Salivary Electrolytes in Treated Hypertensives at Low or Normal Sodium Diet

The aim of this study was to investigate possible abnormalities in salivary electrolytes in hypertensives treated with ace-inhibitors (ACE-I) or calcium antagonists (Ca-ANT) at low or normal sodium intake. Hypertensives treated with ACE-I (n.14) or Ca-ANT (n.22) and 13 normotensives were studied during normal or restricted Na intake. Na, K, Ca, Mg and Cl were determined in saliva samples collected by using a standardized adsorption procedure (SALIVETTE). Na intake was evaluated by determination of the 24-hr urinary Na excretion. Similar concentrations of Na, K, Ca, and Cl were found in normotensives and in hypertensives treated with ACEI or Ca-ANT both at low or normal Na diet. Magnesium in saliva appeared reduced in ACEI-treated hypertensives (0.28 ±0.06 mmol/1) in comparison to the similar values of normotensives (0.53 ± 0.05) and Ca-ANT treated hypertensives (0.54 ± 0.07). In normotensives and in treated hypertensives lowring of Na intake did not change the salivary content of Ca, Mg and Cl but produced in saliva a reduction of Na associated to a rise in K. salivary Na/K ratio was significantly correlated with 24 hr urinary Na excretion in normotensives (r = 0.77; p < 0.05) and in hypertensives treated with ACE-I (r = 0.74; p < 0.0 5) or Ca-ANT (r = 0.62; p < 0.05). The low salivary magnesium in ACE-I-HT may have a role in the occasional ACEI-dependent dysgeusia. Salivary Na/K ratio may be used as a rough index of Na intake in treated hypertensives.     

Vasopressor and Vasodepressor Hormone-Systems in Adolescent Hypertension

We investigated the activity of the renin-angiotensin-aldosterone-system, the secretion of catecholamines and the kallikrein-kinin-system in 126 adolescents randomly selected from a large study of 1342 young people examined in an epidemiological survey conducted in Cologne in 1975, 1976 and 1980. 73 of them with arterial blood pressures below 145/90 mm Hg were called “normotensives” (systolic blood pressure 127.2 ± 1.0 mm Hg, diastolic bp 79.7 ± 0.8 mm Hg). They were compared with 53 “hypertensives” (systolic blood pressure 147.2 ± 1.6 mm Hg, diastolic bp 93.7 ± 1.1 mm Hg).

Urinary catecholamines were significantly higher in the hypertensives (155.0 ± 13.3 μg/d) compared to the normotensives (100.7 ± 5.3 μg/d) (p < 0.001) whereas plasma levels of adrenaline and noradrenaline were similar. Serum aldosterone levels and plasmarenin-concentrations were not different between the two groups. Angiotensin-converting-enzyme-activity was slightly higher in the hypertensive group (107.1 ± 3.5 U/1 versus 98.0 ± 2.6 U/1, p < 0.001). Urinary kallikrein excretion was found to be modestly lower in hypertensives compared to normotensives (0.40 ± 0.05 versus 0.55 ± 0.06 mU/mg creatinine). Urinary excretion of sodium and potassium, blood levels of glucose, uric acid, cholesterol and triglycerides were similar in both groups. The results of the present study suggest an increased sympathetic activity in the early stage of hypertension in adolescents.     

Significance of the Measurement of Urinary Alanine Aminopeptidase and N-Acetyl-β-D-Glucosaminidase Activity in Evaluating Patients with Essential Hypertension

To examine the relationship between the urinary levels of alanine aminopeptidase (AAP) or N-acetyl-β-D-glucosaminidase (NAG) and the advance of essential hypertension, we measured the urinary levels of these enzymes in 20 normotensive controls, 8 subjects with borderline hypertension and 40 subjects with WHO stage I and stage II essential hypertension. The urinary level of NAG in stage II hypertensives was higher than that in the normotensives, and borderline or stage I hypertensives (p < 0.01). Systolic blood pressure and the urinary level of NAG was positively correlated in hypertensives (rs=0.43, p < 0.01). The urinary level of NAG was correlated inversely with renal blood flow (rs=-0.61, p < 0.01). The urinary level of AAP in stage II hypertensives was also higher than that in the normotensives (p < 0.01) or stage I hypertension (p < 0.01), but the urinary AAP level was not significantly correlated with systolic blood pressure or renal blood flow in hypertension.     

Handgrip Increases Endothelin-1 Secretion in Normotensive Young Male Offspring of Hypertensive Parents

Objectives. We tested the hypothesis that an abnormal response of plasma endothelin-1 (ET-1) is elicited by handgrip exercise (HG) in young normotensive offspring of hypertensive parents.Background. It has been hypothesized that ET-1 is involved in blood pressure control and plays a pathophysiologic role in the development of clinical hypertension.Methods. Two groups of healthy male subjects, 11 with hypertensive parents (group A) and 10 without a family history of hypertension (group B), underwent 4 min of HG at 50% maximal capacity. Heart rate and blood pressure and plasma levels of ET-1, epinephrine and norepinephrine were measured at baseline, peak HG, and after 2 (R2) and 10 (R10) min of recovery.Results. Group A had higher norepinephrine levels than group B throughout the test (baseline 181 ± 32 [SEM] vs. 96 ± 12 pg/ml, p < 0.05; peak HG 467 ± 45 vs. 158 ± 12 pg/ml, p < 0.000001; R2 293 ± 46 vs. 134 ± 8 pg/ml, p < 0.01; R10 214 ± 27 vs. 129 ± 10 pg/ml, p < 0.0005); no significant difference in epinephrine levels was detected. Compared with group B subjects, group A had higher baseline ET-1 levels (1.07 ± 0.14 vs. 0.59 ± 0.11 pg/ml, p < 0.02), which increased to a greater extent at peak HG (1.88 ± 0.31 vs. 0.76 ± 0.09 pg/ml, p < 0.005) and R2 (2.46 ± 0.57 vs. 1.31 ± 0.23 pg/ml, p < 0.05) and remained elevated at R10 (3.16 ± 0.78 vs. 0.52 ± 0.09 pg/ml, p < 0.002). Multivariate analysis demonstrated that only a family history of hypertension (chi-square = 7.59, p = 0.0059) and ET-1 changes during HG (chi-square = 4.23, p = 0.0398) were predictive of blood pressure response to HG and that epinephrine and norepinephrine were not.Conclusions. The response to HG in offspring of hypertensive parents produced increased ET-1 plasma levels and resulted in a sustained ET-1 release into the bloodstream during recovery compared with offspring of normotensive parents. This may be an important marker for future clinical hypertension.     

Atrial Natriuretic Factor Response to Acute Volume Expansion in Borderline Hypertension. Role of Ace-Inhibition and Changes in Peripheral Venous Tone

Abnormalities in the response of atrial natriuretic factor (ANF) to volume expansion have been reported in hypertensive-prone animals and men as well as in hypertensive patients undergoing ACE-inhibition. To investigate some of the mechanisms affecting ANF release in borderline hypertensive patients (BHT) we have studied 16 subjects by assessing their neuro-humoral and hemodynamic response to a two-hour isotonic i.v. NaCl infusion carried out during short-term administration of either placebo or captopril. ACE-inhibition increased baseline venous distensibility (VV₃₀:1.4 vs 1.6 ml/100 ml;p<.05) and reduced the prompt (45′) ANF response to saline loading (10.3±13 vs 42.7±15%;p<.05)) without affecting the overall ANF release (120′:92±25 vs 65.8±20%;NS)). A significant pressor increase in response to NaCl loading was observed exclusively after ACE-inhibition (SBP:5.2±2 vs 2.4±1%; p < .05 - DBP:7.1±3 vs 2±3%; p < .025) and occurred along with a peripheral arterial and venous constriction and with an increase in plasma levels of an endogeneous Na⁺/K⁺ ATPase inhibitor (8.8 ± 4 vs ?2±4%; p <.05). We conclude that the ANF response to saline infusion is delayed by ACE-inhibition in borderline hypertensives. The abnormalities observed in ANF response could follow the changes in peripheral venous distensibility and contribute to the pressor and neuro-humoral derangements described in borderline hypertensives during volume expansion.     

Enhanced red cell sodium permeability in patients with borderline hypertension

Red cell membrane sodium permeability was studied in 41 untreated patients with essential hypertension (20 borderline hypertensives and 21 established hypertensives) and 21 age matched normotensive subjects by means of the measurement of unidirectional passive influx of 22Na+ into ouabain-treated erythrocytes. The mean value (+/- SD) of 22Na+ influx was greater in the hypertensives than in the normotensives (0.183 +/- 0.047 vs 0.152 +/- 0.047 mmol/l . cells/hr, respectively, p less than 0.02). Among the patients with essential hypertension, the borderline hypertensives demonstrated a higher 22Na+ influx than the established hypertensives (0.207 +/- 0.043 vs 0.160 +/- 0.038 mmol/l . cells/hr, respectively, p less than 0.001), and 22Na+ influx positively correlated with plasma renin activity (r = 0.44, p less than 0.005). In 16 of 20 borderline hypertensives, 5 year blood pressure changes were examined retrospectively, and a positive correlation was observed between mean blood pressure increase and 22Na+ influx value in these subjects (r = 0.64, p less than 0.01). These results suggest that passive sodium influx may be altered in the course of the development of hypertension in relation to the changes in blood pressure level and that enhanced sodium permeability may be a characteristic of the early stage of essential hypertension.     

The Relationship of Lithium-Potassium Cotransport and the Passive Lithium Leak to Hypertension in Utah Subjects

Rate constants for lithium-potassium cotransport (k_LPC) and the lithium efflux into MgCl₂ with furosemide (passive lithium leak) along with sodium-lithium countertransport (SLC) were measured in erythrocytes from 351 normotensive adults age 18 and over, 220 youth under age 18 and in 27 hypertensives. The k_LPC was significantly higher in the hypertensives than the adult normotensives with means and standard deviations of 13.9 ± 9.2 vs. 8.7 ± 5.9 10^?3/hr (p < 0.01). Adjusting for the significant weight (p = 0.014) and sex (p = 0.066, normotensive males higher than females) associations with k_LPC in an analysis of covariance, increased the significant difference between the hypertensives and normotensives (p = 0.0004). The passive lithium leak rate constant was also higher in hypertensives than normotensives (20.2 ± 7.6 vs. 15.5 ± 5.3 10^?3/hr, p < 0.01). Weight (p=0.0003), but not sex, was related to the leak but did not account for the difference between hypertensives and normotensives (p = 0.0009). Mean blood pressure was positively associated with the lithium leak but not the k_LPC or SLC values in a multivariate regression.     

Vascular Hypertrophy in Borderline Hypertension: Relationship to Blood Pressure and Sympathetic Drive

While borderline hypertension increases the chance for cardiovascular disease, most with borderline hypertension will not experience problems. Thus, the risk of intervening probably outweighs benefit for the majority. However, those with target organ damage are probably at higher risk and might benefit from more aggressive management. Therefore, we assessed vascular hypertrophy and average home blood pressures in patients with borderline hypertension which might be of value in therapeutic planning.

Minimum forearm vascular resistance (mFAVR) was used as an index of vascular hypertrophy. Comparing ten normotensive controls to twenty individuals with borderline hypertension revealed a significant difference in mFAVR (1.7 0.06 vs 2.1 0.1, p<.05). There were obvious differences in blood pressure between normotensives and borderlines which contributed to differences in mFAVR. However, within the group with borderline hypertension, no relationship was apparent between mean blood pressure and mFAVR, r=0.13, NS. Among the borderline hypertensives, baseline plasma norepinephrine correlated with mFAVR, r=0.48, p<.05, suggesting that the sympathetic nervous system contributes to vascular hypertrophy in this group.

In a separate group of individuals with nine normotensives and nine borderline hypertensives we wished to find if average home blood pressure would correlate better with mFAVR than a single laboratory measurement. While both the home (r=0.56, page missing 244     

Serial plasma catecholamine response early in the course of clinical acute myocardial infarction: Relationship to infarct extent and mortality

Clinical and experimental evidence suggest that sympathoadrenal activation contributes to mortality in patients with ischemic heart disease. To determine the level of sympathoadrenal activation in the very early phase of acute myocardial infarction (AMI) and to determine if location of infarction (anterior versus inferior) was related to sympathoadrenal activation, we studied norepinephrine (NE) and epinephrine (E) within 4 hours after the onset of symptoms and prior to any rise in plasma creatine kinase (CK). Mean (± SE) initial (NE = 591 ± 111 pg/ml and E = 73 ± 19 pg/ml), peak (NE = 1356 ± 178 and E ± 1098 ± 608) and average (NE = 815 ± 142 and E = 252 ± 68) plasma catecholamine concentrations were considerbly above normal (NE = 228 ± 10 and E = 34 ± 2 pg/ml, n 60) and values were similar for inferior and anterior infarctions. During an 18-month follow-up, three patients died in whom the AMI mean NE and E and peak CK were higher than in the eight late survivors. Thus the three AMI patients with peak EP values > 1000 died, whereas the eight AMI patients with peak EP values < 1000 survived (p < 0.01). The magnitude of sympathoadrenal activation early in the course of clinical AMI appeared related to the extent of myocardial damage and late mortality.     

Arterial and coronary sinus catecholamines in the course of spontaneous coronary artery spasm

We studied plasma catecholamine levels in 10 patients with frequent spontaneous episodes of coronary artery spasm to evaluate the role of the sympathetic nervous system. Peripheral venous norepinephrine in supine and upright postures, urinary excretion of catecholamines, and functional testing of the sympathetic nervous system did not differ from the same measurements in control subjects. Arterial and coronary sinus levels of norepinephrine and epinephrine drawn early in ischemia were not elevated over baseline; coronary sinus norepinephrine levels were higher than those in arterial samples and rose from 315 ± 32 (pg/ml ± SE) at the onset of ST elevation to 490 ± 49 pg/ml late in ischemia (p < 0.05). Plasma epinephrine levels, higher in arterial than coronary sinus samples, also rose significantly only late in ischemia, from 44 ± 14 pg/ml to 148 ± 35 pg/ml (p < 0.05) in arterial blood and from 33 ± 10 pg/ml to 108 ± 29 pg/ml in coronary sinus samples (p < 0.05). Generalized sympathetic nervous system activation is not likely to be the sole cause of coronary artery spasm.     

Left ventricular wall thickness and plasma catecholamines in borderline and stable essential hypertension

It has been suggested that sympathetic overactivity has a pathogeneticrelevance to left ventricular hypertrophic development, evenapart from its effect on and in essential hypertension. To evaluate this possibility by echocardiographic and polygraphicmethods, we studied left ventricular wall thickness and functionand their possible relationship to plasma renin activity andplasma catecholamines in 11 normal subjects, 13 borderline hypertensivesand 11 stable hypertensives without radiological or electrocardiographicsigns of left ventricular hypertrophy. Compared with normal, borderline hypertensives showed an increasein interventricular septum (IVS) thickness (P < 0.01) andIVS/posterior wall (PW) thickness ratio (P < 0.01) togetherwith an increased supine and upright plasma norepinephrine (NE;P < 0.01); there was also a decreased pre-ejection period(PEP; P < 0.01), PEP/left ventricular ejection time ratio(P < 0.01) and total electromechanical systole (P < 0.05). In stable hypertensives, PW thickness was greater than it wasboth in normals (P < 0.01) and in borderline hypertensives(P < 0.01) and IVS thickness was higher than in normals (P< 0.05). Positive correlations between supine (P < 0.001), upright(P < 0.05) NE and both IVS thickness and IVS/PW thicknessratio were found in borderline but not in stable hypertensives. These results support the hypothesis recently put forward thatIVS hypertrophy may represent an early stage of essential hypertension-inducedLVH, which afterwards extends to the left PW; furthermore theresults suggest that the sympathetic overactivity may play arole in the IVS hypertrophy development in borderline hypertensives.     

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)     

Effect of tyramine on myocardial catecholamine release in coronary heart disease

The influence of tyramine on myocardial catecholamine release and on coronary blood flow has not previously been determined in man. Therefore, the effect of tyramine was measured on coronary and systemic hemodynamics and on norepinephrine (NE) and epinephrine levels in blood from the aorta and coronary sinus in 9 patients with coronary artery disease. Tyramine produced a striking increase in coronary sinus NE, from a baseline of 344 ± 56 to a peak level of 1416 ± 310 pg/ml (p < 0.01) 2 minutes after tyramine. The increase in aortic NE was less striking, from 265 ± 32 to 421 ± 63 pg/ml (difference not significant). Therefore, the net release of NE from the heart was increased by tyramine from 12,007 ± 393 to 139,357 ± 46,156 pg/ ml/min (p < 0.03). There was no release of epinephrine across the coronary bed. There was a variable response of coronary blood flow and resistance after tyramine. Thus, the rich innervation of the heart by sympathetic nerve endings can result in marked NE release into the coronary sinus.     

Early impairment of coronary flow reserve in young men with borderline hypertension

Objectives. The purpose of this study was to investigate whether functional abnormalities in coronary vasomotion are present in young healthy asymptomatic men fulfilling the World Health Organization (WHO) criteria for borderline hypertension.Background. Previous studies have reported reduced coronary flow reserve in middle-aged subjects with sustained hypertension and hypertension-induced microvascular heart disease or left ventricular hypertrophy.Methods. Myocardial blood flow was measured at baseline and during dipyridamole-induced hyperemia by means of positron emission tomography and oxygen-15–labeled water in asymptomatic young men with borderline hypertension (group 1: n = 16, mean ± SD age 37 ± 4 years, 24-h ambulatory blood pressure 135 ± 10/81 ± 9 mm Hg) and matched healthy control subjects (group 2: n = 19, age 35 ± 3 years, 24-h ambulatory blood pressure 119 ± 8/69 ± 8 mm Hg, p < 0.001). Left ventricular (LV) mass, dimensions and function were measured by echocardiography.Results. LV mass, dimensions and diastolic function were similar in the study groups. Baseline myocardial blood flow was similar (0.83 ± 0.21 vs. 0.80 ± 0.22 ml/g per min, group 1 vs. group 2, respectively, p = NS), and a significant increase in flow was detected after dipyridamole infusion (0.56 mg/kg body weight in 4 min intravenously) in both groups. However, the flow response to dipyridamole was significantly lower in group 1, leading to lower hyperemic flow in group 1 than in group 2 (2.85 ± 1.20 vs. 3.80 ± 1.44 ml/g per min, respectively). Consequently, the coronary flow response was lower in hypertensive than in normotensive men (3.46 ± 1.23 vs. 4.99 ± 2.5 ml/g per min, group 1 vs. group 2, respectively, p < 0.05).Conclusions. These results demonstrate reduced coronary reactivity present in young asymptomatic men with borderline hypertension and no signs of hypertension-induced angina or left ventricular hypertrophy. Because baseline basal myocardial blood flow was unchanged, the reduction in coronary flow reserve depends on an impaired maximal vasodilator capacity.     

Increased Sodium Influx into Erythrocytes in Diabetes Mellitus and Hypertension

A variety of abnormality has been reported in the cation transport systems in erythrocytes in essential hypertension. To determine the existence of similar abnormality in diabetics with hypertension, sodium (Na+) influx into erythrocytes in the presence of ouabain (measured by using 22Na+), and the Na+ and potassium (K+) content in intact erythrocytes were examined. Subjects, all of whom were Japanese, were divided into 4 groups; 23 nondiabetic, normotensive control subjects without family history of hypertension (control group), 20 patients with essential hypertension (group 1), 21 normotensive diabetics without family history of hypertension (group 2) and 15 hypertensive diabetics (group 3). Na+-K+ pump activity (measured by using 86Rb+) was studied in some of them, too. Na+ influx in group 1 was 0.451±0.111 m mol/Kg erythrocytes/h, significantly more elevated than that in the control group (0.345±0.080, p < 0.001). Na+ influx in group 2(0.435±0.094) was significantly greater than that in the control group(p < 0.005), but no significant difference was found between groups 1 and 2. Na+ influx in group 3 (0.551±0.128) was significantly higher than that in the control group (p < 0.001), in group 1(p < 0.02), or in group 2(p < 0.005). There were no significant differences in Na+-K+ pump activity, or Na+ and K+ content among the 4 groups. These findings suggested that: 1) Na+ influx into ouabain-treated erythrocytes was higher in patients with essential hypertension than in control subjects in Japanese, 2) diabetes mellitus per se might increase Na+ influx, and 3) the elevation of blood pressure in hypertensive diabetics as well as in essential hypertensives might be related to the increased Na+ influx.     

Sympathoadrenal Responses to Stress: The Linking of Type a Behavior Pattern to Ischemic Heart Disease

This report is an analysis of the findings of blood pressure, pulse rate, adrenergic and noradrenergic responses to laboratory and clinical stresses in subjects according to Type. A and Type B behavior patterns. Thirty-three experiments of Type A B cardiovascular and sympathcadrenal responses to a variety of laboratory stressors were identified. Twenty-nine of these were analyzed and the data of 20 were pooled to give mean values for the percentage increments of systolic and diastolic blood pressures, pulse rates, and plasma levels of NE and E for Type A vs B patients respectively; (15 ± 2 vs 10 ± 1, P <.05; 13 ± 1 vs 8 ± 1, P <.02; 19 ± 2 vs 13 ± 2, P <.05, 60 ± 11 vs 19 ± 8, P <.02; and 106 ± 45 vs 23 ± 12, P <.1). Seventy-five percent of the analyzed experiments provided evidence for heightened cardiovascular and sympathoadrenal responsivity in Type A subjects. NE and E appear to be hormonal Intermediates which play a lethal role in ischemlc heart disease. Neutralization of neural tone may be an important goal in the therapy of hypertensives with Type A behavior pattern.     

Arterial baroreflex sensitivity, plasma catecholamines, and pressor responsiveness in essential hypertension

Arterial baroreflex sensitivity, plasma norepinephrine (NE) and epinephrine (E), and pressor and depressor responses were assessed in 25 patients with essential hypertension and 29 normotensive control subjects. Sensitivity of the cardiac limb of the baroreflex was determined by blood pressure and interbeat interval responses associated with the Valsalva maneuver, externally applied neck suction and pressure, and injection of phenylephrine and nitroglycerin. By all these techniques, patients with essential hypertension had significantly decreased baroreflex sensitivity, even after adjustment for age mismatching between the hypertensive and normotensive groups. Hypertensive patients also had significantly higher mean levels of plasma NE and E in both brachial arterial and antecubital venous blood (246 vs 154 pg/ml arterial NE, 286 vs 184 pg/ml venous NE, 99 vs 55 pg/ml arterial E, and 65 vs 35 pg/ml venous E) and significantly larger pressor responses to injected phenylephrine (30.9 mm Hg/100 micrograms vs 16.7 mm Hg/100 micrograms). When baroreflex-cardiac sensitivity values measured by the various techniques were averaged, there was a significant inverse relationship between sensitivity and venous NE and between sensitivity and pressor responsiveness. The results indicate that decreased baroreflex-cardiac sensitivity, increased sympathetic outflow, and pressor hyperresponsiveness tend to occur together in some patients with essential hypertension. Decreased arterial distensibility and altered central neural integration can account for these findings.     

Do screening blood pressure and plasma catecholamines predict development of hypertension? Twenty-year follow-up of middle-aged men

OBJECTIVES: The sympathetic nervous system is implicated in the development and maintenance of hypertension. However, the predictive impact of arterial plasma catecholamines has never been reported. We investigated arterial catecholamines and blood pressures (BPs) prospectively over 20 years in a group of well-characterized middle-aged men. METHODS: Fifty-six of original 79 men were available for the follow-up. Multiple regression analysis was done with mean BP at follow-up as a dependent variable, and arterial plasma catecholamines and BP at baseline as independent variables. RESULTS: Half of the originally normotensive men developed hypertension during follow-up. There were significant differences in the screening BP values measured at baseline between the new hypertensives and the sustained normotensives. Multiple regression analysis revealed arterial adrenaline at baseline as an independent predictor of mean BP at follow-up in the new hypertensives (beta = 0.646, R2 = 0.42, p = 0.007). Furthermore, arterial noradrenaline at baseline was a negative independent predictor of mean BP at follow-up in the sustained normotensives (beta = -0.578, R2 = 0.334, p = 0.020). Noradrenaline increased with age in the group as a whole (1318+/-373 vs 1534+/-505 pmol/l, p = 0.010) while adrenaline did not change. CONCLUSION: Our data suggest that arterial adrenaline is involved in the development of hypertension over 20 years in middle-aged men. Men with sustained normotension may have an inherent protection against sympathetic overactivity. Furthermore, screening BP at baseline in normotensive men differentiated between those who developed hypertension and those who remained normotensive at follow-up.     

Dopaminergic modulation of pressor and hormonal responses in essential hypertension

Hormonal and mean arterial pressure (MAP) responses to posture, isometric handgrip, angiotensin II (AII), adrenocorticotrophic hormone (ACTH), and metoclopramide (MCP), a dopamine (DA) antagonist, were examined in nine men with essential hypertension and nine age- and weight-matched normotensive men on a constant 100 mEq sodium and 80 mEq potassium intake before and after 4 days of administration of the DA agonist, bromocriptine (BEC; 2.5 mg three times a day). BEC depressed supine basal MAP in the hypertensives, and decreased MAP response to posture and isometric exercise in both groups. Hypertensives displayed greater (p less than 0.01) NE responses to posture and exercise than the normotensives. BEC decreased the NE response to 10 minutes of upright posture and exercise more in hypertensives (p less than 0.01) than in normotensives, but following BEC, the responses were similar. BEC did not affect basal PRA or PRA responses to posture and exercise in the two groups. PA responses to ACTH and MCP were similar in both groups, but the hypertensives displayed greater (p less than 0.01) PA responses to AII. BEC suppressed PA responses to AII (p less than 0.01) and to high dose ACTH (p less than 0.05) to a similar extent in both groups. The prolactin as well as the PA response to DA antagonism with MCP was similar in the two groups. These results suggest that dopaminergic control of NE secretion may be altered in essential hypertension. Blood pressure lowering effects of BEC in patients with essential hypertension may be related, in part, to depression of sympathetic nervous system activity.     

Relationship Between Plasma Catecholamines and the Renin-Aldosterone System During Exercise in Normal and Essential Hypertensive Subjects

Interrelations were investigated between blood pressure, plasma epinephrine (E), norepinephrine (NE), dopamine (D), aldosterone, cortisol concentrations, active and inactive plasma renin activity (PRA), and age in 21 normotensive subjects (aged 20–60 years) and in 25 patients (aged 20–63 years) with essential hypertension (EH). These parameters were measured at rest and during exercise on a bicycle ergometer. In normotensive subjects basal and exercise-stimulated levels of plasma NE increased with age which was not observed in EH. In hypertensive patients there was a higher plasma D concentration under the exercise as compared with normotensive controls. In the normotensives, basal active PRA was inversely related to age (p<0.05), and during initial 8 min of exercise active PRA significantly correlated with plasma E and plasma NE. Moreover, absolute changes from basal to acutely stimulated values of active PRA were directly related to the changes of plasma E and NE (p<0.001). In hypertensive patients these relationships were not found. However, in the hypertensives there were significant positive correlations between the increases of active PRA, plasma E, plasma NE on the one hand and their respective basal values on the other hand.

The results indicate very strong functional relationship between the sympathetic-adrenomedullary and renin-angiotensin systems during initial interval of acute stimulation in normotensive subjects. Essential hypertension is not a pathophysiologically homogenous disease with respect to reactivity and interaction of plasma catecholamines and PRA. Separate regulatory pathways exist for plasma active and inactive renin. During short-time exercise aldosterone secretion is related rather to the renin-angiotensin system than to the hypothalamic-pituitary axis.