Sympatho-adrenomedullary Activity Research Articles

Delovanje svakodnevnog intenzivnog vežbanja na asimetriju simpato-adrenomedularne aktivnosti

Delovanje svakodnevnog intenzivnog vežbanja na asimetriju simpato-adrenomedularne aktivnosti

Elevated biomarkers of sympatho-adrenomedullary activity linked to e-waste air pollutant exposure in preschool children

Air pollution is a risk factor for cardiovascular disease (CVD), and cardiovascular regulatory changes in childhood contribute to the development and progression of cardiovascular events at older ages. The aim of the study was to investigate the effect of air pollutant exposure on the child sympatho-adrenomedullary (SAM) system, which plays a vital role in regulating and controlling the cardiovascular system. Two plasma biomarkers (plasma epinephrine and norepinephrine) of SAM activity and heart rate were measured in preschool children (n = 228) living in Guiyu, and native (n = 104) and non-native children (n = 91) living in a reference area (Haojiang) for >1 year. Air pollution data, over the 4-months before the health examination, was also collected. Environmental PM2.5, PM10, SO2, NO2 and CO, plasma norepinephrine and heart rate of the e-waste recycling area were significantly higher than for the non-e-waste recycling area. However, there was no difference in plasma norepinephrine and heart rate between native children living in the non-e-waste recycling area and non-native children living in the non-e-waste recycling area. PM2.5, PM10, SO2 and NO2 data, over the 30-day and the 4-month average of pollution before the health examination, showed a positive association with plasma norepinephrine level. PM2.5, PM10, SO2, NO2 and CO concentrations, over the 24 h of the day of the health examination, the 3 previous 24-hour periods before the health examination, and the 24 h after the health examination, were related to increase in heart rate. At the same time, plasma norepinephrine and heart rate on children in the high air pollution level group (≤50-m radius of family-run workshops) were higher than those in the low air pollution level group. Our results suggest that air pollution exposure in e-waste recycling areas could result in an increase in heart rate and plasma norepinephrine, implying e-waste air pollutant exposure impairs the SAM system in children.

17β‐Estradiol inhibits isoproterenol activated lipolysis in murine adipocytes

Stress stimulates sympatho‐adrenomedullary activity and lipolysis in adipocytes. Increase in plasma free fatty acids has been demonstrated to be a major link between obesity and insulin resistance. However, there are many reports describing the anti‐obesity effect of estrogen. This study investigated the effect of estrogen on isoproterenol (ISO) activated lipolysis in murine adipocytes. ISO (5 μM) and 17β‐Estradiol (E2) was added to mature 3T3‐L1 adipocytes in 6 well plates. After 2 hr incubation at 37 °C in 5% CO2/95% air, the glycerol concentration in DMEM medium was measured. Effects of β2‐adrenoceptor inhibitor (yohimbine, 50 μM), phosphodiesterase inhibitor (cilostamide, 2 μM) and estrogen receptor blocker (tamoxifen, 10 μM) on the inhibitory effect of lipolysis of E2 were also tested. Further, effect of E2 on cAMP production and hormone sensitive lipase (HSL) activity in 3T3‐L1 adipocytes were investigated. E2 (5–50 μM) inhibited ISO activated lipolysis in 3T3‐L1 adipocytes dose‐dependently. Yohimbine, cilostamide and tamoxifen did not abolish the inhibitory effect of E2 on ISO activated lipolysis. E2 inhibited HSL activity, whereas E2 did not reverse the increased cAMP level induced by ISO stimulation. These results suggest that E2 exerts its inhibitory effect of ISO activated lipolysis by inhibition somewhere down‐stream of cAMP production but up‐stream of the HSL signaling pathway.

Excretion of catecholamines in rats, mice and chicken

Stress assessment favours methods, which do not interfere with an animal’s endocrine status. To develop such non-invasive methods, detailed knowledge about the excretion of hormone metabolites in the faeces and urine is necessary. Our study was therefore designed to generate basic information about catecholamine excretion in rats, mice and chickens. After administration of 3H-epinephrine or 3H-norepinephrine to male and female rats, mice and chickens, all voided excreta were collected for 4 weeks, 3 weeks or for 10 days, respectively. Peak concentrations of radioactivity appeared in one of the first urinary samples of mice and rats and in the first droppings in chickens 0.2–7.2 h after injection. In rats, between 77.3 and 95.6% of the recovered catecholamine metabolites were found in the urine, while in mice, a mean of 76.3% were excreted in the urine. Peak concentrations in the faeces were found 7.4 h post injection in mice, and after about 16.4 h in rats (means). Our study provides valuable data about the route and the profile of catecholamine excretion in three frequently used species of laboratory animals. This represents the first step in the development of a reliable, non-invasive quantification of epinephrine and norepinephrine to monitor sympatho-adrenomedullary activity, although promising results for the development of a non-invasive method were found only for the chicken.

Molecular aspects of adrenal regulation for circadian glucocorticoid synthesis by chronic voluntary exercise

Chronic voluntary running of mice is known to increase the circadian peak of plasma corticosterone without change in the level of adrenocorticotropic hormone (ACTH). In order to investigate how chronic exercise modulates the circadian HPA axis, we used two weeks of voluntary wheel running of mice and confirmed the significant increase of the circadian peak of plasma corticosterone without alteration in ACTH level. To elucidate the mechanisms of exercise modulation on corticosterone synthesis, we first examined the levels of transcripts involved in corticosterone synthesis of the adrenal gland. Among them, only steroidogenic acute regulatory protein (StAR), the rate-limiting factor that transfers substrate cholesterol into inner mitochondrial membrane, showed significantly higher expression in the exercise group. Since the splanchnic nerve input to the adrenal gland has been reported as a factor involved in the direct modulation of corticosterone synthesis, we next examined the expression levels of enzymes for the catecholamine synthesis as indices of sympatho-adrenomedullary activity. We found that the only rate-limiting enzyme, tyrosine hydroxylase (TH), was significantly higher in the adrenals of exercise group. In addition to the increment of StAR and TH mRNA in response to the chronic exercise, surprisingly, we found only these factors showed the circadian variation in its expression levels that was correlated to the circadian rhythm of corticosterone. Chronic exercise seems to alter the circadian corticosterone synthesis, at least partially via altering the levels of circadian-regulated transcripts, StAR and TH of the adrenal gland.

Endocrine and Immunologic Parameters Indicative of 6-Month Prognosis After the Onset of Low Back Pain or Neck/Shoulder Pain

Prospective study. To evaluate the prognosis of spine disease by investigating biologic parameters reflecting different physiologic or psychophysiological systems in men and women with acute onset of low back or neck/shoulder complaints. Psychosocial factors may be of importance to the etiology and prognosis of musculoskeletal disorders. The possible mechanisms, however, remain unclear. Stress-induced long-lasting energy mobilization resulting in inhibited anabolism has been discussed. Using a theoretical framework within stress physiology, such psychophysiological processes were recorded by measures of substances representing the anabolic, catabolic, immunologic, and opioid systems. The study comprised 67 working men and women 21 to 59 years of age seeking care by any caregiver for acute low back and/or neck/shoulder pain. Blood samples were taken and analyzed for 3 methyl 5hydroxy phenylethylene glycol (MHPG, reflecting sympathoadrenomedullary activity), DHEA-s (anabolism), immunoglobulin E, interleukin 6 (immune activity), and beta-endorphin (pain regulation). The participants were followed up for 6 months after the blood samples had been drawn. In women, low MHPG, low DHEA-s, and low beta-endorphin predicted persistent disability due to low back complaints. Few significant findings were made for self-reported pain, for neck/shoulder complaints, and for men. Disturbances of the regulation of certain biologic parameters might be indicators of a prolonged course of low back disease in women. Prospective studies are necessary to enable causal conclusions.

Plasma catecholamine and cardiovascular responses to physostigmine in Alzheimer's disease and aging.

Stimulation of brain cholinergic systems increases activity of both the sympathoneural (SN) and sympathoadrenomedullary (SAM) components of the peripheral sympathetic nervous system. Because presynaptic cholinergic neuron numbers are substantially reduced in Alzheimer's disease (AD), we predicted decreased responsiveness in AD of plasma norepinephrine (NE), an estimate of SN activity, and of epinephrine (EPI), an estimate of SAM activity, to central cholinergic stimulation by the cholinesterase inhibitor physostigmine (0.0125 mg/kg i.v.). Because previous studies have demonstrated that normal human aging increases SN activity but not SAM activity, we specifically hypothesized: (1) a smaller NE response to physostigmine in subjects with mild to moderate AD (n=11; age 72+/-2 yrs; mini-mental state exam [MMSE] scores of 19+/-2) than in healthy older subjects (n=20; age 71+/-1 yrs); and (2) a smaller EPI response in AD subjects than in either healthy older or healthy young subjects (n=9; age 27+/-2 yrs). Unexpectedly, the plasma NE increase following physostigmine only achieved significance in AD subjects and plasma EPI responses were greater in both AD and older subjects than in young subjects. Blood pressure responses to physostigmine were consistent with the catecholamine responses. These data suggest that the presence of mild to moderate AD increases the SN response to cholinergic stimulation and that both AD and normal aging increase the SAM response to cholinergic stimulation. As a result, plasma catecholamine responses to physostigmine do not appear to be useful peripheral neuroendocrine estimates of the severity of brain cholinergic deficits in mild to moderate AD.

Twenty-four-hour rhythms of plasma catecholamines and their relation to cardiovascular parameters in healthy young men.

Diurnal and ultradian rhythms of plasma norepinephrine and epinephrine and their role in the regulation of cardiovascular parameters were investigated over 24 h of recumbency in a group of five men. Catecholamines were measured at 10 min intervals, and blood pressure and heart rate were recorded continuously. Norepinephrine and epinephrine rapidly fluctuated in each subject, with no obvious diurnal rhythm. Spectral analysis suggested two ultradian rhythms with periods of around 12 h and 50-100 min for both catecholamines. The pulse detection programs PULSAR and CLUSTER revealed 20-30 pulses/24 h for norepinephrine and epinephrine, with a significant correlation between the two rhythms (r = 0.63-0.80, P < 0.001). Neither the frequency nor the amplitude of these rapid fluctuations differed between day and night. Arousal in the morning caused a small increase in plasma catecholamines and getting out of bed a large increase. Thus changes in posture and activity are the main influences on the diurnal variations of plasma catecholamines reported previously, while the ultradian rhythms of sympathoadrenomedullary activity appear to be of intrinsic origin. Blood pressure and heart rate exhibited a diurnal rhythm with a nightly decrease. Arousal and rising from bed increased blood pressure and heart rate significantly. Although the amplitude of the rapid fluctuations of plasma catecholamines at times exceeded those caused by postural changes in the morning, when both plasma norepinephrine and epinephrine levels correlated highly with all cardiovascular parameters, correlations were not significant during recumbency. Thus the intrinsic ultradian fluctuations of plasma catecholamines appear not to be involved in the control of cardiovascular parameters during recumbency, and the increase in blood pressure and heart rate in the morning appears to be controlled by direct sympathetic neural input to the heart and vasculature in response to changes in activity and posture rather than by an endogenous surge of plasma catecholamines.

Adrenergic and cholinergic modulation of insulin secretion in non-lactating cows exposed to heat

The inhibition of insulin secretion in sheep exposed to cold has been reported to be mediated through adrenergic α receptors stimulated by sympathoadrenomedullary activity (Sasaki and Takahashi, 1980). Insulin secretion in Holstein non-lactating cows in response to various secretogogues was also suppressed during heat exposure (Itoh et al., unpublished data), however it is not obvious whether these responses were related to neural controls or not. However acetylcholine (parasympathetic nervous system neurotransmitter) has been shown to promote the release of glucagon and insulin (Jones et al., 1991). Therefore, the objective of this study was to examine the participation of adrenergic and cholinergic neural control on insulin secretion in thermoneutral and hot environments in non-lactating cows by administering, adrenergic and cholinergic blockers with an intravenous injection of glucose.

P.5.009 - Sympatho-adrenomedullary activity during mental stress and orthostatic challenge: Effects of alprozolam and lorazepam

P.5.009 - Sympatho-adrenomedullary activity during mental stress and orthostatic challenge: Effects of alprozolam and lorazepam

Chronic alpha-1-adrenergic blockade increases sympathoneural but not adrenomedullary activity in patients with essential hypertension

Doxazosin, a selective alpha1-adrenoceptor antagonist, lowers blood pressure by reducing peripheral vascular resistance without causing reflex tachycardia. To discover whether antihypertensive treatment with an alpha1-adrenoceptor blocker is accompanied by an increase in sympathoadrenomedullary activity, we studied plasma catecholamine kinetics before and during treatment with doxazosin. Eleven patients with essential hypertension were studied before and after 3 months' treatment with doxazosin (4-8 mg a day). 3H-noradrenaline and 3H-adrenaline were infused simultaneously and blood samples were collected to calculate plasma catecholamine kinetics before and during sympatho-adrenomedullary stimulation (lower-body negative pressure). Doxazosin decreased systolic and diastolic blood pressure and forearm vascular resistance, whereas the heart rate did not change significantly. During doxazosin, baseline arterial plasma noradrenaline increased from 0.97 +/- 0.07 to 1.21 +/- 0.07 nmol/l, and this appeared to be due to an increase in total body noradrenaline spillover from 1.54 +/- 0.15 to 1.84 +/- 0.16 nmol/min; noradrenaline clearance did not change significantly. Forearm noradrenaline spillover also increased, from 0.89 +/- 0.18 to 1.48 +/- 0.23 pmol/100 ml per min. In contrast, arterial plasma adrenaline, total body adrenaline spillover and adrenaline clearance were not significantly affected by doxazosin treatment. The response of plasma noradrenaline and total body and forearm spillover of noradrenaline to lower-body negative pressure (-40 mmHg) was significantly increased during doxazosin administration, whereas the response of the adrenaline kinetic parameters were not altered. The blood pressure reduction induced by a chronic administration of the alpha1-adrenoceptor blocker doxazosin elicits a baroreceptor-mediated reflexive increase in sympathoneural but not in adrenomedullary activity. The latter finding might partly explain why the heart rate is not increased during chronic treatment with this alpha1-adrenoceptor blocking drug.

Free plasma catecholamine levels in healthy subjects: a basal and dynamic study. The influence of age.

We studied the levels of free plasma noradrenaline (norepinephrine, NE), adrenaline (epinephrine, E), and dopamine (DA) in 143 normal subjects, either basally or, in a part of them, in response to four tests stimulating the sympathoadrenomedullary activity: the tilt-table test (TTT), the cold-pressor test (CPT), the mental-arithmetic test (MAT), and the insulin tolerance test (ITT). In both cases we evaluated the influence of age, which is considered the main physiological variable affecting the peripheral sympathetic activity. A normal distribution of values was observed, in the basal study, only for NE, while E and particularly, DA levels were distributed in an non-homogeneous fashion; a direct correlation was observed between age of subjects and NE levels, while neither E, nor DA levels showed any correlation with the aging process; sex did not influence any of the catecholamines. In the dynamic study, CPT, ITT and, above all, TTT elicited a significant rise in NE levels, while the E release was greatly stimulated by the insulin-induced hypoglycaemia. Neither NE, nor E levels rose after the MAT stimulation. Also in this case, the elderly showed an increased noradrenergic responsiveness when compared with the young subjects, confirming the existence of an 'up-regulation' of the peripheral sympathetic tone in old people.

Placebo-Controlled Trial of Dexamethasone for Chronic Biliary Pain After Cholecystectomy

Activation of the sympathetic nervous system appears to be relevant in some patients with unexplained pain after cholecystectomy, particularly those who show increases in plasma transaminase activity after challenge with morphine (morphine responders). In this study, the hypothesis that dexamethasone would improve chronic biliary pain, perhaps by suppressing activation of the sympathetic nervous system, was tested in a double-blind, placebo-controlled, cross-over trial in 20 patients, 10 morphine responders and 10 nonresponders. Before treatment with dexamethasone and placebo, urinary excretion of norepinephrine (NE) was significantly higher (p less than 0.05) in morphine responders than in nonresponders. During treatment with dexamethasone, 1 mg each night for 4 weeks, neither morphine responders nor nonresponders showed a significant improvement in pain or nausea or a significant reduction in sympathoadrenomedullary activity as assessed by urinary excretion of catecholamines. At the dose administered, dexamethasone was unhelpful for chronic pain after cholecystectomy and did not result in suppression of the sympathetic nervous system as assessed by urinary excretion of NE.

Increased sympathoadrenomedullary activity and left ventricular hypertrophy in young patients with borderline hypertension

Echocardiographic dimensions and endocrinological examination were performed in 71 young patients with borderline hypertension (BHT) and 31 age-matched normotensive subjects (NT). Patients with BHT had significantly higher relative wall thickness (RWT) and left ventricular mass index than NT, although all BHT patients showed no asymmetric increase in the ratio of septal to posterior wall thickness. Moreover, these BHT patients demonstrated an increased cardiac output and an augmented mean circumferential fiber shortening rate (mean Vcf), suggesting left ventricular hyperfunction. Overall, there was a positive correlation between RWT and mean Vcf in BHT patients (r = 0.700, P less than 0.001), although there was no significant relationship between RWT and blood pressure. Furthermore, these BHT patients had higher plasma epinephrine (PE) and plasma renin activity compared to NT, suggesting the increased sympathoadrenomedullary activity in BHT. These BHT patients were divided into two groups with regards to PE levels; namely a high PE group (PE greater than or equal to 46 pg/ml) and a normal PE group (PE less than 46 pg/ml). The high PE group had a significantly higher mean Vcf and RWT than the normal PE group. These findings suggest that in young BHT patients left ventricular hypertrophy could be related to abnormalities of the sympathoadrenomedullary systems.

Venous versus arterial forearm catecholamines as an index of overall sympatho-adrenomedullary activity.

The metabolism of norepinephrine (NE) and epinephrine (EPI) in peripheral tissues limits the use of venous plasma levels of these parameters as an index of overall sympathetic or adrenomedullary activity. Therefore venous (deep antecubital vein) and arterial (brachial artery) concentrations of NE and EPI were compared in 16 hypertensive subjects. NE and EPI were determined after 30 min supine rest, and immediately before and after isometric exercise, cold provocation, head-up tilting (OST) and Stroop's colour word test (CWT). At rest venous NE exceeds arterial NE. Assuming similar fractional extractions (FE) of NE and EPI, 46 +/- 14% (mean +/- SD) of venous NE appeared to be produced locally. Despite this considerable local production venous and arterial levels of NE were closely correlated (r = 0.92). At rest venous EPI was 42 +/- 13% lower than arterial EPI, but since the interindividual variation of the FE of EPI was relatively small and independent of arterial levels, venous and arterial levels were also closely correlated (r = 0.82). All four tests caused an increase in arterial and venous NE, whereas EPI did not change. Responses of arterial and venous NE were only correlated after OST and CWT. It is concluded that at rest, but not invariably so during different forms of sympatho-adrenal activation, arterial plasma concentrations of NE and EPI can be substituted for by their respective venous equivalents.

Pharmacologic and tracer methods to study sympathetic function in primary hypertension.

Systemically infused tritiated norepinephrine (NE) was used to estimate total body NE spillover into arterial blood during mental challenge (playing a video game) in 18 young (mean age 35 years old) patients with essential hypertension and 20 normotensives of similar age. Arterial NE, epinephrine (E), and total body NE spillover at baseline did not differ between the groups. During the game, total body NE spillover increased significantly in both groups, with the increments related directly to the pressor responses. Mean increments in total body NE spillover, arterial E, and mean arterial pressure were larger in the hypertensives (204 vs 91 ng/min, 33 vs 9 pg/ml, and 16 vs 12 mm Hg). The hypertensives increased total peripheral resistance during the game, whereas the normotensive group did not. Intravenous administration of yohimbine was used to increase NE spillover. Pressor responses to yohimbine were related to responses of arterial NE. The hypertensive group had a larger mean increment in blood pressure and arterial NE than did the normotensive group during yohimbine, due to excessive responses in a subgroup of about 1/3 of the patients. Patients with essential hypertension can have excessive sympathoadrenomedullary responsiveness related to excessive pressor responses, even when sympathoadrenomedullary activity at rest is normal.

Evidence for increased sympatho-adrenomedullary activity in young subjects with borderline hypertension.

Three different studies were performed to estimate the sympatho-adrenomedullary activity in young subjects with borderline hypertension (BHT, n = 40), compared with age-matched normotensive subjects (NT, n = 24). In the first study, 23 BHT and 9 NT were subjected to isometric stress by maintaining handgrip at the 30% level of maximal voluntary contraction for 3 min. The response of plasma total catecholamines at the second and third min during the isometric exercise were greater in BHT than in NT (98.9 +/- 24.3 vs. 18.0 +/- 30.7 and 93.0 +/- 12.6 vs. 47.1 +/- 15.4 pg/ml, respectively, p less than 0.05). In the second study, the effects of intravenous glucagon injection (1 USP unit) were studied in 12 BHT and 9 NT. The increments of plasma epinephrine (E) at 2 and 3 min after injection were significantly greater in BHT than those in NT: 44.1 +/- 12.3 vs. 5.1 +/- 4.4 pg/ml, and 68.9 +/- 13.2 vs 32.1 +/- 8.9 pg/ml, respectively, p less than 0.05. In the last study, the pressor effects of intravenous norepinephrine (NE) infusion (100 and 200 ng/kg/min for 15 min) were examined in 17 BHT and 15 NT under three different sodium balances: regular customary diet, treatment with diuretics and high-sodium diet. Treatment with diuretics decreased and high-sodium diet increased the pressor response to NE in both groups, but there were no significant differences in NE reactivity between 2 groups throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Sympathoadrenomedullary hyper-responsiveness to yohimbine in juvenile spontaneously hypertensive rats

We examined responses of arterial plasma levels of the sympathetic neurotransmitter, norepinephrine (NE), of the adrenomedullary hormone, epinephrine (E), and of the intraneuronal NE metabolite, dihydroxyphenylglycol (DHPG), after intravenous administration of the alpha-2 adrenoceptor antagonist, yohimbine, in conscious, freely-moving juvenile (4-week old) o mature (12-week old) rats with spontaneous hypertension (SHRs) and their normotensive Wistar-Kyoto (WKY) controls. Mature SHRs and WKY rats had similar levels of plasma catechols at rest, whereas juvenile SHRs had significantly higher levels of NE (400 +/− 109 (SD) vs 233 +/− 62 pg/ml), E (371 +/− 168 vs 148 +/− 67 pg/ml), and DHPG (800 +/− 147 vs 589 +/− 54 pg/ml). After yohimbine, average responses of NE in the juvenile SHRs were more than 5 times, of E more than 7 times, and of DHPG more than 11 times those of the juvenile WKY rats. The responses of plasma catechols to yohimbine were not excessive in mature 12-week old SHRs. The results demonstrate increased sympathoadrenomedullary activity at rest and markedly enhanced sympathoadrenomedullary responsiveness to yohimbine in juvenile but not mature SHRs and are consistent with the hypothesis that early in the development of hypertension in this laboratory animal model there is an abnormal dependence on central neural alpha-2 adrenoceptors as part of an incompletely successful compensatory mechanism for limiting sympathetic outflow.

Increased sympatho-adrenomedullary activity in young patients with borderline hypertension: hyperresponses to isometric stress and glucagon injection

The purpose of this study was to estimate the sympatho-adrenomedullary activity in young patients with borderline hypertension (BHT, n=23), compared with age-matched normotensive subjects (NT, n=9), so that two studies were performed as follows: they were subjected to isometric stress, by maintaining handgrip at the 30% level of maximal voluntary contraction for three minutes. With the exercise blood pressure and pulse rate increased to the same degree in BHT as in NT. In contrast, the response of plasma total catecholamine (plasma epinephrine plus norepinephrine) at the end of this isometric exercise was greater in BHT than in NT (93.0 +/- 12.6 in BHT vs. 47.1 +/- 15.4pg/ml in NT). Moreover, the effects of intravenous glucagon injection (1 USP unit) were studied in twelve subjects of BHT (n = 12) and all of NT (n = 9). The injection of glucagon induced a transient increase in pulse rate, but there was no significant difference in the elevation of pulse rate with glucagon between BHT and NT. Plasma epinephrine also increased temporarily, and returned to the baseline within ten minutes after injection. The increments of plasma epinephrine at two and three minutes after injection were significantly greater in BHT than those in NT: 44.1 +/- 12.3 vs. 5.1 +/- 4.4pg/ml, and 68.9 +/- 13.2 vs. 32.1 +/- 8.9 pg/ml, respectively. Thus, patients with borderline hypertension had the augmented response of plasma catecholamine to both isometric exercise and glucagon stimulation. Evidence presented suggests that the responses of sympathetic nervous system and adrenal medulla to stress are increased in young patients with borderline hypertension. Moreover, the augmented response of sympatho-adrenomedullary system to stress may be involved in the development of essential hypertension.

Effect of decreased dopamine synthesis on the development of hypertension induced by salt loading in spontaneously hypertensive rats.

To clarify role of dopamine in the development of hypertension, the effect of a dopamine synthesis inhibitor on blood pressure and urinary output of catecholamines was investigated in spontaneously hypertensive rats (SHR) fed with high sodium diet. Rats were orally given carbidopa, an inhibitor of peripheral DOPA decarboxylase, or the vehicle for 4 weeks. Carbidopa administration accelerated significantly the development of hypertension as compared to the control SHRs with the vehicle. Carbidopa administration resulted in a significant decrease of urinary excreted sodium, urinary dopamine and renal content of dopamine. Conversely, carbidopa administration resulted in a significant increase of urinary excreted norepinephrine, urinary epinephrine and renal content of norepinephrine as compared with control SHRs. These results suggest that decreased dopamine synthesis in kidneys and probably other peripheral tissue accelerates the development of hypertension, mediated by a decrease of natriuresis and an enhancement of sympatho-adrenomedullary activity. Dopamine plays an important role in its protective action against the development of hypertension enhanced by salt loading, and decreased dopaminergic mechanisms accelerated hypertension in SHR.