Urinary Norepinephrine Excretion Research Articles

Depression and anxiety symptoms are related to increased 24-hour urinary norepinephrine excretion among healthy middle-aged women

Objective Depression is a risk factor for morbidity and mortality in a variety of populations, and anxiety has also been associated with risk of mortality among cardiac patients. Dysfunction of the autonomic nervous system may be involved in this risk. The primary goal of this study was to evaluate the relationship between levels of self-reported symptoms of depression and anxiety and 24-hour urinary catecholamine excretion. Method Ninety-one women aged 47–55 years were evaluated. Depression symptoms were assessed with the Beck Depression Inventory (BDI) and state anxiety was assessed with the state anxiety portion (SAI) of the Spielberger State–Trait Anxiety Inventory (STAI). Twenty-four hour urine collections were assayed for epinephrine (EPI), norepinephrine (NE) and cortisol (CORT). EPI, NE and CORT were indexed by body surface area to control for individual differences in body size. Results Higher levels of depression symptoms were associated with increased 24-hour NE excretion ( r=.27, P=.009), with depressed women ( n=17, BDI scores ≥10) exhibiting an approximately 25% higher rate of urinary NE excretion than women with BDI scores <10 ( n=74), P=.007. Higher levels of state anxiety were also related to greater NE excretion ( r=.28, P=.01), and CORT excretion was related to both depression ( r=.23, P=.02) and anxiety ( r=.22, P=.04). Depression and anxiety symptoms were unrelated to urinary EPI excretion. Conclusions The current findings that higher levels of depression and anxiety symptoms are related to increased 24-hour urinary NE and CORT excretion among women suggests that depression and anxiety may be associated with increased sympathetic nervous system (SNS) activity, and are consistent with the possibility that SNS activity may play a role in the increased mortality associated with depression in community-dwelling older adults.

Depression and anxiety symptoms are related to increased 24-hour urinary norepinephrine excretion among healthy middle-aged women

Depression and anxiety symptoms are related to increased 24-hour urinary norepinephrine excretion among healthy middle-aged women

Effects of acute hypercholesterolemia on blood pressure and pressor response to norepinephrine in rats

To examine if high cholesterol in blood acutely affects the blood pressure, we partly exchanged the blood of normal rats for that of hypercholesterolemic rats. Male Sprague–Dawley rats were fed for 8 weeks with a high‐cholesterol diet (4% cholesterol; HC) or a normal diet (NC). The rats were catheterized, and blood of animals in NC was partly exchanged with that of HC (N‐H) or other animals in NC (N‐N). Systolic blood pressure (SBP) and the pressor response to norepinephrine (NE) in N‐H were compared with those of N‐N. Serum lipids and malondialdehyde (MDA), and urinary excretion of protein (UP) and NE (UNE) were determined. After 8 weeks, SBP, serum total cholesterol (TC), MDA, UP and UNE were higher in the HC. Blood exchange caused an increase in TC, MDA and SBP in only the N‐H. Increases in SBP caused by NE injection were rather less in the N‐H than in the N‐N. The blood pressure increase induced by a high‐cholesterol diet seemed to be caused by certain factors in the blood of hypercholesterolemic rats. Excessive lipid oxidation induced by hypercholesterolemia may be involved in the blood pressure elevation.

Effects of barefoot habituation in winter on thermal and hormonal responses in young children--a preliminary study.

This study investigated how socks-wearing habit or habitual barefoot in the cold winter affected skin temperatures of distal lower extremities, the urinary excretion of adrenaline, noradrenaline and cortsisol in young children. In Experiment I for preschool children, the measurements of foot and leg skin temperatures were conducted for 30 min in the classroom controlled at 23+/-2 degres C and 50+/-5%RH, and the excretion of urinary catecholamines and cortisol during nocturnal sleep were analyzed. In Experiment II for elementary school children, nocturnal secretion of urinary catecholamines and cortisol was analyzed. While leg skin temperature tended to be lower in barefoot group than in socks group during Experiment I, foot skin temperature was not significantly different between the two groups. Fall of leg skin temperature during 30 min measurement tended to be smaller in barefoot group than in socks group. Urine volume and urinary excretion of cortisol tended to be greater in barefoot group than in socks group for preschool children. Urinary noradrenaline was significantly greater and cortisol tended to be greater in barefoot group than in socks group for elementary school children. Considering that most of the findings shown above were in the proximity of the established level of statistical significance, it was provisionally concluded that young children with barefoot habituation might show more effective cold adaptation of metabolic type than those without the habituation do, by keeping their skin temperatures higher even in the cold and enhancing the metabolic rate.

The Effect of Successful Heart Transplant Treatment of Heart Failure on Central Sleep Apnea

Central sleep apnea (CSA) associated with Cheyne-Stokes respiration in patients with congestive heart failure (CHF) is thought to be an acquired pattern of respiratory control instability related, at least in part, to elevated sympathetic nervous system activity. The effect of restoring heart function to normal with heart transplantation in patients with CHF and CSA has only been reported within weeks of the transplant and with varying results. The purpose of the study was to evaluate the impact of successful heart transplant on sympathetic nervous system activity and CSA severity in patients with CHF. Controlled prospective trial. University hospital. Twenty-two patients with CHF (13 patients with CSA, and 9 patients with no sleep-disordered breathing [SDB]). Polysomnography, left ventricular ejection fraction (LVEF), and overnight urinary norepinephrine excretion (UNE) were measured before and > 6 months after successful heart transplantation. In the CSA group, there was a fall in apnea-hypopnea index (AHI) [mean +/- SD, 28 +/- 15 to 7 +/- 6/h; p < 0.001] and UNE (48.1 +/- 30.9 to 6.1 +/- 4.8 nmol/mmol creatinine, p < 0.001) associated with normalization of LVEF (19.2 +/- 9.3% to 53.7 +/- 6.1%, p < 0.001) at 13.2 +/- 8.3 months following heart transplantation. Of the CSA group following transplantation, seven patients had no SDB (AHI < 5/h), three patients had persistent CSA (AHI, 12.3 +/- 0.9/h) and four patients acquired obstructive sleep apnea (OSA) [AHI, 11.2 +/- 7.4/h]. In comparison, none of the control group acquired CSA or OSA after transplantation. We conclude that CSA may persist despite normalization of heart function and sympathetic nerve activity.

Influence of α-adrenergic blockade on the catecholamine response to exercise at 4,300 meters

This investigation examined the influence of α-adrenergic blockade on plasma and urinary catecholamine responses to both exercise and high-altitude exposure. Sixteen nonsmoking, eumenorrheic women (age 23.2 ± 1.4 years, 68.7 ± 1.0 kg) were studied at sea level and during 12 days of high-altitude exposure (4,300 m). Subjects received either α-blockade (prazosin 3 mg/d) or a placebo in a double-blinded, randomized fashion. Resting plasma and 24-hour urine samples were collected periodically throughout the duration of the study. Further, subjects participated in submaximal exercise tests (50 minutes at 50% sea level maximum oxygen consumption [Vo2max]) at Sea level and on days 1 and 12 at altitude. Urinary norepinephrine (NE) excretion rates increased significantly over time at altitude, with blocked subjects having greater values compared to controls. Plasma NE levels increased significantly with chronic altitude exposure compared to sea level and acute hypoxia both at rest and during exercise. NE levels at rest were greater for blocked compared to control subjects during all conditions. Urinary and plasma epinephrine (EPI) levels increased dramatically, with acute altitude exposure returning to sea level values by day 12 of altitude exposure. EPI levels were greater for blocked compared to placebo both at rest and during exercise for all conditions studied. Changes in α-adrenergic activity over time at altitude were associated with select metabolic and physiologic adjustments. The presence of α-blockade significantly affected these responses during chronic altitude exposure. It was concluded that: (1) α- adrenergic blockade elicited a potentiated sympathoadrenal response to the stress of both exercise as well as high-altitude exposure, and (2) the sympathetics, via α-adrenergic stimulation, contribute to a number of key adaptations associated with acclimatization to high altitude.

Comparison of the effects of losartan and angiotensin converting enzyme inhibitor on nocturnal blood pressure in patients with stroke

Background: Therapy of nocturnal hypertension was shown to be beneficial for primary and secondary prevention of stroke. We investigated the effects of angiotensin II antagonist (losartan) and angiotensin converting enzyme (ACE) inhibitor (quinapril) on nocturnal blood pressure and sympathetic nervous activity in patients with hypertension and stroke. Methods: According to a prospective, randomized, crossover design, 30 hypertensive patients with a previous history of stroke were assigned randomly to receive losartan (50 mg) or quinapril (10 mg) once daily for 4 weeks. The patients were switched to the alternative regime for an additional 4-week period. In the last week of each treatment, 24-h ambulatory blood pressure (BP) monitoring was performed every 30 min, and 24-h urine was collected for the measurement of catecholamine. Results: Neither systolic nor diastolic BPs during daytime differed between losartan and quinapril treatments, but those during nighttime were lower under losartan treatment than under quinapril treatment. The nocturnal decreases in systolic and diastolic BPs were both greater under losartan treatment than under quinapril treatment. The nocturnal decrease in urinary norepinephrine (NE) excretion was greater under losartan treatment than under quinapril treatment. Conclusions: Losartan augments the nocturnal decrease in ambulatory BP compared with that of quinapril in patients with a previous history of stroke, presumably via the suppression of nocturnal sympathetic nervous activity.

Duloxetine Increases Serotonin and Norepinephrine Availability in Healthy Subjects: A Double-Blind, Controlled Study

Evidence suggests that compounds that increase the synaptic availability of more than one neurotransmitter have greater efficacy in the treatment of depression than single-acting drugs. Preclinical studies indicate that duloxetine acts to inhibit serotonin (5-HT) and norepinephrine (NE) transporters. The ability of duloxetine to alter 5-HT and NE reuptake was tested in 12 healthy male subjects. Placebo, desipramine 50 mg b.i.d., and duloxetine (80 mg q.d. or 60 mg b.i.d.) were compared in a randomized, double-blind, three-period crossover study in 12 healthy male subjects. Whole-blood 5-HT, urinary excretion of NE and major metabolites, and TYR PD30 (IV tyramine pressor dose needed to increase systolic blood pressure by 30 mmHg) were measured at steady state. Vital signs were measured periodically. Duloxetine affected 5-HT reuptake, with whole-blood 5-HT depletion vs placebo (80 mg q.d.: p=0.07; 60 mg b.i.d.: p=0.02; combined regimens: p=0.01). Cardiovascular changes reflecting increased sympathetic tone were observed with both duloxetine and desipramine, and both treatments significantly decreased whole body NE turnover (p<0.01). Duloxetine and desipramine were associated with similar mean increases in fractional extraneuronal NE concentration, although these changes did not reach statistical significance. TYR PD30 increased significantly with desipramine dosing (p<0.01). In conclusion, whole-blood measurements confirm that duloxetine inhibits platelet 5-HT uptake in vivo. Urinary and cardiovascular measurements suggest that duloxetine has an effect on NE synthesis and turnover, indicative of NE reuptake inhibition. The lack of a detectable impact of duloxetine on TYR PD30 suggests that this may not be the most sensitive indirect measure of NE reuptake when assessing dual reuptake inhibitors.

Recognition of childhood depression: Personal reminiscences

Prior to 1970, childhood depression was not considered a valid clinical entity by American psychiatrists. One of the early clues was provided in the 1950s by the author’s observation of depressive symptoms in children and young adolescents with undescended testicles. This finding was extended to children with several chronic diseases, many of whom exhibited depressive symptoms as well. Eventually, depressive symptomatology was found in children without any physical disorders. This was followed by the introduction of a diagnostic instrument, called the Children’s Affective Rating Scale (CARS), later converted into a more formal system called the Child Assessment Schedule (CAS). A provisonary classification of childhood depression was published in 1972. Our examination of children with depressive disorders has revealed several modes of family interaction, of which the most important were: separation from important love objects; depreciation and rejection; and affective disorders in parents. Several children with bipolar disorder stimulated our interest in this disorder and led to a pilot study of children of bipolar, lithium-responding parents. Some of these children with bipolar illness had a clear-cut response to lithium and were strong augmenters of the average evoked potentials (EPs). Next, our group investigated the urinary excretion of norepinephrine and its metabolites in chronically depressed children who differed from a normal control group. The foregoing studies, along with major contributions by other child psychiatrists, eventually led to the acceptance of childhood depression as a clinical entity in US psychiatry. The acceptance of juvenile bipolar disorder had to await further research by a new generation of child and adult psychiatrists.

Atorvastatin causes depressor and sympatho-inhibitory effects with upregulation of nitric oxide synthases in stroke-prone spontaneously hypertensive rats

Recent studies have suggested that statins decrease blood pressure in hypertensive animals and upregulate endothelial nitric oxide synthase (eNOS) expression. However, the effects of statins on the expression of nitric oxide synthase (NOS) in the brain and the sympathetic nervous system remain to be elucidated. The aim of this study was thus to examine the effects of atorvastatin on blood pressure, sympathetic nerve activity, and the expression of NOS in stroke-prone spontaneously hypertensive rats (SHRSP) as well as in Wistar-Kyoto (WKY) rats. The animals received atorvastatin (50 mg/kg per day) for 30 days. Systolic blood pressure and heart rate were evaluated using the tail-cuff method. Urinary norepinephrine excretion was measured for 24 h. The expression of eNOS, neuronal NOS (nNOS), and inducible NOS (iNOS) in the brain (cortex, cerebellum, hypothalamus and brainstem), aorta and heart were determined by Western blot analysis. Systolic blood pressure and 24-h urinary norepinephrine excretion were significantly decreased in SHRSP, but not in WKY, after the treatment with atorvastatin. The eNOS and iNOS expression in the brain and aorta was significantly increased in atorvastatin-treated SHRSP and WKY. However, the nNOS expression in the brain was not altered in the atorvastatin-treated group. These results suggest that atorvastatin decreases blood pressure, at least in part via the reduction of sympathetic nervous system activity in SHRSP. They also suggest that this sympatho-inhibitory effect may be mediated by an increase in NO production, with the upregulation of eNOS expression in the brain.

Changes in catecholamine metabolism by ascorbic acid deficiency in spontaneously hypertensive rats unable to synthesize ascorbic acid

We have previously reported the establishment of a novel rat strain, SHR-od, with both spontaneous hypertension and a defect of ascorbic acid biosynthesis. Blood pressure in mature SHR-od fed an ascorbic acid-supplemented diet is over 190–200 mmHg, while it decreased to around 120 mmHg at 4–5 weeks after the cessation of ascorbic acid supplementation. With regard to possible mechanisms of blood pressure lowering, we focused on catecholamine synthesis in adrenal glands, since catecholamine is a major factor for blood pressure regulation and ascorbic acid is a co-factor of dopamine β-hydroxylase (DBH) in catecholamine biosynthesis. Male SHR-od (25-week-old) and normotensive ODS rats with a defect in ascorbic acid biosynthesis (25-week-old) were fed a Funabashi-SP diet with or without ascorbic acid (300 mg/kg diet) for 28 days or 35 days. In SHR-od, systolic blood pressure (191 ± 6 mmHg) began to decrease from day 21 in the ascorbic acid-deficient group, whereas no significant difference was found in ODS rats. In spite of significant lowering of blood pressure, no significant differences were found in catecholamine levels in serum, adrenal glands and brain on day 28. On day 35, however, urinary excretion of norepinephrine and epinephrine in the ascorbic acid-deficient SHR-od were higher at 490% ( P < 0.05) and 460% ( P < 0.05) of the respective control. Serum catecholamine concentrations and the adrenal catecholamine content tended to be higher in the ascorbic acid-deficient SHR-od than the control of SHR-od and reached to similar level in ODS rats. The administration of ascorbic acid (intraperitoneal injection, 60 mg ascorbic acid/kg body weight, once a day) to the ascorbic acid-deficient SHR-od restored blood pressure to the range 180–190 mmHg within two days. These findings indicate that ascorbic acid deficiency affects catecholamine metabolism in the adrenal glands of SHR-od in response to blood pressure lowering, suggesting catecholamines are not involved in the mechanism for the remarkable reduction in blood pressure in response to ascorbic acid deficiency.

Symposium

Symposium

Effect of losartan on nocturnal blood pressure in patients with stroke: comparison with angiotensin converting enzyme inhibitor

Background Treatment of nocturnal hypertension has been reported to be beneficial for primary and secondary prevention of stroke. We compared the effects of angiotensin II antagonist (losartan) and angiotensin converting enzyme inhibitor (quinapril) on nocturnal blood pressure (BP) and sympathetic nervous activity in patients with hypertension and stroke. Methods According to a prospective, randomized, cross-over design, 30 hypertensive patients with a previous history of stroke (25 hemorrhage, 5 infarction) were assigned randomly to receive losartan (50 mg) or quinapril (10 mg) once daily for 4 weeks. The patients were switched to the alternative regimen for an additional 4-week period. In the last week of each treatment, 24-h ambulatory BP monitoring was performed every 30 min, and 24-h urine was collected for the measurement of catecholamine. Results Neither systolic nor diastolic BP during daytime differed between losartan and quinapril treatments, but those during nighttime were lower with losartan treatment than with quinapril treatment. The nocturnal decreases in systolic and diastolic BP were both greater with losartan treatment than with quinapril treatment (systolic BP: 6.1% ± 5.9% v 2.5% ± 6.9%, diastolic BP: 6.4% ± 6.5% v 3.3% ± 7.8%, both P < .05). The nocturnal decrease in urinary norepinephrine excretion was greater with losartan treatment than with quinapril treatment (52.8% ± 9.7% v 42.8% ± 17.2%, P < .05). Conclusions Losartan enhances the nocturnal decrease in ambulatory BP compared with that of quinapril in patients with a previous history of stroke presumably by way of the suppression of nocturnal sympathetic nervous activity.

Relationships between left ventricular mass and the renin-angiotensin system, catecholamines, insulin and leptin.

Several neurohormonal systems have been suggested to stimulate myocardial cell growth, and thus take part in the development of left ventricular (LV) hypertrophy. We studied associations between LV mass and markers of the renin-angiotensin-aldosterone system (RAAS), the sympathetic nervous system, glucose homeostasis and leptin. A total of 115 hypertensive patients with LV hypertrophy and two age- and gender-matched control groups consisting of 38 hypertensive patients without LV hypertrophy and 38 normotensive subjects were included. We examined determinants of the RAAS, plasma levels and 24-h urinary excretions of noradrenaline and adrenaline, plasma proinsulin, insulin, glucose, leptin and LV mass by echocardiography. Plasma renin activity (PRA) and serum aldosterone were higher (both P < 0.001) in the LV hypertrophy group than in patients without LV hypertrophy and normotensive subjects (1.0 +/- 0.8, 0.2 +/- 0.2 and 0.2 +/- 0.2 ng mL(-1) h(-1), and 327 +/- 126, 269 +/- 146 and 221 +/- 80 pmol L(-1), respectively). PRA and aldosterone both related (P < 0.001) to LV mass index (r = 0.44 and 0.27, respectively). Catecholamine levels and excretions were similar in all three groups and did not relate to LV mass index. Proinsulin, insulin and leptin levels were all elevated in the hypertensive patients (P < 0.01), but proinsulin, insulin, insulin sensitivity (by the homeostasis model assessment) and leptin did not relate to LV geometry, when indexed for body size. Plasma renin activity and serum aldosterone levels are elevated in hypertensive LV hypertrophy and relate to LV mass index. In addition to blood pressure, activation of the RAAS may be an important nonhaemodynamic mechanism in the control of LV hypertrophy.

Effects of pressure on the skin exerted by clothing on responses of urinary catecholamines and cortisol, heart rate and nocturnal urinary melatonin in humans.

The study investigated how the pressure exerted on the skin by clothing worn while working in the daytime affected the urinary excretion of adrenaline, noradrenaline and cortisol, heart rate, and also melatonin secretion at night. Nine young women (experiment I) and seven young women (experiment II) participated. Participants wore either a 100% cotton jacket (tight clothes, TC) or a 100% cotton T-shirt (loose clothes, LC). Loose-fitting, 100% cotton tank tops and panties were worn as underwear in both the TC and the LC groups. The main results can be summarized as follows: (1) urinary excretion of adrenaline, noradrenaline and cortisol was facilitated, and the amounts of urinary excretion were significantly higher when TC were worn. Heart rate was significantly higher in the TC group; (2) nocturnal urinary melatonin excretion was significantly greater in the TC group. These results are discussed in terms of an enhancement of diurnal sympathetic nervous system activity caused by pressure on the skin produced by tight clothing.

Decreased skeletal muscle insulin receptors in high-fat diet-related hypertensive rats

We investigated the number of insulin receptors in skeletal muscle in long-term high fat-fed hypertensive rats. Male Sprague-Dawley rats were fed a high-fat (FAT) diet or a high-carbohydrate (CHO) diet. After 16 wk of feeding, the total weight of the adipose tissue deposits was significantly higher in the FAT diet treated group than in the CHO diet treated group. Plasma insulin and glucose levels, blood pressure (BP) and urinary excretion of norepinephrine and epinephrine were significantly higher in the FAT diet treated group. The numbers of insulin receptor in soleus and gastrocnemius muscles were significantly fewer in the FAT diet treated group. These results suggest that the decrease in the number of skeletal muscle insulin receptors may be associated with severe insulin resistance and FAT diet-related BP elevation.

Caffeine Affects Cardiovascular and Neuroendocrine Activation at Work and Home

Objective This study investigated the effects of moderate doses of caffeine on ambulatory blood pressure and heart rate, urinary excretion of epinephrine, norepinephrine, and cortisol, and subjective measures of stress during normal activities at work and at home in the evening. Methods Healthy, nonsmoking, habitual coffee drinkers (N = 47) participated in 3 days of ambulatory study. After a day of ad lib caffeine consumption, caffeine (500 mg) and placebo were administered double-blind in counter-balanced order on separate workdays. Ambulatory blood pressure and heart rate were monitored from the start of the workday until bedtime. Urinary excretion of catecholamines and cortisol was assessed during the workday and evening. Results Caffeine administration significantly raised average ambulatory blood pressure during the workday and evening by 4/3 mm Hg and reduced average heart rate by 2 bpm. Caffeine also increased by 32% the levels of free epinephrine excreted during the workday and the evening. In addition, caffeine amplified the increases in blood pressure and heart rate associated with higher levels of self-reported stress during the activities of the day. Effects were undiminished through the evening until bedtime. Conclusions Caffeine has significant hemodynamic and humoral effects in habitual coffee drinkers that persist for many hours during the activities of everyday life. Furthermore, caffeine may exaggerate sympathetic adrenal-medullary responses to the stressful events of normal daily life. Repeated daily blood pressure elevations and increases in stress reactivity caused by caffeine consumption could contribute to an increased risk of coronary heart disease in the adult population.

Neuropeptide Y.

Neuropeptide Y.

Excess norepinephrine impairs both endothelium-dependent and -independent vasodilation in patients with pheochromocytoma.

There is little information concerning the interaction of nitric oxide and norepinephrine (NE) on endothelial function in humans. The purpose of this study was to determine whether endothelial function is impaired by NE secreted from patients with pheochromocytoma (pheo) and whether surgical resection of the tumor improves endothelial function in these patients. We evaluated the forearm blood flow (FBF) response to acetylcholine (ACh), an endothelium-dependent vasodilator, and isosorbide dinitrate (ISDN), an endothelium-independent vasodilator, before and after adrenalectomy in 8 pheo patients, 20 normotensive subjects, and 20 patients with essential hypertension. FBF was measured using a mercury-filled silastic strain-gauge plethysmograph. The FBF response to ACh was the greatest in normotensive subjects and the least in pheo patients. The FBF response to ISDN was significantly less in pheo patients than in the other 2 groups, which had similar responses to ISDN. Adrenalectomy significantly decreased plasma and urinary NE, systolic and diastolic blood pressures, heart rate, and forearm vascular resistance. After adrenalectomy, FBF responses to both ACh and ISDN were enhanced in all pheo patients. The ratio of maximal ACh-stimulated FBF to maximal ISDN-stimulated FBF was significantly higher after adrenalectomy than before adrenalectomy (2.1 +/- 0.4 versus 1.1 +/- 0.1; P<0.05). The increase in maximal FBF response to ACh correlated significantly with the decrease in urinary excretion of NE (r=-0.62, P<0.01). These findings suggest that excess NE from pheo may predominantly impair endothelium-dependent vasodilation in humans.

Cardiovascular Effects of Overexpression of Endothelial Nitric Oxide Synthase in the Rostral Ventrolateral Medulla in Stroke-Prone Spontaneously Hypertensive Rats

We have previously demonstrated that the overexpression of endothelial NO synthase (eNOS) in the rostral ventrolateral medulla (RVLM) decreases blood pressure, heart rate, and sympathetic nerve activity via an increase in gamma-amino butyric acid release in normotensive Wistar-Kyoto rats (WKY). Stroke-prone spontaneously hypertensive rats (SHRSP) appear to have reductions of NO production and GABA release in the RVLM. The aim of this study was to determine whether the effects of the increase in NO production in the RVLM in SHRSP are different from those in WKY. We transfected adenovirus vectors encoding either eNOS (AdeNOS) or beta-galactosidase (Adbetagal) into the RVLM of both strains. In the AdeNOS-treated group, mean arterial blood pressure and heart rate in the conscious state were significantly decreased at day 7 after the gene transfer in both strains. The decreases in mean arterial blood pressure and heart rate were significantly greater in SHRSP than in WKY. Urinary norepinephrine excretion was also decreased to a greater degree in SHRSP than in WKY after the gene transfer. The pressor response evoked by bicuculline into the RVLM of WKY was greater than that of SHRSP in the nontransfected group. However, in the AdeNOS-treated group, the pressor response did not differ between SHRSP and WKY after the gene transfer. These results indicate that the increase in NO production evoked by the overexpression of eNOS in the RVLM causes greater depressor and sympathoinhibitory responses in SHRSP than in WKY by improving an inhibitory action of GABA on the RVLM neurons.