BACKGROUND: One of prominent cardiovascular effects of imipramine is postural hypotension. The present study was to verify whether imipramine has a central hypotensive action and futher to investigate its mechanism of action. METHODS: Rats(male, Sprague-Dawley) weighing 250-300g were anesthetized with pentobarbital sodium(50mg/kg, ip). Imipramine was administered into the left lateral cerebral ventricle. Mean arterial pressure(MAP) and heart rate(HR) were continuously monitored from the right femoral artery. RESULTS: Intracerebroventricular(icv) imipramine(3micromol/kg) caused decrease in MAP without significant alterations in HR, of which safety dose-range was very narrow. 1micromol/kg did not affect MAP and 10micromol/kg caused deaths of animals within 10min. Intravenous infusion of the same dose(3micromol/kg) of imipramine caused only a transient hypotension within 5min. Hexamethonium-treated(1mg/kg/min) rats did not respond to icv imipramine. Regitine pretreatment(2mg/kg, iv) prevented the hypotensive response to icv imipramine. Yohimbine pretreatment(500microg/kg, icv) not only blocked the hypotensive effect, but it caused a transient pressor response to icv imipramine. CONCLUSIONS: These results indicate that imipramine has a separate hypotensive effect which is mediated through central alpha2-adrenoceptors.
Animals ; Blood Pressure ; Cerebral Ventricles ; Femoral Artery ; Heart ; Hypotension ; Hypotension, Orthostatic ; Imipramine* ; Infusions, Intravenous ; Pentobarbital ; Phentolamine ; Rats* ; Yohimbine

BACKGROUND: Prostaglandin system is known to participate in manifestation of the renin-angiotensin system. However, role of prostaglandins on the renin-angiotensin system in development of hypertension is not well established. This study was to examine whether the role of prostaglandins is altered in experimental hypertension. METHODS: Two-kidney, one-clip(2KIC) renal hypertension was made by clipping the left renal artery with a silver clip(internal gap of 0.2mm) and deoxycorticosterone acetate (DOCA)-salt hypertension by subcutaneous implantation of DOCA(200mg/kg) strip plus saline(1%) drinking. They were used 3 weeks later. Age-matched normal rats served as a control. Femoral artery was cannulated and arterial blood pressure and heart rate were monitored continuously. RESULTS: 1) In normotensive rats, saralasin infusion(20 microg/kg/min, IV) caused a decrease in mean arterial pressure without significant alterations in heart rate. Indomethacin-pretreatment(10mg/kg, IP) abolished the depressor response to saralasin. 2) The depressor response to saralasin was more marked in renal hypertensive rats than in normotensive rats. The magnitude of maximum decrease in blood pressure, however, was comparable between the hypertensive and normotensive rats. Indomethacin-pretreatment did not affect the depressor response to saralasin in renal hypertensive rats. 3) In DOCA-salt hypertensive rats, saralasin infusion rather caused an increase in mean arterial pressure without significant alterations in heart rate. The pressor response to saralasin was not affected by indomethacin-pretreatment. CONCLUSION: These results indicate that prostaglandin system may modify renin-angiotensin system in normotensive rats. It is suggested that mechanisms other than prostaglandin system participate in the full-blown manifestation of renin-angiotensin system in 2KIC renal hypertensive rats.
Animals ; Arterial Pressure ; Blood Pressure ; Desoxycorticosterone ; Drinking ; Femoral Artery ; Heart Rate ; Hypertension ; Hypertension, Renal ; Prostaglandins I ; Prostaglandins* ; Rats* ; Renal Artery ; Renin-Angiotensin System* ; Saralasin ; Silver

BACKGROUND: Aside from its well known peripheral antihypertensive effects, calcium also lowers blood pressure, when administered into the cerebral ventricle. The present study was aimed to determine whether the central depressor response to calcium is mediated by a stimulation of endogenous L-arginine-nitric oxide (NO) pathway. METHODA: Mean arterial pressure (MAP) and heart rate (HR) were continuously recorded from the femoral artery in anesthetized rats. Administration of calcium was performed into the right lateral cerebral ventricle. The effects of N G-nitro-L-arginine methyl ester (L-NAME) on the cardiovascular response to calcium were examined. RESULTS: Intracerebroventricular (ICV) injection of calcium consistently produced a decrease in MAP and HR. The depressor and bradycardiac responses to calcium showed a dose-dependent fashion. Pretreatment with a calcium channel blocker, diltiazem (1 micromol, ICV), attenuated cardiovascular responses to calcium. ICV infusion (1 microl/min) of L-NAME (200 microgram/kg and 20 microgram/kg/min for 60 min) increased MAP without significant changes in HR. Chronic ingestion of L-NAME (5 mg/100 ml in drinking water, 4 weeks) also increased the systolic blood pressure as compared with control. The depressor effect of ICV calcium was significantly diminished in acute or chronic L-NAME treated rats. CONCLUSION: These findings suggest that the central depressor response to calcium, at least in part, is NO-dependent.
Animals ; Arterial Pressure ; Blood Pressure ; Calcium Channels ; Calcium* ; Cerebral Ventricles ; Diltiazem ; Drinking Water ; Eating ; Femoral Artery ; Heart Rate ; NG-Nitroarginine Methyl Ester ; Nitric Oxide* ; Rats

Diagnosis of a thymic carcinoid was made on transthoracic fine needle aspiration in a 36-year old woman who had an anterior mediastinal mass on chest X-ray and CT scan. The aspiration smears showed numerous anastomosing ribbons and cords of small round tumor cells. The tumor cells had slightly eccentric nuclei and some granular cytoplasm. The small and uniform nuclei of the tumor cells had finely granular chromatin and thin nuclear membrane. The cytologic diagnosis of a carcinoid was confirmed on histopathologic, immunohistochemical, and electromicroscopic examination of surgical specimen.
Adult ; Alleles* ; Biopsy, Fine-Needle ; Carcinoid Tumor ; Carotid Body ; Child* ; Chromatin ; Cytoplasm ; Diagnosis ; Female ; Humans ; Immunoglobulin A* ; Nuclear Envelope ; Paraganglioma ; Thorax ; Tomography, X-Ray Computed

Although many studies show that thromboxane A2 (TXA2) has the action of gastrointestinal (GI) motility using GI muscle cells and tissue, there are no reports on the effects of TXA2 on interstitial cells of Cajal (ICC) that function as pacemaker cells in GI tract. So, we studied the modulation of pacemaker activities by TXA2 in ICC with whole cell patch-clamp technique. Externally applied TXA2 (5 micrometer) produced membrane depolarization in current-clamp mode and increased tonic inward pacemaker currents in voltage-clamp mode. The tonic inward currents by TXA2 were inhibited by intracellular application of GDP-beta-S. The pretreatment of ICC with Ca2+ free solution and thapsigargin, a Ca2+-ATPase inhibitor in endoplasmic reticulum, abolished the generation of pacemaker currents and suppressed the TXA2-induced tonic inward currents. However, chelerythrine or calphostin C, protein kinase C inhibitors, did not block the TXA2-induced effects on pacemaker currents. These results suggest that TXA2 can regulate intestinal motility through the modulation of ICC pacemaker activities. This modulation of pacemaker activities by TXA2 may occur by the activation of G protein and PKC independent pathway via extra and intracellular Ca2+ modulation.
Animals ; Benzophenanthridines ; Endoplasmic Reticulum ; Gastrointestinal Motility ; Gastrointestinal Tract ; GTP-Binding Proteins ; Guanosine Diphosphate ; Interstitial Cells of Cajal ; Intestines ; Membranes ; Mice ; Muscle Cells ; Naphthalenes ; Patch-Clamp Techniques ; Protein Kinase C ; Thapsigargin ; Thionucleotides ; Thromboxane A2

BACKGROUND: An increase of the extracellular K+concentrations up to about 8 mM in the isolated vessels causes relaxation in pre-contracted state. In order to elucidate the mechanisms of K+induced relaxation and compare with that of 2-kidney, 1 clip (2K1C) renal hypertensive rats, we recorded aortic vascular tension using an organ bath study. METHOD: 2K1C hypertension was made by clipping the left renal artery and age-matched control rats received a sham treatment. Thoracic aortic rings were mounted in tissue baths for measurement of isometric contractile force. RESULTS: Exposure to K+(from 2 to 8 mM) relaxed a phenylephrine (2 x 10-6 M)-induced contraction in K+free Krebs-Ringer solution, dose-dependently. Ouabain (10-5 M) enhanced the K+induced relaxation in above 2 mM K+ The K+induced relaxation was still induced in endothelium-denuded condition. Incubation with the K+channel blockers such as tetraethylammonium (TEA, 1 mM), glibenclamide (10-5 M), 4-aminopyridine (3 mM), barium (5 mM) and cesium (2 mM) did not affect on the K+induced relaxation. In renal hypertensive rats, the K+induced relaxation was markedly suppressed and ouabain enhanced it. CONCLUSIONS: These results suggest that the K+induced relaxation in aorta be mediated by Na-pump independent mechanisms, and the decrease of the K+induced relaxation in the renal hypertensive rats may be a possible mechanism of hypertension.
4-Aminopyridine ; Animals ; Aorta ; Barium ; Baths ; Cesium ; Glyburide ; Hypertension ; Muscle, Smooth* ; Ouabain ; Phenylephrine ; Placebos ; Rats* ; Relaxation ; Renal Artery ; Tetraethylammonium ; Vasodilation*

BACKGROUND: An increase of the extracellular K+concentrations up to about 8 mM in the isolated vessels causes relaxation in pre-contracted state. In order to elucidate the mechanisms of K+induced relaxation and compare with that of 2-kidney, 1 clip (2K1C) renal hypertensive rats, we recorded aortic vascular tension using an organ bath study. METHOD: 2K1C hypertension was made by clipping the left renal artery and age-matched control rats received a sham treatment. Thoracic aortic rings were mounted in tissue baths for measurement of isometric contractile force. RESULTS: Exposure to K+(from 2 to 8 mM) relaxed a phenylephrine (2 x 10-6 M)-induced contraction in K+free Krebs-Ringer solution, dose-dependently. Ouabain (10-5 M) enhanced the K+induced relaxation in above 2 mM K+ The K+induced relaxation was still induced in endothelium-denuded condition. Incubation with the K+channel blockers such as tetraethylammonium (TEA, 1 mM), glibenclamide (10-5 M), 4-aminopyridine (3 mM), barium (5 mM) and cesium (2 mM) did not affect on the K+induced relaxation. In renal hypertensive rats, the K+induced relaxation was markedly suppressed and ouabain enhanced it. CONCLUSIONS: These results suggest that the K+induced relaxation in aorta be mediated by Na-pump independent mechanisms, and the decrease of the K+induced relaxation in the renal hypertensive rats may be a possible mechanism of hypertension.
4-Aminopyridine ; Animals ; Aorta ; Barium ; Baths ; Cesium ; Glyburide ; Hypertension ; Muscle, Smooth* ; Ouabain ; Phenylephrine ; Placebos ; Rats* ; Relaxation ; Renal Artery ; Tetraethylammonium ; Vasodilation*

Bradykinin has been known to elicit a pressor effect when administered centrally, and a depressor effect when administered peripherally. The present study was aimed at investigating whether the blood pressure response to bradykinin is dependent on the endogenous generation of nitric oxide (NO). Effects of NG-nitro-L-arginine methyl ester (L-NAME) on the pressor and depressor responses to intracerebroventricularly and intravenously injected bradykinin (5nmol/rat), respectively, were examined in anesthetized rats. Neither the pressor response nor the depressor response was affected by acute parenteral treatment with L-NAME. The pressor and depressor effects of bradykinin were also noted in rats chronically supplemented with L-NAME in drinking water for 4 weeks. Bradykinin caused a relaxation of the isolated thoracic aorta in vitro, which was not affected in the presence of L-NAME. However, bradykinin failed to cause a relaxation of the aorta isolated from rats chronically treated with L-NAME. These findings suggest that endogenous generation of NO may not completely account for the blood pressure responses to bradykinin in rats.
Animals ; Aorta ; Aorta, Thoracic ; Blood Pressure* ; Bradykinin* ; Drinking Water ; NG-Nitroarginine Methyl Ester ; Nitric Oxide* ; Rats* ; Relaxation

BACKGROUND: The sodium concentration in the central nervous system may play an important role in cardiovascular function and body fluid regulation. The purpose of this investigation was to examine the effects of intracerebroventricular (ICV) infusion of hypertonic NaCl solutions on the cardiovascular responses in normotensive and 2-kidney, 1 clip (2K1C) renal hypertensive rats. METHODS: 2K1C hypertension was made by clipping the left renal artery and were used 4 weeks later. Age-matched control rats received a sham treatment. Under thiopental (50 mg/kg, IP) anesthesia, both isotonic and hypertonic NaCl solutions (0.15 M, 0.6 M and 1.2 M) were ICV applied, while blood pressure and heart rate (HR) responses were continuously monitored. RESULTS: Central administration of hypertonic NaCl solution caused an elevation in mean arterial pressure (MAP) and HR in both normotensive and 2K1C hypertensive rats. The response magnitude in the blood pressure was positively correlated to the NaCl concentration in normotensive rats, while the pressor responses to hypertonic NaCl were comparable regardless of the concentration of NaCl in hypertensive rats. Despite of the HR responses were similar in between two groups, the magnitude of the MAP increases were more elevated in hypertensive than in normotensive control rats. Isotonic NaCl solution, when centrally applied, caused an elevation in blood pressure only in hypertensive rats. CONCLUSION: These results indicate that the central sensitivity to sodium chloride is altered in 2K1C renal hypertensive rats.
Anesthesia ; Animals ; Arterial Pressure ; Blood Pressure ; Body Fluids ; Central Nervous System ; Heart Rate ; Hypertension ; Hypertension, Renal ; Infusions, Intraventricular* ; Placebos ; Rats* ; Renal Artery ; Sodium ; Sodium Chloride ; Thiopental

Tyrosine kinases have been implicated in vascular smooth muscle cell proliferation and contraction. The involvement of tyrosine kinases in 5-hydroxytryptamine (5-HT)-induced contractile response of the isolated aorta was examined in two-kidney, one clip (2K1C) hypertensive rats, 2141C hypertension was made by constricting the left renal artery and age-matched control rat received sham treatment. Thoracic aortic rings denuded of endotheliurn were mounted in tissue bath, for measurement of isometric contractile force. The putative tyrosine kinase inhibitor, genistein, shifted concentration-response curves to 5-HT toward the right in control rats The isometric force generation induced by 5-HT was also inhibited by genistein in aortic rings from 2K1C: hypertensivc rats, however genistein did not affect on the high concentration of 5-HT in hypertensive rat ;. Genistein-induced relaxations were more attenuated in aortae from hypertensive rats than those from control Genistein had no effect on contrartcion elicited by the direct protein kinase C activator, phorbol 12, 13 dibutyrate (PDBu) either in 2KlC hypertensive or in control Group. These findings indicate that genistein-sensitive tyrosine kinases paeticipate in 5-HT-induced contraction of rat aortic smooth muscle, of which role is apparent in 2K1C: hypertension.
Animals ; Aorta ; Baths ; Cell Proliferation ; Genistein ; Hypertension ; Muscle, Smooth ; Muscle, Smooth, Vascular ; Phosphotransferases* ; Placebos ; Protein Kinase C ; Protein-Tyrosine Kinases ; Rats* ; Relaxation ; Renal Artery ; Serotonin ; Tyrosine*