山﨑 将生

Background: Pulse wave velocity, conventionally determined between the carotid and femoral arteries, is a useful measure to estimate stiffness of the aorta. We investigated local pulse wave velocity (LPWV) in different segments in the aorta with relatively early-stage atherosclerosis in relation to the extent and severity of atherosclerotic lesions. Methods: Pressure waves were recorded in eight aortic positions using two catheters with one or two micromanometers to determine LPWV in the ascending aorta, distal end of the aortic arch, proximal, middle, and distal thoracic aortas, and proximal, middle, and distal abdominal aortas in Kurosawa and Kusanagi-hypercholesterolemic (KHC) and normal rabbits aged 10 to 12 months. Results: The LPWV in the KHC rabbit was greatest in the aortic arch, decreased almost to the normal level in the middle and distal thoracic aorta, increased in the proximal abdominal aorta, and showed almost identical change to that in the normal rabbit in the middle and distal abdominal aortic regions. There was significant difference in LPWV in the aortic arch, proximal thoracic, and proximal abdominal aortas between the two rabbit groups. The sclerotic lesion was prominent in the aortic arch, proximal thoracic aorta, and proximal abdominal aortas. The wall was severely thickened with abundant foam cells. The significant increase in LPWV would be mainly related to the increased wall thickness in these aortic regions. Conclusions: We can conclude that LPWV reflects well the distribution and severity of atherosclerotic lesion and the increased wall thickness in the local aortic region in which pulse waves were traveled. (C) 2004 American Journal of Hypertension, Ltd.

Hydrostatic pressure gradients due to the gravitational force in blood vessels disappear under conditions of microgravity during spaceflight, and the ability of the baroreceptor reflex to control arterial pressure and blood distribution may be altered. We hypothesized, on the basis of the results obtained in our previous experiments using the head-down tilt method in rats and rabbits, that the range of increase in arterial pressure caused by animal behavior narrows under conditions of microgravity, affecting the development of high-threshold unmyelinated fibers in the rat aortic nerve which sends signals from baroreceptors located in the aortic wall to the reflex center. We verified this hypothesis using 9-day-old rat neonates housed with their dams for 16 days on the space shuttle Columbia in outer space (STS-90, Neurolab Mission). Age-matched neonatal rats with the dams remained on the ground as controls. After breeding was carried out in the three experimental groups (FLT, spaceflight; AGC, asynchronous ground control; VIV, vivarium ground control), specimens of the 25-day-old rats were excised and five left aortic nerves in each group were examined by electron microscopy. The number of aortic unmyelinated fibers was significantly less in the FLT group than in each ground control (mean+/-S.D.; 139+/-37 in the FLT, 207 36 in the AGC, 283+/-121 in the VIV; P<0.05), which may be related to the weakness of the baroreceptor reflex under conditions of microgravity in space. This result may contribute to understanding of the several cardiovascular issues which occur under microgravity and after reexposure to gravity in human. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.

The present study is designed to investigate the time-dependent effect of pentobarbital anesthesia on the baroreflex arterial pressure (AP) control system in rabbits. The overall AP control capacity of the baroreflex system was assessed with mean arterial pressure (MAP) responses to the rapid mild hemorrhage (2 ml/kg body weight) and an overall open-loop gain (G) of the system. The G value was determined by means of the following formula: G=ΔAPl/ΔAPs-1, where ΔAPl is an immediate MAP fall and ΔAPs a steady-state fall after the rapid hemorrhage. Prior to the experiment, two catheters for AP measurement and hemorrhage were chronically in-dwelt in the aortic arch via the left subclavian and left common carotid arteries, respectively. Control mean arterial pressure averaged for 30 sec before the rapid hemorrhage (CMAP), ΔAPl and ΔAPs significantly increased and reached the maximal value at 14 min (CAMP: p&lt 0.01) and 28 min (ΔAPl: p&lt 0.01 and ΔAPs: p&lt 0.01) after the intravenous injection of sodium pentobarbital in a 25.0 mg/kg dose, respectively. These values gradually decreased in the course of time and tended to recover to near the preanesthetic level at 77-98 min after the anesthesia. The G value significantly decreased from 7.3 in the conscious state to 1.5 at 28 min after the anesthesia (p&lt 0.001), gradually increased with lapse of time and recovered to near the preanesthetic level at 77-98 min after the anesthesia. No significant difference in G was observed between in the conscious and anesthetized states beyond 70 min after the anesthesia (p&gt 0.05). These findings suggest that pentobarbital sodium exerts a time-dependent inhibitory effect on the baroreflex system but does not significantly affect the overall AP control capacity of the baroreflex system itself at least 70 min after the intravenous administration at a dose of 25.0 mg/kg.

We investigated to determine whether or not the inhibitory M(2)-receptors function in the rabbit lung and heart. Rabbits were anesthetized, vagotomized, paralyzed and ventilated. Administration of gallamine, an M(2)-receptor antagonist, augmented an increase of P-T produced by vagal stimulation with or without simultaneous administration of histamine and the increases were dose-dependent. Conversely, prior treatment with pilocarpine, an M(2)-receptor agonist, reduced these responses in a dose-dependent manner. The P-T responses to histamine injection only were not significantly altered by administration of either gallamine or pilocarpine. The remaining bronchoconstrictor responses to the three stimuli in the presence of gallamine or pilocarpine were completely blocked by atropine. In another series of experiments, gallamine treatment enhanced bronchoconstriction evoked by vagal stimulation but reduced acetylcholine (ACh)-induced bronchoconstriction. These opposite responses were dose-dependent for gallamine. The results suggest that there are inhibitory M(2)-receptors in the parasympathetic nerves innervating the lungs in the rabbit. Furthermore, gallamine treatment that completely blocked bradycardia evoked by ACh administration reduced vagally-mediated bradycardia. This implies that gallamine appears to have an antagonistic action on muscarinic receptors in the rabbit heart.

We studied the effects of aerosol administration of veratridine (a sodium channel opener) or nifedipine (a calcium channel blocker) on the responses of rapidly adapting pulmonary stretch receptors (RARs) and dynamic lung compliance (Cdyn) to aerosols of 2 and 4% ammonia solutions in anesthetized spontaneously breathing rabbits without intact vagi. The RARs increased their activity following ammonia aerosol, and the increase was concentration-dependent. However, ammonia aerosol did not significantly alter the value of Cdyn. The RARs following aerosol administration of veratridine (about 200 mu g) showed their characteristic firing pattern with several phases; each phase was characterized by the long high-frequency continuous discharges. Under these conditions, the response was not associated with any significant change in Cdyn. Even though the change in receptor activity produced by veratridine was restored to control level, subsequent aerosol application of ammonia led to similar firing patterns, as veratridine was given by aerosol, but had no significant effect on Cdyn. Following aerosol administration of nifedipine (about 1 and 2 mg) the RAR activity and Cdyn were similar to those during control. Furthermore, the ammonia-induced RAR stimulation was not significantly affected by nifedipine aerosol. These results suggest that the stimulation of RARs by ammonia in vagotomized rabbits is independent of changes in Cdyn and speculate that their excitatory effect is at least in part related to the activation of Na+ influx to the receptive terminals but is not involved in the secondary entry of Ca2+ ions to the receptor membrane, through voltage-dependent calcium channels.

We investigated the effects of the substance P (SP) blocker [D-Pro(2),D-Trp(7,9)]-SP on the response of rapidly adapting pulmonary stretch receptors (RARs) to SP administered into the right atrium, or ammonia vapor inhaled into the lungs in anesthetized, spontaneously breathing rabbits. Right atrial administration of SP (0.3, 1.0, and 3.0 mu g/kg) caused an increase in the RAR activity, and this increase became more prominent as the dose of SP was increased. The RARs Increased their activity following inhalation of vapor from 5 and 10% ammonia solutions, and the increase was concentration dependent. The excitatory responses of RAR activity to SP al different doses were greatly diminished or completely blocked by administration of the selective SP antagonist (300 and 500 mu g/kg). However, the ammonia-induced RAR stimulation was not significantly altered by prior treatment with the SP blocker (300 and 500 mu g/kg). These results suggest that the stimulation of RARs by ammonia does not occur as a result of the release of SP from sensory nerves in the airways and lungs.

Studies were designed to establish the difference of the excitatory mechanisms between histamine and ammonia on rapidly adapting pulmonary stretch receptors (RARs). We therefore examined the responses of RARs to histamine administered as an aerosol and ammonia inhaled as a vapor before and after aerosol administration of mequitazine or cimetidine in spontaneously breathing rabbits. The excitatory responses of RARs to aerosols of histamine at different concentrations were completely blocked by administration of aerosol mequitazine but potentiated by aerosol cimetidine. However, the increases of RAR activity produced by inhalation of ammonia vapor at different concentrations were not significantly affected by aerosol administration of either a H-1-receptor blocker or a H-2-receptor antagonist. These results suggest that the stimulation of RARs by aerosol histamine occurs as a result of the interaction between H-1 (excitatory)- and H-2 (inhibitory)-receptor effects, whereas these two receptor effects do not contribute to the ammonia-induced RAR stimulation.