Effects of short-term fasting on the Akt-mediated pathway involved in protein metabolism in chicken skeletal muscle.

In the present study, we show that short-term (4 h) fasting significantly decreased the levels of protein synthesis-related factors such as the plasma insulin concentration, skeletal muscle pAkt, and pS6 levels in 2-wk-old chickens (P < 0.05). An intravenous injection of insulin significantly elevated the contents of pAkt and p-S6 in the skeletal muscle (P < 0.01). These findings suggest that decreasing the plasma insulin causes the downregulation of the Akt/S6 pathway in chicken skeletal muscle under short-term fasting conditions. However, protein synthesis was not significantly affected by short-term fasting. In addition, no significant change was observed in the levels of proteolysis-related factors such as plasma Nτ-methylhistidine, phosphorylated forkhead box class O, and muscle ring finger-1 during 4-h fasting, indicating that short-term fasting does not induce skeletal muscle proteolysis in chickens. Interestingly, atrogin-1 expression significantly increased after 2-h fasting (P < 0.05), and insulin injection significantly reversed the fasting-induced atrogin-1 expression in chicken skeletal muscle (P < 0.01). Collectively, these findings suggest that short-term fasting downregulates the insulin-stimulated Akt/S6 pathway but does not significantly affect protein synthesis and proteolysis in chicken skeletal muscle, and that atrogin-1 expression is upregulated in a FOXO1-independent manners.

Impact of antihypertensive medication adherence on blood pressure control in hypertension: the COMFORT study.

BACKGROUND: It has not been fully elucidated whether antihypertensive medication adherence affects blood pressure (BP) control in hypertension cases. AIM: To investigate the association of adherence to antihypertensive drug regimens and BP control using data from the Combination Pill of Losartan Potassium and Hydrochlorothiazide for Improvement of Medication Compliance Trial (COMFORT) study. DESIGN: An observational analysis from a randomized controlled trial. METHODS: A total of 203 hypertensive subjects were randomly assigned to a daily regimen of a combination pill (losartan 50 mg/hydrochlorothiazide 12.5 mg) or two pills, an angiotensin II receptor blocker and a thiazide diuretic. Medication adherence calculated based on pill counts and BPs was evaluated at 1, 3 and 6 months after randomization. RESULTS: The subjects were divided into three groups according to their adherence, i.e. relatively low-adherence (<90%; n = 19), moderate-adherence (90-99%; n = 71) and high-adherence (100%; n = 113) groups. Clinical characteristics of the subjects including BP, sex, randomized treatments and past medical history did not differ significantly among the three groups. Achieved follow-up BPs over the 6-month treatment period, which were adjusted for age, sex, baseline BP and randomized treatment, were significantly higher in the low-adherence group (135/78 mmHg) compared with the high-adherence (130/74 mmHg; P = 0.02/0.02) and the moderate-adherence (128/74 mmHg; P = 0.003/0.02) groups. CONCLUSION: Low adherence to an antihypertensive-drug regimen was associated with poor BP control.

B-type natriuretic peptide levels are decreased by reducing dietary salt intake in patients with compensated heart failure with preserved ejection fraction.

BACKGROUND: Dietary salt restriction is believed to be a mainstay in the management of patients with heart failure. However, the effect of salt intake on heart failure has not been well evaluated in outpatient medical practice. AIMS: The aim of the present study was to assess the hypothesis that B-type natriuretic peptide (BNP) level, as an objective marker of heart failure, is associated with salt intake in patients with heart failure. METHODS: One hundred and thirteen consecutive patients with mild compensated heart failure (77 ± 10 years old, 51 female) were included. We estimated dietary salt intake by the concentration of sodium and creatinine in spot urine. We measured BNP at the time of urine sampling and assessed the relationship between the % changes in BNP levels (%ΔBNP) and the changes in the estimated daily salt excretion (ΔNaCl) during the follow-up period. RESULTS: The baseline median BNP level was 150 (interquartile range: 83-263) pg/mL and the estimated daily salt excretion was 162 ± 45 mmol/day. There was a positive correlation between %ΔBNP and ΔNaCl (r = 0.61, P < 0.01). Multiple regression analysis revealed that %ΔBNP was associated with ΔNaCl (P < 0.01), but not with changes in systolic blood pressure and bodyweight. CONCLUSIONS: Changes in BNP levels were associated with changes in the estimated daily salt excretion in outpatients with compensated heart failure. Salt restriction may be beneficial for the management of patients with heart failure.

The Phase III, double-blind, parallel-group controlled study of amlodipine 10 mg once daily in Japanese patients with essential hypertension who insufficiently responded to amlodipine 5 mg once daily.

The objective of this Phase III double-blind parallel-group controlled study was to examine the superiority of amlodipine 10 mg once daily (the amlodipine 10 mg group) to amlodipine 5 mg once daily (the amlodipine 5 mg group) in 305 Japanese outpatients with essential hypertension whose systolic blood pressure (SBP) had not reached the therapeutic target levels (<130-140/80-90 mm Hg) when treated with amlodipine 5 mg once daily. This study consisted of the 1-week prescreening, 8-week screening and 8-week double-blind periods. Changes in trough SBP from baseline at week 8 of the double-blind period (week 8) were -7.0 mm Hg and -13.7 mm Hg in the amlodipine 5 and 10 mg groups, respectively; a significant difference (P<0.001) was found between the two groups. Changes in trough diastolic blood pressure (DBP) from baseline at week 8 were -2.7 mm Hg and -6.8 mm Hg in the amlodipine 5 and 10 mg groups, respectively, with a significant difference (P<0.001) between the two groups. At week 8, responder rates were 28.5 and 44.0% in the amlodipine 5 mg and 10 mg groups, respectively, with a significant difference (P=0.002) between the two groups. The amlodipine 10 mg group showed no significant difference in the incidences of adverse events against the amlodipine 5 mg group. The incidence of mild peripheral oedema was 4% only in the amlodipine 10 mg group. In conclusion, amlodipine 10 mg once daily was found to be superior to amlodipine 5 mg once daily, safe, well tolerated and useful for the relevant subjects.

Low-dose prednisolone ameliorates acute renal failure caused by cholesterol crystal embolism.

AIMS: The prognosis of renal cholesterol crystal embolism (CCE) is poor. Although various treatments for CCE have been attempted, there is no optimal therapy. We tested the effect of low-dose prednisolone (PS) on CCE-related acute renal failure (ARF). PATIENTS AND METHODS: 7 patients (mean age 69 years) diagnosed with CCE-related ARF were treated with oral PS at 15-20 mg/day for 2-4 weeks, which was then tapered at 5 mg/day over 2-4 weeks, followed by 5 mg/day maintenance dose. Recurrent ARF during PS tapering was treated with a larger dose of PS. RESULTS: Inciting factors were identified in four patients: coronary angiography (n=3) and cerebral angiography (n=1). On admission, serum creatinine (SCr) was 2.1 +/- 0.3 mg/dl (mean +/- SEM). SCr and eosinophil count before treatment were 4.2 +/- 0.4 mg/dl and 682 +/- 73/microl, respectively. PS therapy improved ARF in all cases at week 2 (SCr 3.8 +/- 0.5 mg/dl) parallel to a decrease in eosinophilia (116 +/- 30/microl), and at week 4 (3.1 +/- 0.4 mg/dl and 134 +/- 20/microl, respectively). At last follow-up, renal function was improved or maintained in 5 patients compared with that at week 4 post-treatment. One patient died of lung cancer. Another required LDL apheresis and hemodialysis but died due to CCE-related multi-organ failure. A third patient had recurrent ARF and was re-treated with a larger dose of PS, which resulted in an immediate decrease in SCr. However, the patient developed acute renal dysfunction due to congestive heart failure, and required hemodialysis. CONCLUSIONS: Low-dose PS improved CCE-related ARF, probably through amelioration of inflammatory reaction surrounding affected renal vessels.

Coronary risk factors in Kawasaki disease treated with additional gammaglobulin.

AIMS: To assess the hypothesis that an additional intravenous gammaglobulin (IVGG) infusion, if administered early, may prevent coronary artery lesions (CAL) in patients with Kawasaki disease (KD) who do not respond to initial IVGG therapy. METHODS: Forty four KD patients (17 with CAL and 27 without CAL), treated with additional IVGG because of persistent or recrudescent fever after initial IVGG therapy, were studied. Main outcome measures were the presence of CAL by echocardiography and the number of febrile days before and after start of additional IVGG infusion (pre- and post-additional IVGG). RESULTS: In univariate analyses, risk factors for CAL were the number of febrile days pre-additional IVGG, the number of febrile days post-additional IVGG, the number of days that initial IVGG was divided over, the white blood cell count pre- and post-additional IVGG, and the C reactive protein concentration pre-additional IVGG. In a multivariate analysis, the only independent risk factor was the number of febrile days pre-additional IVGG (> or =10 days; odds ratio 7.86; 95% CI 1.44 to 42.8; p = 0.02). CONCLUSIONS: Among KD patients with persistent or recrudescent fever after initial IVGG therapy, administration of additional IVGG before the first 10 febrile days was associated with a decreased prevalence of CAL, when compared with the prevalence in those who were retreated later. An additional IVGG infusion, if administered early, may prevent CAL in initial IVGG non-responders.

Improvement of blood pressure control in a hypertension clinic: a 10-year follow-up study.

The objective of the study was to assess whether the publication of new guidelines, such as JNC VI 1997 and WHO/ISH 1999, and the development of new antihypertensive drugs have improved blood pressure (BP) control. A total of 150 patients (age 29-88, mean 66+/-11 years in 2001) who were followed at our hypertension clinic during 1991-2001 were retrospectively investigated. We compared the clinical characteristics of the patients in 2001 to those in 1991 and 1996, using the averaged BP determined at two occasions each year for our analysis. The average BP decreased during the 10 years between 1991 and 2001. When good BP control was defined as <140/90 mmHg, the rate of patients with good BP control increased from 31% in 1991 to 43% in 1996, and to 57% in 2001 (P<0.001 vs 1991). Both younger (< or =64 years) and older (> or =65 years) patients showed similar improvement during these 10 years. In 2001, satisfactory BP control (<130/85 mmHg) was achieved in 24% of younger patients, which was significantly higher than the achievement in 1991 (10%, P=0.02). This improvement occurred at the same time as an increase in the prescription of Ca antagonists and angiotensin II antagonist. The patients with improved BP control during these 10 years (n=50) showed lower body mass index (BMI) and serum total cholesterol levels in 2001 compared to persistently uncontrolled patients (n=54). Furthermore, the change in BMI during these 10 years was significantly less in the patients with improved BP control than in the persistently uncontrolled patients. In conclusion, BP control improved in the 10 years studied, and it seems to be attributable to the more frequent use of the newer drugs such as angiotensin II antagonists and Ca antagonists, to lifestyle modification and also to the growth in awareness of the importance of strict BP control.

Magnesium decreases arterial pressure and inhibits cardiovascular responses induced by N-methyl-D-aspartate and metabotropic glutamate receptors stimulation in rostral ventrolateral medulla.

OBJECTIVE: Magnesium sulfate (MgSO4) is widely used for the treatment of eclampsia. However, effects of Mg2+ in central cardiovascular regulation remain unclear. In the present study, the role of Mg2+ on cardiovascular regulation in the rostral ventrolateral medulla (RVLM) of rats was examined. METHODS: Adult male Wistar rats were anesthetized with urethane, and artificially ventilated. The ventral surface of the medulla was exposed, and the RVLM was identified by microinjection (50 nl) of l-glutamate (l-Glu; 2 nmol). Then, MgSO4 (1, 3, 10 nmol, n = 7 for each dose) and magnesium chloride (MgCl2; 10 nmol, n = 7) were microinjected into the RVLM. l-Glu (2 nmol), N-methyl-D-aspartate (NMDA; 20 pmol), alpha-amino-3-hydroxy-5-methyl isoxazole-4-propionic acid (AMPA; 5 pmol) and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD, metabotropic glutamate receptor agonist; 1 nmol] were also microinjected with or without pretreatment of MgSO4 (10 nmol; n = 7 for each drug). RESULTS: MgSO4 dose-dependently decreased mean arterial pressure (MAP) and heart rate (HR). The high dose of MgSO4 (10 nmol) significantly decreased MAP and HR (-25 +/- 4 mmHg and -43 +/- 6 bpm). Similarly, MgCl2 decreased MAP and HR (-27 +/- 4 mmHg and -30 +/- 6 bpm). The pressor response evoked by NMDA or (1S,3R)-ACPD was significantly attenuated by the pretreatment with MgSO4. In contrast, pressor response caused by l-Glu or AMPA was not affected by pretreatment with MgSO4. CONCLUSIONS: These results suggest that Mg2+ has an inhibitory role on the RVLM neurons, and inhibits cardiovascular responses induced by NMDA and metabotropic glutamate receptor agonists.

Central human cocaine- and amphetamine-regulated transcript peptide 55-102 increases arterial pressure in conscious rabbits.

We determined cardiovascular and neurohormonal responses to intracerebroventricular administration of human cocaine- and amphetamine-regulated transcript (CART) peptide 55-102 in conscious rabbits. Intracerebroventricular injection of CART 55-102 elicited dose-related increases in mean arterial pressure and renal sympathetic nerve activity. Peak values of mean arterial pressure and renal sympathetic nerve activity induced by intracerebroventricular injection of 1 nmol of CART 55-102 (+5.0+/-2.6 mm Hg and +72.5+/-20.8%) were obtained 40 and 60 minutes after injection, respectively. Plasma epinephrine and glucose concentrations significantly increased 30 and 60 minutes after intracerebroventricular injection of CART 55-102 (control versus 60 minutes for epinephrine, 77.0+/-62.4 versus 1067.5+/-329.3 pg/mL, P<0.01; for glucose, 6.25+/-0.33 versus 11.57+/-0.93 mmol/L, P<0.01). Plasma norepinephrine concentrations also significantly increased at 30 minutes. Plasma insulin, vasopressin, and cortisol concentrations increased at 60 minutes but did not attain significant values. However, pretreatment with intravenous injection of pentolinium (5 mg/kg), a ganglion-blocking agent, eliminated these cardiovascular and neurohormonal responses. In contrast, intravenous injection of the same dosage of CART 55-102 (1 nmol) as that used in the intracerebroventricular experiment failed to cause any cardiovascular and renal sympathetic nerve responses. These results suggest that intracerebroventricular human CART 55-102 acts in the central nervous system and activates sympathoadrenal outflow, which results in increases in arterial pressure and plasma glucose levels in conscious rabbits.

Trends in the pathophysiological characteristics of malignant hypertension.

The aim of the present study is to investigate the pathophysiological characteristics of a number of recent cases of malignant hypertension (MHT) and to compare them to the characteristics of earlier cases. Patients with MHT (age 25-76, mean 44+/-2 years) who were admitted to our hospital from 1984-1999 were retrospectively studied. All of the patients had either grade III or IV retinopathy and diastolic blood pressure levels higher than 120 mmHg. The observations in this study were compared to previously reported findings regarding 59 MHT patients who were admitted from 1971-1983. Of the 37 recent MHT patients, 20 had essential hypertension (EHT) as the underlying disease, 13 had chronic glomerulonephritis (CGN), and the remaining 4 presented with other diseases including pyelonephritis and renovascular hypertension. A positive family history of hypertension was more prevalent in the EHT patients than in other patients, and persistent proteinuria, microhematuria, and anemia were more prevalent in the CGN patients. These characteristics were similar between the recent and previous cases. Within 4 weeks after admission, hemodialysis was initiated in 3 of the 13 patients (23%) with CGN and 2 of the 20 (10%) patients with EHT. The prevalence of renal death at 1 year after admission was 30%, which was lower than the prevalence in the previous cases (42%). Grade IV retinopathy was seen in 45% of the patients admitted from 1984-1999, significantly less than in the patients admitted from 1971-1983 (66%, p<0.05). In addition, left ventricular hypertrophy was less frequently observed on electrocardiogram in the recent cases (67%) than in the previous cases (88%, p<0.05). Our results suggest that the recent cases of MHT demonstrate less severe organ damage.

Central orexin-A augments sympathoadrenal outflow in conscious rabbits.

We determined the cardiovascular and neurohormonal responses to intracerebroventricular administration of orexin-A in conscious rabbits. Intracerebroventricular injection of orexin-A elicited dose-related increases in mean arterial pressure and renal sympathetic nerve activity. Peak values of mean arterial pressure and renal sympathetic nerve activity induced by intracerebroventricular injection of 100 pmol of orexin-A (14.0+/-0.7 mm Hg and 55.4+/-14.9%, respectively) were obtained at 40 and 25 minutes after injection, respectively. Plasma epinephrine and glucose concentrations were significantly increased at 60 and 90 minutes after intracerebroventricular injection of orexin-A (control versus 90 minutes; for epinephrine, 38.0+/-12.8 versus 167.5+/-42.5 pg/mL, P<0.01; for glucose, 6.66+/-0.18 versus 7.75+/-0.14 mmol/L, P<0.01). Plasma norepinephrine and insulin concentrations increased at 60 and 90 minutes but did not attain significant values. Intracerebroventricular injection of orexin-A also caused significant increases in plasma vasopressin concentrations. However, pretreatment with an intravenous injection of pentolinium (5 mg/kg), a ganglion-blocking agent, abolished these cardiovascular and neurohormonal responses. On the other hand, intravenous injection of the same dose of orexin-A (100 pmol) used in the intracerebroventricular experiment failed to cause any cardiovascular and renal sympathetic nerve responses. These results suggest that intracerebroventricular orexin-A acts in the central nervous system and activates sympathoadrenal outflow, resulting in increases in arterial pressure and plasma glucose levels in conscious rabbits.

The influence of chronic antihypertensive treatment on the central pressor response in SHR.

UNLABELLED: We examined the influence of chronic antihypertensive treatment on the central pressor response in SHR. Adult male SHR were divided into 5 groups, i.e., those receiving 1) enalapril (Enal: 25 mg/kg/day in drinking water, n=12); 2) losartan (Los: 40 mg/kg/day, n=11); 3) candesartan (Cand: 4 mg/kg/day, n=12); 4) hydralazine+hydrochlorothiazide (H&H: 50+7.5 mg/kg/day, n=9); 5) vehicle ( CONTROL: n=9). At 4 weeks of treatment, hypertonic saline (0.25, 0.5 M) was intracerebroventricularly (i.c.v.) injected into conscious rats. Plasma catecholamines were measured before and after i.c.v. injection. On completion of the experiment, heart weight was measured, and angiotensin-converting enzyme (ACE) activity of the cerebrum was determined. All antihypertensive drugs elicited comparable reductions in systolic blood pressure, while heart rate was significantly higher in the H&H group than in the other groups during treatment. Pressor response to i.c.v. hypertonic saline (0.5 M) was significantly smaller in the Enal (12 +/- 3 mmHg) and Cand (11 +/- 2 mmHg) groups than in the Los (22 +/- 2 mmHg), H&H (16 +/- 2 mmHg), and CONTROL (29 +/- 5 mmHg) groups. Plasma catecholamines did not differ among the groups. Heart weight was lowest in the Enal group, followed by the Los and Cand groups. ACE activity of the cerebrum was significantly decreased in the Enal group. The results suggest that chronic treatment with various antihypertensive drugs differentially alters the central pressor response in SHR, and enalapril and candesartan are effective in attenuating this response.

Altered diurnal variation of blood pressure in elderly subjects with decreased activity of daily living and impaired cognitive function.

Activity of daily living (ADL) and cognitive are indices of physical and psychological activity in elderly subjects. The present study was performed to clarify the relationship among ADL, cognitive function, and ambulatory blood pressure (ABP) in the elderly. Study subjects were 77 females and 22 males (aged 60 to 101 years) with various levels of ADL and cognition, who were in nursing homes or geriatric hospitals. ABP was recorded every 30 min for 24 h by a noninvasive device. Mini-mental state examination (MMSE) and Barthel index measurement were used to evaluate cognitive function and ADL, respectively. Both the MMSE and Barthel index values showed a significant positive correlation with daytime ABP but not with nighttime ABP. The dip in nighttime BP correlated negatively with age, and positively with MMSE and Barthel index. In the multiple regression analysis, age and Barthel index values remained significant determinants of the dip in nighttime BP. Presence of stroke and MMSE became significant when the Barthel index values were removed from the analyses. When subjects were classified by tertiles of MMSE or Barthel index, subjects in the lowest MMSE group and those in the lowest Barthel index group had both lower daytime ABP and smaller nighttime BP dip than those of the other groups. A low BP level during the daytime was associated with altered diurnal variation of BP in elderly subjects with greater age, impaired cognitive function, and/or decreased ADL. ADL had a greater influence on diurnal BP variation than did cognitive function.

A case of erythropoietic protoporphyria with liver cirrhosis suggesting a therapeutic value of supplementation with alpha-tocopherol.

Erythropoietic protoporphyria (EPP) was diagnosed in a 27-year-old man based on a typical clinical history, and a marked increase in erythrocyte and fecal protoporphyrin concentrations. Although liver disease is not a common feature in EPP, he had slight liver dysfunction. A percutaneous liver biopsy was performed and it showed minimal hepatocellular damage and many reddish brown pigment deposits in hepatocytes, Kupffer cells, portal histiocytes, bile canaliculi and small biliary radicles. Electron microscopic findings confirmed that these deposits were composed of protoporphyrin crystals. Liver biochemistry remained well for >2 years, but deteriorated rapidly and second liver biopsy obtained 28 months after the first biopsy revealed the development of liver cirrhosis. We treated the patient with intravenous administration of dl-a-tocopherol acetate (vitamin E; 500 IU/body/day). Following the administration of vitamin E, the concentration of protoporphyrin in erythrocytes decreased significantly and the liver function tests were improved. Sixteen weeks later he showed the full clinical and biochemical recovery suggesting that vitamin E supplementation might be useful in treating patients with EPP who developed liver damage.

Central infusion of L-arginine or superoxide dismutase does not alter arterial pressure in SHR.

Cardiovascular responses to L-arginine and nitric oxide (NO) are augmented in the rostral ventrolateral medulla (RVLM) of spontaneously hypertensive rats (SHR), and the intravenous injection of superoxide dismutase (SOD) mimetic decreases the arterial pressure in these rats. In the present study, we examined whether the chronic central infusion of L-arginine or an SOD mimetic would reduce the blood pressure of SHR and alter responses to an NOS inhibitor or an NO donor in the RVLM. For this purpose, we administered L-arginine (SHR-Arg: 13.2 micromol/day, n=6), a stable membrane-permeable SOD mimetic, 4-hydroxy-2, 2,6,6-tetramethyl piperidine-1-oxyl (tempol) (SHR-Temp: 13.2 micromol/day, n=6), or vehicle (SHR-C: n=6) into the lateral ventricle of 12-week-old SHR for 2 weeks. When the rats reached 14 weeks of age, N(G)-nitro-L-arginine methyl ester (L-NAME: 10 nmol/50 nl) or NOC 18 (NO donor: 10 nmol/50 nl) was microinjected into the unilateral RVLM. Blood pressure did not decrease in any of the treatment groups (SHR-Arg: 209+/-4 mmHg, SHR-Temp: 210+/-6 mmHg, SHR-C: 197+/-6 mmHg). The microinjection of L-NAME into the RVLM induced a significant increase in the mean arterial pressure (MAP) (SHR-Arg: 10-4 mmHg, SHR-Temp: 12+/-4 mmHg, SHR-C: 11+/-3 mmHg), and the increases in MAP did not differ among the groups. The micro-injection of NOC 18 reduced MAP (SHR-Arg: -12+/-2 mmHg, SHR-Temp: -15+/-3 mmHg, SHR-C: -13+/-3 mmHg), and the depressor responses were comparable among groups. These results do not support the hypothesis that chronic L-arginine deficiency or the enhanced degeneration of NO by superoxide radicals in the central nervous system contributes to the maintenance of arterial pressure in SHR.

Cardiovascular responses to glutamate and angiotensin II in ventrolateral medulla of hypertension induced by chronic inhibition of nitric oxide.

It has been suggested that nitric oxide (NO) influences the actions of L-glutamate and angiotensin II in the brain. In the present study, we examined whether cardiovascular responses to L-glutamate and angiotensin II would be altered in the rostral ventrolateral medulla (RVLM) of rats treated with an NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). Wistar rats were treated with either L-NAME (100 mg/kg/day, n=9) or vehicle (n=8) for 4 weeks. L-glutamate (2 nmol/50 nl) or angiotensin 11 (100 pmol) was then microinjected into unilateral RVLM of anesthetized rats. Upon completion of the experiments, angiotensin-converting enzyme (ACE) activity of the brain stem was measured. The systolic blood pressure after 4 weeks of the treatment was significantly higher in the L-NAME group (203+/-8 mmHg) than in the control group (142+/-3 mmHg, p< 0.01). The pressor response to L-glutamate microinjected into the RVLM was significantly greater in the L-NAME group (31+/-2 mmHg) than in the control group (24+/-1 mmHg, p< 0.01). Similarly, angiotensin II showed a greater pressor response in the L-NAME group. ACE activity of the brain stem did not differ between the groups. In conclusion, NO may have an inhibitory influence on the actions of L-glutamate and angiotensin II in the RVLM.

Metabotropic glutamate receptor subtypes involved in cardiovascular regulation in the rostral ventrolateral medulla of rats.

We have previously reported that metabotropic glutamate receptors (mGluR) participate in cardiovascular regulation in the rostral ventrolateral medulla (RVLM) of rats. In the present study, we have tried to elucidate which subtype of mGluR contributes to cardiovascular responses elicited by L-glutamate in the RVLM. Adult male Wistar rats (348 +/- 11 g, n = 21) were anesthetized and artificially ventilated. Microinjections of agonists and antagonists for each mGluR subtype were done into unilateral RVLM. Each of group I, II and III mGluR agonist (1 nmol/50 nl) produced significant increases in arterial pressure (18 +/- 2, 9 +/- 2 and 34 +/- 3 mmHg, respectively) and heart rate (18 +/- 4, 13 +/- 3 and 33 +/- 12 bpm, respectively). Microinjections of group I, II and III mGluR antagonists failed to inhibit the cardiovascular responses induced by subsequently injected agonists. However, group I antagonist [(RS)-1-aminoindan-1,5-dicarboxylic acid] elicited transient increases in arterial pressure and heart rate, followed by decreases in both variables (-19 +/- 4 mmHg and -22 +/- 4 bpm). These results suggest that all of three subtypes of mGluR participate in cardiovascular responses induced by L-glutamate, and group I mGluR may play an important role in the maintenance of arterial pressure.