Higher Plasma Norepinephrine Research Articles

Abnormal relationship between sodium intake and sympathetic nervous system activity in salt-sensitive patients with essential hypertension

To examine the mechanisms underlying the sensitivity to sodium intake in a subset of patients with essential hypertension, we studied the effects of different sodium intake (10, 100, 200 mEq/day) on blood pressure, the function of the renin-angiotensin-aldosterone system, and on blood levels of catecholamines in 20 patients with essential hypertension and 10 normal subjects. Mean blood pressure (MBP) was not different in hypertensive and normal subjects during low sodium diet. But, with high sodium intake, MBP increased by at least 10% in 12 patients (salt-sensitive), whereas in the remaining 8 patients (salt-resistant) and in normal subjects, MBP did not change significantly. This phenomenon cannot be attributed to differences in sodium retention because the percent change in body weight ad the urinary sodium excretion in the salt-sensitive patients was not different than it was in salt-resistant patients or in normal subjects. The observed difference in blood pressure response to high sodium intake in salt-sensitive patients is also not dependent on an impaired suppressibility of the renin-angiotensin-aldosterone system because there were no significant differences in the basal levels of PRA and aldosterone between the groups, and because the orthostatic increments in PRA were significantly lower in salt sensitive than they were in the salt-resistant patients and in normal subjects. Plasma norepinephrine (NE) levels were not significantly different between normal subjects or hypertensive patients while on low sodium intake. But during high sodium intake, they decreased significantly (P less than 0.05) in normal subjects (from 22 +/- 3.4 to 12 +/- 2.3 ng/dl) and in salt-resistant patients (from 17 +/- 4.5 to 13 +/- 2.4 ng/dl) but not in salt-sensitive patients (from 20 +/- 1.9 to 22 +/- 3.2 ng/dl). Furthermore, the majority of salt-sensitive patients displayed inappropriately high plasma NE in relation to their urine excretion of sodium during high sodium intake. Finally, the increments in plasma NE after 5 min of standing were significantly greater in salt-sensitive patients than they were in salt-resistant patients and normal subjects during both low or high sodium intake. These data indicate that a subset of patients with essential hypertension may have impaired suppressibility of plasma NE during high sodium intake, which suggests hyperactivity of the sympathetic nervous system in these patients. These aberrations may be responsible for the increase in MBP in the salt-sensitive patients during high sodium intake.

Adrenergic activity in systolic hypertension.

Basal hemodynamics and plasma catecholamines were measured in 10 patients with systolic hypertension, 7 males and 3 females, aged 38-69 years (Group 1), and in 10 patients with systolic and diastolic hypertension, 7 males and 3 females, aged 40-65 years (Group 2); the same measurements were repeated after acute pharmacological alpha and beta-blockade with Labetalol, 100 mg iv, or Propranolol, 10 mg iv, plus Phentolamine, 10 mg iv. In patients of Group 1 plasma noradrenaline was inversely related to systolic arterial pressure and to stroke index and was directly related to heart rate. In patients of Group 2 plasma noradrenaline was directly related to systolic arterial pressure. After acute alpha and beta-blockade the degree of reduction of systolic arterial pressure was directly related to basal plasma noradrenaline in both groups; systolic arterial pressure was reduced to normotensive levels in 5 patients of Group 1 who had high basal plasma noradrenaline values. These results confirm some of our previous findings and suggest that in some patients with systolic hypertension adrenergic activity is increased and may have a significant role in maintaining high blood pressure values.

Relationship between plasma catecholamines and urinary catecholamine excretion rates in normal subjects and certain diseased states.

Relationships between plasma norepinephrine (PNE) or epinephrine (PE) and urinary norepinephrine (UNE) or epinephrine (UE) excretion rates were studied in 37 normal subjects, 39 patients with benign essential hypertension, 23 with unilateral renal hypertension, and 20 with bilateral renal disease (serum creatinine 2.3 +/- 2.6 mg/100 ml). measurements were also performed after 6 weeks of diuretic treatment in 27 normal subjects and all patients with essential hypertension. In the untreated state, PNE and UNE values were generally normal in essential or unilateral renal hypertension; PNE tended to be decreased in diabetics and increased in bilateral renal disease. Diuretic treatment caused a tendency for slightly increased PNE and UNE. UNE correlated significantly with supine PNE or upright PNE or their mean value, and this relationship appeared to be comparable between untreated normal subjects and the various patients groups, except for a tendency for slightly higher PNE at given UNE values in bilateral renal disease. No significant correlations between UE and PE were apparent in the normal subjects or patient groups. These data demonstrate a dissociation of UE from PE levels. In contrast, UNE is an approximative index of PNE, and this relationship appeared to be generally unaltered in essential or unilateral renal hypertension. In patients with bilateral renal disease the slight shift of this relationship indicates that consideration of renal function is necessary for interpretation of NE levels.

Plasma norepinephrine in stroke.

Cardiac arrhythmias, myocardial necrosis and ECG abnormalities in stroke may result from abnormally high levels of sympathetic activity. To examine this possibility, plasma norepinephrine, epinephrine and dopamine were measured in 74 patients with cerebral infarction, 18 with transient ischemic attacks and 33 non-stroke controls. Mean norepinephrine, epinephrine and dopamine values (pg/ml) in cerebral infarction (433.2, 81.6, 75.6 were higher (p less than 0.01) than in controls (281.1, 60.1, 40.5, respectively). Transient ischemic attacks produced values intermediate to these two groups (391.3, 80.9, 54.9). The elevated catecholamine concentrations in cerebral infarction could not be explained by differences in age, blood pressure, heart rate, stress, type or severity of stroke. The high plasma norepinephrine in the stroke group is consistent with an increase in peripheral sympathetic activity which could produce the cardiac abnormalities of cerebral infarction.

Abnormal sympatho-adrenal function and plasma catecholamines in obese Zucker rats

The functional integrity of the peripheral sympathetic nervous system and adrenal medulla was assessed in homozygous, lean and obese, 7–8 month old male Zucker rats by the changes in plasma catecholamines during cold and immobilization stresses. Five of eight obese, but no lean rats died during a 24 hr cold stress (4–7°C) from hypothermia. While both lean and obese rats had decreased rectal temperatures after 4 hr of cold stress, the obese had lower temperatures, relatively less of an increase of plasma norepinephrine (NE) and epinephrine (E) than the lean rats, and were unable to consistently maintain their temperatures even during intravenous NE infusions. Obese rats had lower rectal temperatures and higher plasma NE and dopamine levels at 21–22°C ambient temperature, a relative failure to increase plasma NE and E levels after 1 hr of immobilization, but normal or supranormal plasma catecholamine levels after decapitation compared to the lean rats. These results suggest that the obese Zucker rat has abnormalities of both peripheral sympatho-adrenal function and thermoregulation, which may play roles in the development and/or maintenance of many of the physiological and metabolic defects in this animal model of genetic obesity.

Noradrenaline clearance in hypertensive patients with various degrees of renal function.

1. Hypertensive patients with normal renal function showed significantly higher plasma urinary noradrenaline than the normotensive controls, and the hypertensive patients with mild to moderate disturbance of renal function showed the same noradrenaline concentration as the controls. 2. Hypertensive patients with severe renal function disturbance showed significantly higher plasma noradrenaline concentrations and lower urinary noradrenaline excretion than the controls. 3. Noradrenaline clearance calculated by free plasma noradrenaline and total urinary noradrenaline was significantly decreased in those subjects with severe renal dysfunction. 4. Conjugated plasma noradrenaline was increased in the hypertensive patients with the severe disturbance of renal function, and conjugated urinary noradrenaline increased in those without severe renal dysfunction.

Elevated plasma noradrenaline concentrations in duodenal ulcer patients are not normalized by vagotomy.

Plasma noradrenaline, heart rate, and serum gastrin were significantly greater in 12 patients with duodenal ulcer compared to 12 normal subjects. Arterial blood pressure was the same in patients and controls. Intravenous infusion of adrenaline resulted in a greater rise in serum gastrin in duodenal ulcer patients, while the rise in plasma adrenaline was very similar in both groups of subjects. This suggests that the clearance of catecholamines from plasma is not retarded in duodenal ulcer patients. The abnormally high plasma noradrenaline concentrations were unchanged after vagotomy, indicating that the elevated plasma noradrenaline in duodenal ulcer patients is not related to epigastric pain. The elevated plasma noradrenaline levels in patients with duodenal ulcer are not explained by a general difference in plasma noradrenaline and sympathetic nervous activity between patients and controls because plasma noradrenaline is not elevated in other groups of patients, viz. patients with essential arterial hypertension and diabetics without ketosis and neuropathy. It may be that patients with duodenal ulcers are subject to more stress than normal subjects, provided that chronic stress does not result in arterial hypertension. It is also possible that the elevated plasma noradrenaline concentrations in these patients are compensatory to other cardiovascular changes or derived from outside the cardiovascular system, e.g. from the gastrointestinal tract. {J Clin Endocrinol Metab49: 331, 1979)

High Plasma Norepinephrine Concentrations at Birth in Infants of Diabetic Mothers

Analysis of plasma norepinephrine (NE) concentrations in umbilical artery and vein from infants of diabetic and nondiabetic mothers revealed high plasma NE values in those of diabetic mothers. While birth weight and arterial plasma NE did not correlate in infants of nondiabetic mothers (r = 0.07, NS), birth weight and plasma NE were related inversely in infants of diabetic mothers (r = -0.73, P less than 0.05).

High plasma norepinephrine concentrations at birth in infants of diabetic mothers

High plasma norepinephrine concentrations at birth in infants of diabetic mothers

Sympathetic reflex responses during treatment of essential hypertension with hydrallazine and oxprenolol.

1. The short term effects of hydrallazine, oxprenolol and oxprenolol plus hydrallazine were studied in five patients with essential hypertension. 2. The increase in pulse rate caused by hydrallazine was prevented by combined treatment with oxprenolol, which also lowered the high plasma noradrenaline levels, associated with the use of hydrallazine. 3. Plasma renin activity was higher in the supine and standing positions with hydrallazine than with oxprenolol alone and with the patients standing this high renin level was prevented by simultaneous treatment with oxprenolol. With the patients supine, combination of oxprenolol with hydrallazine resulted in a mean plasma renin activity which was less than half that with hydrallazine alone, although this difference was not statistically significant. 4. The combination of oxprenolol with hydrallazine did not lower the blood pressure further, but reduced the increased sympathetic activity which occurred with hydrallazine alone.

Ethnic Differences in Blood Pressure with Observations on Noradrenaline and Renin. 2. A Hospital Hypertensive Population

100 patients with essential hypertension (77 whites, 23 black) were studied with measurements of plasma noradrenaline concentration and plasma renin activity. Black patients had higher blood pressure than whites. There were no ethnic differences in mean plasma noradrenaline, but plasma renin activity was lower in blacks than whites, and this difference was not related to differences in sodium intake. Plasma noradrenaline increased with age in blacks, and in a white control group. Young white hypertensive patients (< 45 years) had higher plasma noradrenaline than controls, and in white hypertensives plasma noradrenaline was positively correlated with plasma renin.

Plasma Noradrenaline Concentrations and Haemodynamics in the Early Stage of Essential Hypertension

1. Plasma noradrenaline concentrations and haemodynamic status were simultaneously studied in young patients with uncomplicated essential hypertension and in age-matched normal controls. 2. Resting plasma noradrenaline in the controls tended to increase slightly, but progressively, with age. The hypertensive subjects had significantly higher plasma noradrenaline concentrations than those in the controls, but these values did not show any age-related variation. The response of plasma noradrenaline to the standing position tended to increase with age in the controls, whereas plasma noradrenaline in the hypertensive subjects showed a wide range of responses without any fixed relationship with age. 3. The cardiac index was significantly greater in the labile hypertensive subjects than in the controls, whereas total peripheral resistance was significantly greater in the sustained hypertensive subjects than in the labile patients and in the controls. Mean arterial pressure in these patients was closely related with the value of total peripheral resistance rather than with the cardiac index. 4. Of the patients with raised plasma noradrenaline 80% showed significantly increased values of either total peripheral resistance or cardiac index. Plasma noradrenaline was correlated significantly to total peripheral resistance, and marginally to mean arterial pressure. 5. These findings support the view that sympathetic nervous overactivity is an important factor underlying the haemodynamic findings in these patients.

Effect of labetalol on plasma noradrenaline and adrenaline in hypertensive man

Injection i.v. of labetalol, a new adrenergic alpha- and beta-blocking agent, decreased arterial blood pressure in 9 hypertensive subjects resting in the supine position, when standing and during supine exercise. Heart rate after labetalol was unchanged in the resting supine position, and it fell in the latter two conditions. Plasma noradrenaline concentration was higher after labetalol in all three experiments as compared to a control study. Plasma adrenaline after labetalol was increased only in the standing position, when the highest plasma noradrenaline concentrations were observed. Blood glucose concentration tended to increase after labetalol, but the difference was not statistically significant. The changes in plasma noradrenaline and blood glucose after labetalol mimic findings observed after alpha-adrenergic receptor blockade. The beta-adrenergic receptor blocking property of labetalol is responsible for the reduced heart rate and it is likely to contribute to the higher plasma noradrenaline concentration observed when standing and during supine exercise.

Plasma catecholamines and carbohydrate metabolism in patients with acute myocardial infarction.

Blood glucose, glucose tolerance, serum insulin, free fatty acids in serum, plasma noradrenaline, and plasma adrenaline were measured in 10 patients with acute myocardial infarction (AMI) as well as in healthy subjects. Both noradrenaline and adrenaline in plasma were elevated in patients with AMI, the level being fairly constant in the individual patients and dependent on their degree of illness. In the fasting state, blood glucose, serum insulin, and free fatty acids were elevated in patients with AMI. Plasma noradrenaline showed a highly significant correlation with the fasting blood glucose concentration, but not with serum insulin or free fatty acids. The concentration of free fatty acids in serum could be predicted only if both plasma noradrenaline and the basal insulin concentration were known. Intravenous glucose tolerance was reduced in patients with AMI, especially in patients with high plasma noradrenaline and a low initial rise in insulin. There was a significant negative correlation between the initial rise in insulin expressed in percentage of the basal insulin concentration and the plasma noradrenaline level. The statistical effects of serum insulin and plasma noradrenaline on the glucose tolerance could not be separated from each other. The decline in free fatty acids after intravenous injection of glucose showed a negative correlation with plasma noradrenaline and a positive correlation with the initial rise in insulin. Plasma adrenaline did not correlate with any of the metabolic parameters mentioned above. The plasma noradrenaline concentration was elevated to such a degree in patients with AMI that the observed changes in metabolism might have been caused directly by the circulating noradrenaline. During the glucose tolerance tests, the effects of noradrenaline was probably carried out indirectly via a suppression of insulin secretion. It is conceivable that any effect of plasma noradrenaline on the basal insulin secretion was neutralized by the fasting hyperglycemia.