart rate, respiration, and frequency of heart beat, and its harmonics, respectively. After intravenous infusion of sodium nitroprusside (SNP) to elicit reflex increases in RSNA and heart rate, the power for the component at 6 Hz followed the changes in heart beat frequency and was significantly increased, while those for the three other components were attenuated or experienced no change. In sino-aortic denervated (SAD) conscious rats, all four components were abolished, and the power spectrum was well fitted by a flat or Lorentzian curve, suggesting an almost random pattern. Only a respiratory-related component, which suggested common central modulation, appeared sporadically for short periods but was absent for the most part. Therefore most of this component together with the low-frequency component was also likely due to the baroreceptor-dependent peripheral modulation. The activity was sorted in 15 subgroups on the basis of spike amplitudes in the RSNA. Each subgroup showed frequency characteristics similar to the whole nerve activity. These results suggest that all periodicity in the RSNA of conscious rats with intact baroreceptors is caused by the baroreceptor input.

Action Potentials↗
PubMed2000

Voltage dependency of the frequency of slow waves in antrum smooth muscle of the guinea-pig stomach.

The effects of membrane depolarization on the frequency of spontaneous activities were investigated in circular smooth muscle of the guinea-pig antrum attached with (intact tissue) or without longitudinal muscles (circular tissue). Both types of tissue were spontaneously active; the intact tissues generated slow wave and circular tissues generated regenerative potential. The latter but not the former was abolished by caffeine. Increasing K(+) concentrations depolarized the membrane and reduced the amplitude and interval between spontaneous activities in both tissues; the amplitude was reduced linearly with depolarization and disappeared at about -35 mV; the interval was reduced successively with depolarization and reached a stable value (about 8 s) at about -45 mV. The depolarization and reduction in amplitude and interval of spontaneous activities induced by high K(+) solution were not altered by atropine, nitroarginine, or apamin in either tissue, suggesting that these changes did not involve the effects of neurotransmitters. The depolarization of the membrane by electrical stimulation also reduced the amplitude and interval of spontaneous activities in both tissues, in a potential-dependent way. The absolute refractory period for generation of the evoked regenerative potential was about 8 s, and the relative refractory period was 8--12 s. The results indicate that the frequency of slow waves increases with a depolarization of the membrane up to -45 mV, irrespective of the presence of caffeine-insensitive components. A depolarization of the membrane above -45 mV does not further increase the frequency of slow waves, possibly because of the refractory period for the generation of slow waves.

Animals↗
PubMed1999

Participation of arterial baroreceptors input and peripheral vasopressin in the suppression of renal sympathetic nerve activity induced by central salt loading in conscious rats.

We examined whether renal sympathetic nerve activity (RSNA) is suppressed in response to intracerebroventricular (i.c.v.) administration of hypertonic saline (HS) in conscious rats. RSNA was suppressed by i.c.v. administration of HS (0.3 M, 0.67 M, and 1.0 M, 1 microl/min for 20 min) in a concentration-dependent manner, which was attenuated under pentobarbital anesthesia. To elucidate mechanisms responsible for central HS-induced decrease in RSNA, possible involvement of arterial baroreceptors and peripheral arginine vasopressin (AVP) secreted from the posterior pituitary gland was examined using sinoaortic denervated (SAD) rats and non-peptide vasopressin receptor antagonists. The maximum suppression of RSNA (-81.5 +/- 5.5%) in control rats was significantly attenuated to -32.5 +/- 6.7% in SAD rats and to -55.8 +/- 5.7% in rats pretreated with intravenous vasopressin V1 receptor antagonist, OPC-21268 (5 mg/kg, i.v.). However, in SAD rats, pretreatment with vasopressin V1 receptor antagonist did not further affect the RSNA inhibition induced by central salt loading. The results suggest that the suppression of RSNA during central salt loading is mainly dependent on the arterial baroreceptors input and the 'additive' role of peripheral vasopressin.

Animals↗
PubMed1999

Nociceptin modulates renal sympathetic nerve activity through a central action in conscious rats.

Nociceptin, an endogenous agonist of the opioid receptor-like(1) receptor, is expressed in the hypothalamus, where it is implicated in autonomic nervous system control. However, the central actions of nociceptin on sympathetic nerve activity have not been studied. We investigated the effect of intracerebroventricularly administered nociceptin (2-10 nmol) on blood pressure, heart rate (HR), and renal sympathetic nerve activity (RSNA) in conscious rats and sinoaortic-denervated (SAD) rats. Intracerebroventricularly administered nociceptin resulted in a dose-dependent decrease in mean arterial pressure (MAP) and HR in intact rats. RSNA decreased 31.5 +/- 2.1 and 19.9 +/- 5.0% at a dose of 2 and 5 nmol, respectively. In SAD rats, MAP, HR, and RSNA decreased in a dose-dependent manner, and the maximum responses were larger than those in intact rats. The decrease in HR induced by nociceptin was blocked by propranolol but not by atropine, which indicates that nociceptin is acting by inhibiting cardiac sympathetic outflow. These nociceptin-induced depressor and bradycardic responses were not antagonized by pretreatment with naloxone and nocistatin. These findings suggest that central nociceptin may have a functional role in regulating cardiovascular and sympathetic nervous systems.

Animals↗
PubMed1999

Sympathetic and cardiovascular actions of orexins in conscious rats.

The novel hypothalamic peptides orexin-A and orexin-B are known to induce feeding behavior when administered intracerebroventricularly, but little is known about other physiological functions. The renal sympathetic nerves play important roles in the homeostasis of body fluids and the circulatory system. We examined the effects of intracerebroventricularly administered orexins on mean arterial pressure (MAP), heart rate (HR), renal sympathetic nerve activity (RSNA), and plasma catecholamine in conscious rats. Orexin-A (0.3, 3. 0 nmol) provoked an increase in MAP (94.3 +/- 0.7 to 101.9 +/- 0.7 mmHg and 93.1 +/- 1.1 to 108.3 +/- 0.8 mmHg, respectively) and RSNA (28.0 +/- 7.0 and 57.9 +/- 12.3%, respectively). Similarly, orexin-B (0.3, 3.0 nmol) increased MAP (93.9 +/- 0.9 to 97.9 +/- 0.9 mmHg and 94.5 +/- 1.1 to 105.3 +/- 1.7 mmHg, respectively). Orexin-A and -B at 3.0 nmol also increased HR. In other conscious rats, a high dose of orexin-A and -B increased plasma norepinephrine. Plasma epinephrine only increased with a high dose of orexin-A. These results indicate that central orexins regulate sympathetic nerve activity and affect cardiovascular functions.

Animals↗
PubMed1999

Centrally administered murine leptin stimulates plasma arginine-vasopressin secretion and increases the level of mRNA expression in the supraoptic nucleus of conscious rats.

The product of the ob gene protein, leptin, has been suggested to function as an endogenous mediator of the cardiovascular system via sympathetic nerve activity. Moreover, extensive distribution of leptin receptor-like immunoreactivity has been demonstrated in the choroid plexus, cerebral cortex, hippocampus, thalamus and hypothalamus, especially in the paraventricular nucleus (PVN) and supraoptic nucleus (SON). In this study, we have investigated the in vivo effects of leptin on plasma arginine-vasopressin (AVP) secretion and the level of AVP messenger ribonucleotic acid (AVP mRNA) in the SON of conscious rats. Intracerebroventricularly administered leptin increased plasma AVP concentration in a dose-dependent manner (0-400 pmol/rat). The maximal effect was obtained at 15 min after the administration of leptin. Furthermore, in Northern blot analyses, the levels of AVP mRNa in the SON increased approximately 2-fold from the basal level after the administration of leptin. AVP mRNA expression in the PVN was also increased by leptin. However, leptin had no effects on plasma oxytocin (OXT) secretion and OXT gene expression in the SON. In conclusion, leptin is involved in AVP secretion via the central nervous system, however, its physiological role is unknown.

Animals↗
PubMed1998

Cardiovascular and sympathetic effects of proadrenomedullin NH2-terminal 20 peptide in conscious rats.

Proadrenomedullin NH2-terminal 20 peptide (PAMP) and adrenomedullin (AM), which are derived from the same gene, are novel vasodilative peptides and have been shown to exhibit hypotensive action in anesthetized animals. To avoid the modification via anesthesia, we investigated the effects of intravenously administered PAMP on mean arterial pressure, heart rate (HR), and renal sympathetic nerve activity (RSNA) relative to those of AM in conscious unrestrained rats. We also examined whether the arterial baroreceptor reflex was altered with the two peptides. Intravenous injection of rat PAMP (rPAMP) (10, 20 and 50 nmol/kg) and rat AM (rAM) (0.3, 1.0 and 3.0 nmol/kg) similarly elicited dose-related hypotension accompanied by increases in HR and RSNA. However, the responses to rPAMP were less potent in magnitude and shorter in duration than those to rAM. Moreover, rAM facilitated baroreflex control, whereas rPAMP attenuated it. These findings indicate that although PAMP, as well as AM, may play an important role as a circulating hormone in the systemic circulation of conscious rats, the two peptides derived from an identical origin might have different mechanisms responsible for their cardiovascular and RSNA actions.

Adrenomedullin↗
PubMed1998

Differential effects of anesthetics on sympathetic nerve activity and arterial baroreceptor reflex in chronically instrumented rats.

The effects of pentobarbital sodium, chloralose, and urethane on sympathetic nerve activity and arterial baroreceptor reflex were examined using rats chronically instrumented for recordings of blood pressure (BP), electrocardiogram and renal sympathetic nerve activity (RSNA). Pentobarbital sodium (30 mg/kg, i.v.) produced a decrease in BP with a transient decrease in heart rate (HR) and no change in RSNA. Chloralose (50 mg/kg, i.v.) also caused a decrease in BP and no change in HR and RSNA until a later increase in HR and RSNA, while urethane (800 mg/kg, i.v.) increased BP, HR, and RSNA. Baroreceptor reflex function was assessed by constructing a logistic function curve compiled from data obtained by intravenous infusion in increasing doses of phenylephrine and sodium nitroprusside. Both pentobarbital sodium and chloralose administration decreased the gain of baroreceptor reflex control of both HR and RSNA. Urethane also decreased the gain of baroreceptor reflex control of HR but elicited no change in that of RSNA. These results suggest that different intravenously administered anesthetics affect the peripheral sympathetic outflows in qualitatively and quantitatively different manners.

Anesthetics↗
PubMed1998

Abdominal vagotomy attenuates interleukin-1 beta-induced nitric oxide release in the paraventricular nucleus region in conscious rats.

Nitric oxide (NO) has recently been shown to modulate the hypothalamic-pituitary-adrenal axis response to interleukin-1 beta (IL-1 beta). We measured levels of nitrite (NO2-) and nitrate (NO3-) in the hypothalamic paraventricular nucleus (PVN) region using an in vivo brain microdialysis technique in conscious rats. Intraperitoneally administered IL-1 beta produced a significant increase in both NO2- and NO3- levels in the PVN region. We also examined the possible involvement of the abdominal vagal afferent nerves in this effect. In abdominal-vagotomized rats, the increase was significantly attenuated compared to that in sham-operated rats. Our results suggest that the abdominal vagal afferent nerves are involved in intraperitoneally administered IL-1 beta-induced NO release in the PVN region.

Abdomen↗