Sodium depletion increases platelet and plasma catecholamines in hypertensive men.

The catecholamine content in blood platelets is considerably higher than that in plasma, and platelet catecholamines must be taken up from plasma, since blood platelets lack enzymes for catecholamine synthesis. However, it is unknown whether platelets take up and store catecholamines during physiological in vivo increments in plasma catecholamines. Previously untreated 50-year-old men (n = 17) with mild to moderate essential hypertension were given a low sodium diet for 2 weeks. Urinary excretion of sodium decreased from 201 +/- 11 (SE) to 24 +/- 5 and 19 +/- 4 mmol/24 hr after 1 and 2 weeks, respectively. During the first week, the blood platelet concentration of norepinephrine increased from 27.2 +/- 2.9 to 39.6 +/- 4.7 pg/mg (p less than 0.005) and venous plasma norepinephrine increased from 3.7 +/- 0.4 to 5.6 +/- 0.5 pg/ml (p less than 0.005), and venous plasma dopamine increased from 26 +/- 4 to 41 +/- 5 pg/ml (p less than 0.05). During the second week, both plasma and platelet norepinephrine and dopamine remained elevated. Platelet epinephrine showed a small increase from baseline to the second week (p less than 0.05), but no concomitant increase in plasma epinephrine occurred. Thus, sodium depletion increases both platelet and plasma catecholamines and blood platelets may take up catecholamines in vivo. Platelet catecholamine content may be an integrated measure of plasma catecholamine concentrations during variations caused by sodium depletion.

Increased plasma vasopressin in low renin essential hypertension.

Baseline plasma vasopressin concentrations were measured in 48 men (all 50 years old) with decreased plasma renin concentration and untreated, sustained essential hypertension and in 29 healthy normotensive men. Mean hypertensive plasma vasopressin concentration was more than twice as high as the corresponding normotensive level (15.7 +/- 2.2 [SE] vs 7.5 +/- 1.0 pg/ml; p less than 0.001). Plasma renin concentration in the hypertensive group was reduced compared with that in the normotensive group (0.28 +/- 0.04 vs 0.46 +/- 0.06 Goldblatt units X 10(-4)/ml). These differences appeared despite virtually identical serum osmolality, creatinine clearance, and urinary sodium excretion in the two groups. In the first 38 hypertensive subjects, arterial plasma epinephrine concentrations were significantly increased over those of the first 28 control subjects (99 +/- 12 vs 68 +/- 6 pg/ml; p less than 0.025). In contrast to those with low renin essential hypertension, 35 men with normal renin essential hypertension (all 40 years old) had normal plasma vasopressin levels that were not significantly different from those in a comparable normotensive control group (3.7 +/- 0.8 vs 3.5 +/- 0.4 pg/ml). Arterial epinephrine concentrations were not significantly different between normal renin subjects and the control group. After 6 weeks of treatment with the nonselective beta-adrenergic receptor blocker oxprenolol in 11 subjects with low renin hypertension, blood pressure was reduced and the plasma vasopressin concentration fell from 27.6 +/- 6.4 to 13.5 +/- 4.2 pg/ml (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of beta 1- and beta 2-blockade on blood pressure and sympathetic responses to flight phobia stress.

Cardiovascular and sympathoadrenal effects of short-term oral treatment with beta 1-blockade (atenolol, 50 mg, administered two times) and beta 2-blockade (ICI 118,551, 50 mg, administered three times) were compared with placebo during actual flying in subjects with flight phobia (n = 34). beta 1-Blockade lowered resting blood pressure and heart rate and prevented a heart rate response but not a blood pressure response to this psychologic stress. beta 2-Blockade minimally lowered resting heart rate and prevented a heart rate response, but it failed to lower resting blood pressure or blood pressure response to the stress. Plasma epinephrine increased with all three treatments and more with beta 1-blockade than with placebo. Plasma norepinephrine decreased with administration of beta 2-blockade. Thus neither beta 1- nor beta 2-blockade prevents an increase in blood pressure during acute flight phobia stress. Increased plasma epinephrine seems to be the sympathetic variable that is closest related to this increase in blood pressure. Norepinephrine may be less consistently related to the blood pressure rise during flight phobia stress as shown by the decrease in plasma norepinephrine with administration of beta 2-blockade.

Decreased platelet-free dopamine and unchanged noradrenaline and adrenaline in essential hypertension.

The content of free-catecholamines in blood platelets is much higher than in plasma and platelet catecholamines must be taken up from plasma, since platelets lack the enzymes for catecholamine synthesis. There is some evidence that platelet catecholamine content under certain circumstances may be an integrated measure of plasma catecholamine concentrations over time. Platelet-free catecholamines were therefore assayed in 18 untreated patients with essential hypertension and in 16 normotensive control subjects. Mean platelet-free dopamine in the hypertensive group was 3.7 +/- 0.4 pg/mg platelet weight, i.e. significantly less than the 6.5 +/- 0.9 pg/mg found in the normotensive (p less than 0.005). Platelet contents of noradrenaline and adrenaline did not differ. Decreased platelet-free dopamine and unchanged platelet noradrenaline and adrenaline persisted after adjustment for increased body weight in the hypertensive group. Although the reasons for decreased platelet-free dopamine in the hypertensive group remain unknown, this finding may add to previous result showing facilitated release of granular contents from blood platelets in patients with essential hypertension. Our data do not support platelet levels of free-catecholamines to be a marker of increased sympathetic tone in essential hypertension.

Awareness of hypertension increases blood pressure and sympathetic responses to cold pressor test.

The present study was aimed at examining the effects of awareness of hypertension on blood pressure and sympathetic responses to the cold pressor test. Nineteen-year-old men with similarly elevated mean blood pressure at a medical screening, but without knowledge of this, were randomized into two groups. The first group (n = 16) was sent a letter saying that their pressure was too high, and the second (n = 13) was sent a neutral letter. Information increased mean blood pressure both after 15 min sitting, by an average of 11.5 mm Hg (P less than .01), and after 30 min supine rest, by an average of 4.5 mm Hg (P less than .05). Changes in heart rate (8.4 +/- 2.4 v 1.9 +/- 1.7 beats/min) and plasma epinephrine (0.11 +/- 0.04 v 0.01 +/- 0.03 nmol/L) during execution of a cold pressor test were significantly greater in the informed group (P less than .05). Plasma dopamine was lower in the informed group (P less than .05). Thus, psychological stress caused by the awareness of hypertension may increase blood pressure and sympathetic responses to a provocative maneuver. Ideally, studies on sympathetic function in essential hypertension should be undertaken on subjects unaware of their blood pressure status.

Decreased serum phosphate in essential hypertension. Related to increased sympathetic tone.

Forty-year old men with untreated mild essential hypertension (n = 35) had decreased serum phosphate (P less than 0.001) concomitant with elevated resting plasma epinephrine (P less than 0.05) and heart rate (P less than 0.001) compared with age-matched, normotensive control men (n = 44). Blood pressure correlated negatively with serum phosphate (P less than 0.001) and positively with plasma epinephrine (P less than 0.01) and heart rate (P less than 0.01). Serum phosphate was significantly lowered during infusion of epinephrine, increasing arterial plasma epinephrine within the lower pathophysiological range corresponding to arousal reactions. Serum concentrations of immunoreactive parathyroid hormone were unchanged. Thus, hypophosphatemia in patients with mild essential hypertension appears to be inversely related to sympathetic adrenal tone and may be caused by increased plasma epinephrine within pathophysiologic arterial concentrations.

Increased erythrocyte magnesium in never treated essential hypertension.

In the present study we aimed at evaluating the intracellular concentrations of magnesium, potassium and sodium in 50-year-old, otherwise healthy white men with never treated, essential hypertension (n = 12) and in normotensive control subjects (n = 12) matched for age, sex, race, height, weight and smoking habits. Intraerythrocyte magnesium was significantly increased in the hypertensive group (P less than .001) and correlated positively and significantly to blood pressure in the total group (P less than .01). The intracellular potassium to sodium ratio tended to be lower in the hypertensive group (P less than .05). Thus, the present study supports increased intracellular magnesium probably unrelated to intracellular potassium-sodium imbalance in never treated, essential hypertension.

Effect of dietary counselling on blood pressure and arterial plasma catecholamines in primary hypertension.

There is still a need of support for nonpharmacologic treatment of uncomplicated, mild-to-moderate essential hypertension. We investigated whether a low sodium-based diet implemented by a nutritionist could lower blood pressure and affect sympathetic activity. Middle-aged, otherwise healthy men with never-treated essential hypertension (n = 95) were randomized to an intervention group, a blood pressure control group, and a time control group. The intervention group was advised to use less sodium chloride in their diet, and if necessary, less saturated fat and decrease body weight. They attended regular clinic visits as did the blood pressure control group. After 1 year, the intervention group had achieved on average 72 mmol/24 h lower urinary sodium excretion (P < .001) and a decrease in body weight of 2.7 +/- 0.5 kg (P < .001). Both supine and standing mean blood pressure were on average 8 to 10 mm Hg lower after intervention compared with the two control groups (P < .001). Arterial plasma epinephrine, measured in all 40-year-old subjects (n = 30), decreased in parallel in all three groups (P < .05), indicating some habituation to the invasive procedure and clinic visits. However, the decrease in norepinephrine was significant (P < .001) only in the intervention group; it correlated with the weight loss (r = 0.76, P < .05) and was significantly higher (P < .05) than in both control groups. These results suggest that broad dietary advice (ie, low intake of sodium chloride, saturated fat and energy), implemented by a nutritionist, may have a significant blood pressure lowering effect and a favorable sympathicolytic effect in uncomplicated, mild-to-moderate essential hypertension.

Biphasic effect of epinephrine on blood glucose during hyperinsulinemia in borderline hypertensive young men.

We aimed to study the glycemic response to epinephrine during hyperinsulinemia and infused epinephrine (0.03 microg/kg/min) for 30 min after 90 min of hyperinsulinemic glucose clamp in 14 borderline hypertensive young men. Plasma epinephrine was increased from 0.34 +/- 0.08 to 2.33 +/- 0.33 nmol/L while insulin and glucose infusions were kept constant with consequent changes in blood glucose. Initially (90 to 95 min), there was a decrease in blood glucose (P = .016) that correlated negatively with glucose disposal rate corrected for insulin (r = -0.55, P = .040) and positively with fasting insulin (r = 0.55). Thereafter, there was an increase in blood glucose (95 to 120 min) (P < .001) that persisted during the recovery period (120 to 140 min). The glucose increase (90 to 140 min) correlated positively with fasting insulin (r = 0.55), systolic blood pressure (r = 0.57), delta epinephrine 90 to 120 min (r = 0.59), and baseline epinephrine (r = 0.57). Blood glucose remained unchanged (P = .207) in a saline control group (n = 6) with a significant group X treatment effect versus epinephrine (P = .003). Thus, epinephrine caused a biphasic response in blood glucose during hyperinsulinemia. The initial dip in glucose was more pronounced with higher insulin sensitivity, corresponding to previous observations during mental stress test. The following increment in blood glucose was positively related to insulin, systolic blood pressure, and epinephrine levels. These data suggest that insulin may modify the glycemic response to epinephrine in a potentially favorable direction and indicate some lag time before epinephrine gains effect. Subjects who are insulin sensitive and have low blood pressure and resting epinephrine levels seem to be less prone to hyperglycemia induced by epinephrine.

Effects of hyperinsulinemia on sympathetic responses to mental stress.

In a recent study, we could not find evidence to support the hypothesis that insulin activates the sympathetic nervous system (SNS) during a hyperinsulinemic glucose clamp procedure. Mental stress tests (MST), however, may be used to detect differences in blood pressure and SNS activity that are not present during baseline or resting conditions. In this study, we aimed to investigate the effects of hyperinsulinemia during glucose clamp on blood pressure and sympathetic responses to mental stress. Borderline hypertensive but otherwise healthy 21-year-old men (n = 18) underwent 5 min of mental arithmetic stress testing (MST-1) before and at the end of 120 min of isoglycemic hyperinsulinemic glucose clamp (MST-2) with infusion rates of glucose and insulin kept constant. Insulin concentration increased from 119 +/- 10 pmol/L to 752 +/- 65 pmol/L. We observed highly significant increases in blood pressure and heart rate in response to MST, but neither insulin nor saline solution infusions affected these responses. During MST-1, norepinephrine increased by 461 +/-165 pmol/L (mean +/- SEM) and epinephrine by 218 +/- 76 pmol/L. During MST-2 the changes were 372 +/- 112 pmol/L and 187 +/- 60 pmol/L, respectively. The norepinephrine (P = .8) and epinephrine (P = .7) responses were unchanged by insulin. Thus, there were similar increases in blood pressure, heart rate, and plasma catecholamine concentrations in arterialized venous blood in response to MST despite the infusion of insulin. A possible time effect was excluded by including a saline solution control group (n = 7) that showed almost identical results. Our results suggest that acute hyperinsulinemia during isoglycemic glucose clamp does not interfere with cardiovascular or sympathetic responses to mental stress.

Effects of losartan on insulin sensitivity in severe hypertension: connections through sympathetic nervous system activity?

Angiotensin II (Ang II) is one of the most potent vasoconstrictors, and the first specific and orally available Ang II-receptor antagonist, losartan (MK-954, DuP-753), has now come into clinical use. The primary site of insulin resistance, as measured by the glucose clamp technique, is skeletal muscle. Losartan specifically blocks Ang II-induced vasoconstriction, namely causes vasodilation, and may thus increase glucose delivery to skeletal muscle. We used the euglycaemic hyper-insulinaemic glucose clamp technique to assess insulin sensitivity (glucose disposal rate, GDR) or insulin (I) sensitivity index (GDR/I). In 21-year-old men we found negative correlations between GDR/I and blood viscosity (r = -0.69), haematocrit (r = -0.65), fibrinogen (r = -0.50), cholesterol/HDL ratio (r = -0.45), triglycerides (r = -0.46), body mass index (r = -0.64), waist/hip ratio (r = -0.57), resting heart rate (r = -0.46) and diastolic blood pressure (DBP) (r = -0.43), and with DBP (r = -0.62) and plasma adrenaline (r = -0.36) during mental arithmetic stress. In the Losartan Severe Hypertension Study five patients with a record of DBP > or = 115 mm Hg were examined before and on losartan monotherapy for an average of 6 weeks. GDR increased 27% and plasma noradrenaline decreased 40% (P < 0.05 for both) during treatment with losartan. Calculated whole blood viscosity decreased on losartan (P = 0.04) and the changes in GDR correlated with the changes in viscosity (r = 0.89). These results suggest that losartan, possibly by a sympathicolytic effect, lowers blood viscosity, causes vasodilation, and improves insulin sensitivity in essential hypertension.

Increased erythrocyte magnesium in untreated essential hypertension.

In the present study we tested the hypothesis of magnesium deficiency and intracellular magnesium depletion in essential hypertension. Atomic absorption was used to determine the erythrocyte content of magnesium in 50-year-old otherwise healthy white men with never-treated, essential hypertension (n = 12, supine blood pressure 155 +/- 4/109 +/- 2 mmHg) and in a group of particularly well-matched normotensive control subjects. The erythrocyte magnesium content was higher in the hypertensive group (P less than 0.001). No significant difference between the groups was detected for serum concentration or the 24-h urinary excretion of the magnesium. In conclusion, magnesium deficiency is unlikely in white middle-aged hypertensive men.

Metabolic and adrenergic characteristics of young men with insulin resistance.

The primary site of insulin resistance, as measured by the euglycaemic glucose clamp technique, is skeletal muscle. We used the euglycaemic hyperinsulinaemic glucose clamp technique to assess insulin sensitivity (glucose disposal rate, GDR). We aimed at clarifying the demographic, metabolic, haemorrheological, haemodynamic, and by mental stress test the adrenergic characteristics of 21-year-old men grouped in tertiles according to their insulin (I) sensitivity index (GDR/I); insulin resistant group (GDR/I < 5.5 a.u., n = 17), intermediate group (5.5 < GDR/I < 9.5 a.u., n = 16) and insulin sensitive group (GDR/I > 9.5 a.u., n = 17). Insulin resistance was characterized by higher body mass index (p = 0.002, analysis of variance), triglycerides (p = 0.001), total cholesterol/high density lipoprotein cholesterol ratio (p = 0.002), haemoglobin (p = 0.013), haematocrit (p = 0.017) and resting heart rate (p = 0.041) but not resting blood pressure or catecholamines in arterialized blood. However, the mental stress caused by announcement of a forthcoming arithmetic stress test increased diastolic blood pressure and plasma epinephrine dependent on insulin resistance (p = 0.006 and p = 0.012, respectively) with a similar trend also for the maximal increases in heart rate and plasma norepinephrine during arithmetic. Thus, in healthy young men, insulin resistance is not associated with differences in baseline blood pressure but is characterized by higher body weight, disorders in blood lipids and haemorrheology and a hyperadrenergic response to mental stress that even involves blood pressure. We suggest that the sympathetic nervous system may be involved in the pathophysiology of the characteristic insulin resistance or metabolic cardiovascular syndrome in young men.

Haemodynamic and neurohumoral effects of cold pressor test in severe heart failure.

The effect of a cold pressor test (CPT) on haemodynamics in relation to general and regional sympathetic activity and arginin vasopressin (AVP), was studied in eleven patients with severe congestive heart failure (CHF). Compared to an age-matched control group (C), resting arterial plasma noradrenaline (NA) (419 +/- 77 vs. 182 +/- 15 pg ml-1), and adrenaline (A) (142 +/- 28 vs 54 +/- 10 pg ml-1) were higher (P less than 0.05) in CHF. AVP showed no significant difference (14 +/- 4 vs. 9 +/- 4 pg ml-1). During CPT systolic and diastolic blood pressure and systemic vascular resistance increased (P less than 0.01), as did NA (delta 114 +/- 39 pg ml-1, P less than 0.01), A (delta 33 +/- 10 pg ml-1, P less than 0.01) and heart rate (delta 10 beats min-1, P less than 0.01). The myocardial v-a difference of NA decreased (P less than 0.05), but was unchanged across the renal vascular bed during CPT. The a-v difference of NA in the hepatic vascular bed, and fractional extraction of A in the coronary sinus, renal and hepatic vascular beds remained unchanged during CPT. AVP did not change significantly and no change in cardiac index or left ventricular filling pressure was observed during CPT. These data suggest that despite an increased activation of the sympathetic nervous system at rest, a further increase in blood pressure and catecholamines took place during CPT. Thus, the effect of a CPT which activates the central sympathetic system seems not to be altered in patients with severe CHF.

Increased erythrocyte magnesium content in essential hypertension.

The present study aimed at testing the hypothesis of decreased erythrocyte magnesium content and magnesium deficiency in essential hypertension. Atomic absorption was used to measure the erythrocyte content of total magnesium in 50-year-old otherwise healthy white males with essential hypertension (n = 12, blood pressure (mean +/- SE) 155 +/- 4/109 +/- 2 mmHg) that had never been treated and in normotensive control subjects (n = 12, blood pressure 128 +/- 2/88 +/- 1 mmHg) matched for age, sex, race, height, weight and smoking habits. The erythrocyte magnesium content was significantly increased in the hypertensive group (2.266 +/- 0.063 vs 1.903 +/- 0.069 mmol/l erythrocytes, p less than 0.001). No significant difference between the groups was detected for serum concentration or the 24-h urinary excretion of magnesium. In conclusion, the present study indicates increased rather than decreased erythrocyte content of magnesium in 50-year-old white males with 'never-treated', essential hypertension. Magnesium deficiency is, therefore, unlikely in this subset of critically selected and matched hypertensive patients.

Insulin modifies the glucose response to mental stress independently of forearm blood flow.

In the present study we aimed to reproduce and extend our recent finding that insulin infusion modifies the glucose response to mental stress and to determine whether the altered glucose response, i.e. glucose uptake, may be explained by a rise in forearm blood flow (FBF). The subjects were borderline hypertensive; there was one former blood pressure measurement > or =140/90 mm Hg, but otherwise they were healthy 21-year-old men. In the first series (n = 18) the subjects were exposed to a 5-min mental arithmetic stress test prior to (MST-1) and at the end of (MST-2) 120 min of hyperinsulinemic glucose clamp. Blood glucose was unchanged (0.067+/-0.05 mmol/l, p = 0.24) during MST-1 and decreased (-0.37+/-0.09 mmol/l, p = 0.001) during MST-2. Blood glucose also decreased in a second series (n = 28) in which the subjects were exposed to MST after 120 min of glucose clamp (-0.33+/-0.09 mmol/l , p = 0.001), and FBF increased from 4.4+/-0.4 to 7.7+/-1.1 ml/min/100 ml (p<0.0001). Glucose was unchanged (p = 0.48) in response to MST in a saline time control group (n = 8). However, FBF increased in response to MST from 3.7+/-0.5 to 7.0+/-1.2 ml/min/100 ml (p<0.01). The increase in FBF averaged 3.3 ml/min/100 ml in both groups. Serum insulin remained unchanged in response to MST in controls, but decreased in response to MST during insulin infusion in both series (p = 0.04 and p = 0.004, respectively). The fall in glucose in response to MST during insulin infusion correlated with glucose disposal rate (GDR) (r = -0.40, p = 0.034, n = 28) and inversely with fasting insulin (r = 0.52, p = 0.004, n = 28). Thus, insulin infusion alters the glucose response to mental stress, i.e. there is a decrease in blood glucose concentration concomitant with an increased uptake. This glucose uptake is unrelated to FBF, but related to higher skeletal muscle insulin sensitivity and inversely to the fasting insulin level. Our data therefore suggest that infused insulin modifies the stress response through a mechanism at the tissue level. It may be speculated whether insulin counteracts unfavourable effects of mental stress and sympathetic activation on glucose metabolism.

Increased forearm blood flow during glucose clamp is related neither to insulin sensitivity nor to hyperinsulinemia in borderline hypertensive young men.

It is controversial whether raised insulin within the physiological concentration range increases forearm blood flow (FBF). The aim of the present study was therefore to examine the effect of the isoglycemic hyperinsulinemic glucose clamp procedure on FBF and to relate the increase to the glucose disposal rate (GDR), i.e. insulin sensitivity. Borderline hypertensive young men were examined with the clamp technique or received saline infusion, and FBF was measured using plethysmography. It is of particular interest to study this group of subjects because their GDR correlates to a number of metabolic and hemodynamic variables, and these subjects hyperreact to stressful stimuli. There was no correlation between deltaFBF during clamp and GDR (r = -0.002, p = 0.99, n = 28). While serum insulin increased from 107 +/- 5 to 628 +/- 31 pmol/l in the hyperinsulinemic group and remained unchanged (135 +/- 11 vs 116 +/- 11 pmol/l) in the saline group, FBF increased from 3.5 +/- 0.3 to a maximum of 5.1 +/- 0.4 ml/min/100 ml (p < 0.001, n = 28) and from 2.8 +/- 0.5 to a maximum of 4.5 +/- 0.5 ml/min/100 ml (p = 0.01, n = 8), respectively. The increase in FBF (delta%) was similar in the two groups (p = 0.9). Thus, we could not demonstrate any relationship between insulin sensitivity and increments in FBF during hyperinsulinemic glucose clamp in borderline hypertensive young men. The moderate increases in FBF during insulin infusion with serum concentrations within the physiological range seem to be time-dependent and not caused by hyperinsulinemia.

Insulin resistance and sympathetic nervous system activity in hypertensive and normotensive premenopausal women.

The aim of the present study was to compare insulin sensitivity and catecholamine responses to insulin in lean, hypertensive (HT) and normotensive (NT) premenopausal women. HT (BP 149 5/99 +/- 2 mmHg, n = 14) and NT (BP 128 +/- 4/81 +/- 2 mmHg, n = 12) were matched for age (46 +/- 1 vs. 47 +/- 1 years) and body mass index. Insulin sensitivity was determined by fasting serum insulin, glucose disposal rate (GDR) and insulin sensitivity index (GDR/I) using euglycemic hyperinsulinemic glucose clamp technique. Sympathetic nervous system activity was assessed by plasma adrenaline and noradrenaline in arterialized venous blood at baseline and during euglycemic hyperinsulinemic glucose clamp. Insulin sensitivity index correlated negatively with total cholesterol in HT (r = -0.57, p < 0.05) and with body mass index (r = -0.42, p < 0.05, n = 26). The response in catecholamines to euglycemic hyperinsulinemia in HT differed from NT with an increase both in noradrenaline and adrenaline. Blood pressure and heart rate responses, however, did not differ between HT and NT. Fasting serum glucose did not differ between the two groups (4.7 +/- 0.1 mmol/l in HT vs. 4.9 +/- 0.1 mmol/l in NT), nor did fasting serum insulin (16 2 mU/l vs. 13 mU/l). Glucose disposal rate (8.8 +/- 0.5 vs. 8.7 +/- 0.7 mg kg-1 body weight min-1) and insulin sensitivity index were similar (7.3 +/- 0.8 vs. 7.6 +/- 0.8 arbitrary units). We conclude that in lean, premenopausal hypertensive women insulin sensitivity is not reduced compared with age- and weight-matched normotensive women, but the hypertensives respond to hyperinsulinemia with increased plasma catecholamines, i.e. sympathetic nervous systemic activity. Also, insulin sensitivity correlates negatively with serum cholesterol. Thus, an insulin-hyperadrenergic interaction may possibly be involved as a pathogenetic factor in lean hypertensive women.

[Refractory hypertension]. / Refraktaer hypertensjon.

Resistant hypertension is a common disorder in general practice, and poses a challenge to clinicians. It is generally defined as failure to reduce blood pressure adequately despite the use of at least three different antihypertensive agents with different modes of action. The importance of recognizing expansion of plasma volume as a mediator of resistance to therapy is emphasized. Some patients may have white-coat hypertension. An even larger group of patients may fail to comply with the prescribed medication. A good physician-patient relationship is vital, and education of the patient is crucial for obtaining better adherence to the medication.

[How to combine antihypertensive drugs?]. / Hvordan kombinere blodtrykkssenkende medikamenter?

Many hypertensive patients do not respond adequately to single-drug therapy and may therefore require two or more drugs to reach the treatment goal. The drugs used in combination therapy should have additive or synergistic effects on blood pressure. A potential benefit of combinations is to use lower doses of each drug, which may attenuate or abolish the occurrence of side effects. Different combinations are discussed, as well as the inhibition of compensatory mechanisms that may otherwise counteract the antihypertensive effect.