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BACKGROUND The Morning Hypertension and Angiotensin Receptor Blocker/Hydrochlorothiazide Combination Therapy (MAPPY) study has shown that losartan/hydrochlorothiazide (HCTZ) combination is superior to high-dose losartan in not only reducing morning systolic blood pressure (SBP) but also ameliorating urinary albumin excretion (UAE) after 3-month treatment. The purpose of the present study was to investigate factors associated with UAE reduction in on-treatment patients with morning hypertension. METHODS AND RESULTS A total of 95 patients registered in the MAPPY study were analyzed. Patients were treated with either a losartan/HCTZ combination regimen (n=47) or a high-dose losartan regimen (n=48). Three-month treatment significantly reduced morning SBP, evening SBP, and clinic SBP (P

Randomized clinical trials have demonstrated that coronary stenting is more successful than balloon angioplasty in improving short- and long-term outcomes. However, it remains unknown whether those results can be generalized to broad-based practice. This study aimed to determine whether the outcome for patients with acute myocardial infarction (AMI) undergoing coronary stent placement would be better than those undergoing balloon angioplasty. The risk-adjusted mortality and subsequent revascularization rates were compared for 2,185 patients from a nationwide Japanese registry during 1997. A total of 1,349 patients were treated with balloon angioplasty alone and 836 had stent placement. There were no statistically significant differences in the prevalence of demographic, clinical, and angiographic variables, except that the angioplasty group had a greater proportion of female patients and those with a left circumflex lesion. Unadjusted in-hospital mortality was comparable (7.6 vs 6.3%; p=0.28), despite higher angiographic success rate for the stent group (89.7 vs 97.7%; p

A survey by the Japanese Coronary Intervention Study (JCIS) group revealed that 109,788 percutaneous coronary intervention (PCI) procedures were performed at 1,023 laboratories during 1997. The present study aimed to describe the demographic and clinical characteristics, treatment strategies, in-hospital outcomes, and long-term outcomes of these patients. A total of 10,642 PCIs performed in 8,814 patients, which corresponded to approximately 10% of the overall PCIs, were selected at random. The mean patient age was 65 years, and 75% were males. The patients often had extensive coronary risk factors. The most prevalent clinical diagnosis was stable angina (36%), followed by myocardial infarction (MI) excluding acute myocardial infarction (AMI; 28%) and AMI (25%). Plain old balloon angioplasty was used as the sole procedure in 58% of lesions for which an attempt to heal was made, and coronary stent placement in 38%. Angiographic success was achieved in 92% of attempted lesions. Mortality, MI and emergency coronary artery bypass grafting (CABG) rates during the hospitalization were 2.6%, 2.0% and 0.7%, respectively. In-hospital mortality rate for AMI was 7.6%, whereas that for elective PCI in cases without AMI was 0.6%. The overall mortality for 1.8 years was 8%. Repeat PCI was performed for 35% and CABG for 6% during the follow-up period. In Japan, PCI was performed in patients with coronary artery disease and extensive risk factors, but a high rate of angiographic success was achieved. The rates of in-hospital mortality and emergency CABG were low in non-AMI patients, but the 1-year rate of repeat PCI was as high as 32%.

We previously demonstrated that endothlin-1 (ET-1) augments and ETA receptor antagonist attenuates excitatory neuronal response to glutamate (Glu) in brainstem slices from normotensive rats. The aim of this study was to determine which type of Glu receptor is responsible for the stimulatory effects of ET-1 on neurons of the nucleus tractus solitarii (NTS). Single unit discharges were recorded extracellularly from rat brainstem slice preparations. Seven NTS neurons that were excited by solitary tract (ST) stimulation responded to iontophoretically applied ET-1 with neuronal activity. An N-methyl-D-aspartate (NMDA) receptor antagonist, non-NMDA, 6-cyano-7-nitro-quinoxaline-2, 3-dione (CNQX), or DL-2-amino-5-phosphonovaleric acid (AP-5) was perfused over the slices with Kreb’s-Ringer solution. The increase in neuronal activity evoked by iontophoretically applied ET-1 was nearly abolished by CNQX but not by AP-5. CNQX but not AP-5 decreased the basal spontaneous neuronal activity of NTS neurons. These results suggest that non-NMDA receptors play a role in mediating the stimulatory effect of ET-1 on neuronal activity in the NTS. (Hypertens Res 2001; 24: 137-142)

A nation-wide survey on the procedures and facilities of coronary revascularization, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) conducted by the Japanese Coronary Intervention Study (JCIS) group during 1997 revealed that PCI is more often used than CABG and is mainly carried out in low-volume facilities without surgical backup. The present study aimed to investigate the temporal changes in the usage of revascularization therapies and facilities from 1997 to 1999. A questionnaire was mailed in 1998 to the delegates of 1,086 PCI and 582 CABG facilities identified by the previous survey, and 89% of PCIs surveyed and 94% of CABGs surveyed reported back. The number of PCI procedures had increased by 19% from 97,831 to 116,479 and that of CABG procedures also increased by 21% from 16,374 to 19,846. The ratio of PCI to CABG was 5.9 in 1999, showing no significant change from 6.0 in 1997. In parallel, the number of PCI and CABG facilities increased from 888 to 941 and from 442 to 453, respectively. The use of coronary stents and other interventional devices increased during these 2 years. Coronary stents were used regardless of the annual procedural volume of the facilities, whereas other interventional devices, directional and rotational coronary atherectomy, were used mainly in the high-volume laboratories (p

A nation-wide survey on the procedures and facilities of coronary revascularization, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) conducted by the Japanese Coronary Intervention Study (JCIS) group during 1997 revealed that PCI is more often used than CABG and is mainly carried out in low-volume facilities without surgical backup. The present study aimed to investigate the temporal changes in the usage of revascularization therapies and facilities from 1997 to 1999. A questionnaire was mailed in 1998 to the delegates of 1,086 PCI and 582 CABG facilities identified by the previous survey, and 89% of PCIs surveyed and 94% of CABGs surveyed reported back. The number of PCI procedures had increased by 19% from 97,831 to 116,479 and that of CABG procedures also increased by 21% from 16,374 to 19,846. The ratio of PCI to CABG was 5.9 in 1999, showing no significant change from 6.0 in 1997. In parallel, the number of PCI and CABG facilities increased from 888 to 941 and from 442 to 453, respectively. The use of coronary stents and other interventional devices increased during these 2 years. Coronary stents were used regardless of the annual procedural volume of the facilities, whereas other interventional devices, directional and rotational coronary atherectomy, were used mainly in the high-volume laboratories (p

We previously demonstrated that endothelin-1 (ET-1) increases the neuronal activity of neurons in the nucleus tractus solitarii (NTS) and augments the response to glutamate (Glu), using in vitro brainstem slice preparations of normotensive Wistar-Kyoto (WKY) rats. This study was designed to determine whether the effects of ET-1 on neuronal activity and synaptic transmission in the NTS are altered in spontaneously hypertensive rats (SHR). Experiments were performed with WKY rats and age-matched SHR. We recorded the extracellular single unit of neuronal activity of NTS neurons in response to electrical stimulation of the solitary tracts using in vitro brainstem slice preparations. ET-1 or Glu was iontophoretically applied to the recording neurons. ET-1 increased the neuronal activity of NTS neurons in SHR as well as WKY. The magnitude of the increase in the neuronal activity evoked by Glu was augmented by application of ET-1 in WKY rats (6.1±0.6 to 11.1±1.7spikes/s, p

The aims of this study were to determine 1) whether endothelin (ET)-1 affects the neuronal activity of the NTS neurons, 2) whether specific ET receptor antagonists affect the neuronal activity of the NTS neurons, and 3) whether ET-1 or ET receptor antagonists modulate the responses of the nucleus of the solitary tract (NTS) neurons to l-glutamate (Glu). The single-unit discharge was extracellularly recorded with a fine electrode from medulla brain slice preparations of rats. ET-1 and Glu were iontophoretically applied to the recorded neuron. Both ET-1 and Glu increased the neuronal activity. The ETA receptor antagonist BQ-123 attenuated the basal neuronal activity. ET-1 augmented the magnitude of the increases in the neuronal activity evoked by Glu, and these responses were antagonized by BQ-123. These studies suggest the following conclusions: 1) ET-1 increases the neuronal activity of the NTS neurons via ETA receptors, 2) endogenous ET plays a controlling role of the neuronal activity of NTS neurons, and 3) ET-1 augments the responses evoked by Glu, believed to be the neurotransmitter from the solitary tract, via ETA receptors. These results suggest that ET-1 facilitates synaptic transmission in the NTS.

Abstract —It has been shown that nitric oxide in the brain stem plays an important role in the control of sympathetic nerve activity. We examined the role of endogenous nitric oxide in the brain stem in the rapid central adaptation of baroreflex control of sympathetic nerve activity in anesthetized rabbits. Bilateral carotid sinuses were isolated, and a stepwise increase in pressure of 25 or 50 mm Hg for 50 to 60 seconds was applied to the carotid sinuses while the arterial pressure and renal sympathetic nerve activity were recorded. The renal sympathetic nerve activity was inhibited by the stepwise increase in carotid sinus pressure, but thereafter it gradually returned toward the baseline level despite the fact that carotid sinus pressure was kept constant. This procedure was performed after intracisternal injection of N ω -nitro- l -arginine methyl ester (L-NAME, 8 μmol), N ω -nitro- d -arginine methyl ester (D-NAME, 8 μmol), l -arginine (40 μmol), or the vehicle solution. The magnitude of the immediate and maximal inhibition of renal sympathetic nerve activity caused by a stepwise increase in carotid sinus pressure was similar between the vehicle and L-NAME treatment, but the rate of recovery of the renal sympathetic nerve activity after immediate inhibition was faster after L-NAME than after vehicle. l -Arginine reversed the effects of L-NAME. However, D-NAME or l -arginine alone had no such effects on the rate of recovery of the nerve activity. These results thus suggest that endogenous nitric oxide in the brain stem attenuates rapid adaptation of the arterial baroreflex control of the sympathetic nerve activity in rabbits.

We report a case of a patient with vasovagal syncope, in whom isoproterenol infusion provoked vasovagal response without upright tilting. We subjected the patient, who had had two previous syncopal and several presyncopal episodes, to upright tilting with isoproterenol infusion. Before a control tilt was performed for 10 min (80 degrees), the patient was placed in the supine position for 5 min. The control tilt did not provoke a vasovagal response. With isoproterenol being infused at a dose of 1 mu g/min, the sequence of positioning in the supine position for 5 min and upright tilting for 10 min was repeated. This dose of isoproterenol infusion did not provoke any vasovagal response in the patient, either in the supine or in the upright position. When the dose of isoproterenol infusion was then increased to 2 mu g/min, the heart rate increased to 121/min, but then suddenly dropped to 74/min; systemic arterial pressure simultaneously fell from 148/80 to 108/80 mmHg. The patient complained of palpitation and anxiety, and showed profound cold sweating. The drop in the heart rate and the fall in blood pressure occurred when the patient was in the supine position, indicating that, unlike upright tilting with isoproterenol infusion, venous return was not decreased at the beginning of vasovagal response in this setting. This observation suggests that isoproterenol infusion, even without upright tilting, may provoke the vasovagal response in some patients.

Background The purpose of this study was to use a contemporary database to examine the relationship between annual hospital volume and the outcomes of percutaneous coronary interventions (PCIs) for acute myocardial infarction (AMI), given the wide spread use of coronary stents. An inverse relation exists between the number of PCIs and short-term outcome, but PCI practice has been changing with the availability of new devices such as stents. Methods and Results Data from the 1997 Japanese nationwide registry were analyzed to determine the relation between the annual hospital volume of PCI procedures for patients with AMI and in-hospital mortality, as well as the need for coronary artery bypass graft (CABG) surgery. A total of 129 hospitals (2,491 patients) were divided into terciles according to the annual volume. Of the procedures, 39% involved coronary stents. Median annual PCI volumes varied across terciles from low =10, middle =33, and high =89. After adjusting for patient characteristics, there was no significant relationship between volume and in-hospital mortality (trend P=0.66) and CABG (trend P=0.35). Among patients who received stents (n=958), there was no significant association between volume and either mortality or CABG. Conclusions Using the contemporary database, there was no significant relationship between hospital volume and in-hospital outcome among AMI patients undergoing PCIs. (Circ J 2004; 68: 887 - 891)

Randomized clinical trials have demonstrated that coronary stenting is more successful than balloon angioplasty in improving short- and long-term outcomes. However, it remains unknown whether those results can be generalized to broad-based practice. This study aimed to determine whether the outcome for patients with acute myocardial infarction (AMI) undergoing coronary stent placement would be better than those undergoing balloon angioplasty. The risk-adjusted mortality and subsequent revascularization rates were compared for 2185 patients from a nationwide Japanese registry during 1997. A total of 1349 patients were treated with balloon angioplasty alone and 836 had stent placement. There were no statistically significant differences in the prevalence of demographic, clinical, and angiographic variables, except that the angioplasty group had a greater proportion of female patients and those with a left circumflex lesion. Unadjusted in-hospital mortality was comparable (7.6 vs 6.3%; p=0.28), despite higher angiographic success rate for the stent group (89.7 vs 97.7%; p0.01). Adjusted odds ratio for in-hospital mortality was 0.75 (p=0.19). The same-admission bypass surgery rate was also similar. The 1.9-year post-discharge mortality rate was similar. The need for subsequent revascularization procedures was also similar, but restenosis was significantly lower in the stent group (34 vs 45%; p0.01). The superiority of clinical outcome for stenting rather than balloon angioplasty could not be demonstrated in broad-based registry patients, despite technically successful results.

Previous studies have identified risk factors for short- and long-term outcomes for patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). However, it remains unknown whether they can be generalized to current PCI practice for a broader cohort of patients. We analyzed the follow-up information (mortality and revascularization procedures) obtained from a nationwide Japanese registry during 1997 of a total of 2,211 patients with AMI who underwent PCI at 143 facilities. Demographic, clinical, angiographic, and procedural variables were submitted to statistical analysis to detect the risk factors of adverse outcomes. In-hospital and 1-year mortality rates were 7.1% and 10.9%, respectively. The most important risk factor for in-hospital death was attempted PCI of the left main (LM) coronary artery. Further independent risk factors for death were left ventricular (LV) dysfunction (ejection fraction

The Japanese Coronary Intervention Study (JCIS) has revealed that 17,667 coronary artery bypass grafting (CABG) procedures were performed at 477 facilities during 1997, and this report describes the demographic and clinical characteristics, treatment strategies, and the in-hospital and the long-term outcomes in patients treated with CABG in Japan. A total of 1,862 CABG cases, which corresponded to approximately 10% of the overall CABGs, were selected at random. The mean age was 65 years, and 76% of cases were males. The most prevalent clinical diagnosis was stable angina (54%), followed by myocardial infarction (MI) excluding acute myocardial infarction (AMI) (48%), unstable angina (25%), and AMI (5%). A large proportion of cases had multivessel coronary artery disease: 3-vessel disease (56%) and left main trunk disease (29%). The CABG procedures were emergency in 16%, and 93% of anastomotic sites were patent. In-hospital mortality and MI occurred in 5.1% and 3.5% of cases, respectively. The in-hospital mortality rate for emergency CABG was 12.0%, whereas that for elective CABG was 3.8%. The overall mortality rate during the follow-up period of 2.3 years was 10%. During the follow-up period, MI and angina occurred in 2% and 8% of cases, respectively. Percutaneous coronary intervention (PCI) was performed for 8%, and repeat CABG for 0.8%. In Japan, CABG was performed in patients with multivessel coronary artery disease with extensive risk factors. Angiographically determined success was achieved in 93% and the need for subsequent revascularization was relatively low.

Recent studies have suggested that the central nervous system is responsible for activation of sympathetic nerve activity (SNA) and the renin-angiotensin system in heart failure (HF). The aim of this study was to determine whether activation of the renin-angiotensin system within the nucleus of the solitary tract (NTS) plays a role in enhanced SNA in HF. High-output HF was induced by an aortocaval (A-V) shunt with some modifications in the rat. These rats exhibited a left ventricular dilatation and hemodynamic signs of high-output HF. Urinary catecholamine excretion and maximal renal SNA (RSNA) were greater in the A-V shunted rats than in the control rats. Microinjection of an angiotensin II type 1-receptor antagonist, CV11974, into the NTS was performed. The arterial pressure and RSNA were reduced by CV11974 to a greater degree in the A-V shunted rats than in the control rats. The expression of angiotensin-converting enzyme mRNA in the medulla was greater in the A-V shunted rats than in the control rats. These results suggest that activation of the renin-angiotensin system within the NTS contributes to an enhanced SNA in this model.

Nitric oxide (NO) in the nucleus tractus solitarii (NTS) plays an important role in regulating sympathetic nerve activity. The aims of this study were to determine whether the activation of N-methyl-d-aspartate (NMDA) receptors in the NTS facilitates the release ofl-glutamate (Glu) via NO production, and, if so, to determine whether this mechanism is involved in the depressor and bradycardic responses evoked by NMDA. We measured the production of NO in the NTS as NO[Formula: see text] and NO[Formula: see text](NOx) or Glu levels by in vivo microdialysis before, during, and after infusion of NMDA in anesthetized rats. We also examined effects of Nω-nitro-l-arginine methyl ester (l-NAME) on the changes in these levels. NMDA elicited depressor and bradycardic responses and increased the levels of NOxand Glu. l-NAME abolished the increases in the levels of NOxand Glu and attenuated cardiovascular responses evoked by NMDA. These results suggest that NMDA receptor activation in the NTS induces Glu release through NO synthesis and that Glu released via NO enhances depressor and bradycardic responses.

The pharmacological and physiological properties of excitatory amino acid and ACh systems in the nucleus of the solitary tract (NTS) were studied in slices of rat brain stem by extracellular and intracellular recordings from neurons activated by solitary tract (ST) stimulation. These neurons were characterized as having several long dendrites with multiple varicosities. Synaptic activation of the medial NTS (mNTS) neurons by ST stimulation was mediated by non-N-methyl-D-aspartate (NMDA) glutamate (Glu) receptors, because the excitation was blocked by 6-cyano-7-nitro-quinoxaline-2,3-dione but not by NMDA, nicotinic, or muscarinic antagonists. Identified mNTS neurons were excited by iontophoresis of both Glu and ACh. The most sensitive region of the cell was on the dendrites approximately 100 micrometer from the cell body for both putative neurotransmitters. Nicotinic and/or muscarinic excitatory ACh responses were detected on the mNTS neurons. Our observations suggest that both types of ACh receptors may contribute to the attenuation of the baroreceptor reflex, but the functional correlation of this receptor profile remains to be determined.