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The effect of acute hypercalcemia on blood pressure, blood volume, hemodynamic parameters, plasma norepinephrine, epinephrine, dopamine, renin, and aldosterone concentrations was investigated. After 1 hour of equilibration, 10 patients received an infusion of calcium gluconate in 5% dextrose (calcium 15 mg/kg of body wt in 3 hours). The calcium infusion increased the mean serum calcium from 8.7 to 13.0 mg/dl, the systolic blood pressure from 144 +/- 10 to 184 +/- (SEM) 12 mm Hg (P less than 0.001), the diastolic pressure from 78 +/- 4 to 93 +/- 5 mm Hg (P less than 0.01). The plasma volume was decreased by 9% (P less than 0.001), whereas the hematocrit was increased (P less than 0.05). Heart rate and cardiac output remained unchanged. Total peripheral resistance was increased from 1643 +/- 223 to 2256 +/- 387 dyne.sec/cm5 (P less than 0.05). The plasma epinephrine concentration rose from 4.5 +/- 0.7 to 6.9 +/- 1.2 ng/dl (P less than 0.01). The plasma norepinephrine concentration was unchanged after 2 hours and increased only slightly after 3 hours of calcium infusion. Plasma renin, aldosterone, and dopamine concentrations were not significantly changed. These findings demonstrate that acute hypercalcemic hypertension is mediated by an increase in peripheral vascular resistance. Hypercalcemic hypertension may be induced by a direct effect of calcium on blood vessels; calcium-mediated increase in adrenal epinephrine release may play a mild contributory role, and plasma volume contraction, an inhibitory role.

Interrelations among plasma renin activity (PRA), aldosterone and cortisole levels, 0lood volume, exchangeable sodium, urinary catecholamines, and blood pressure were studied in 35 normal subjects and 60 age-matched non-azotemic patients with diabetes mellitus (60% with hypertension, 15% with orthostatic hypotension). Basal PRA, plasma aldosterone, cortisol, blood volume, plasma potassium, and urinary electrolytes were comparable in diabetic and normal subjects. Diabetic patients, however, had a 10% increase in body sodium (P less than 0.01), and 8% of them showed normal postural PRA responses and subnormal aldosterone responses; 22% had subnormal PRA and normal aldosterone responses, and 17% had subnormal responses of PRA and aldosterone. Non-PRA-related aldosterone responses could not be explained by ACTH or electrolytes. Orthostatic decreases in blood pressure correlated (P less than 0.01) with both catecholamine excretion and basal PRA. This suggests that in diabetes mellitus, body sodium is increased. Basal PRA and plasma aldosterone are usually normal, but their postural responses are frequently impaired. Absent aldosterone responses, despite normal PRA responsiveness, may reflect an adrenal abnormality or an ineffective form of renin. Marked postural aldosterone stimulation, unrelated to PRA, ACTH, or electrolytes, points to a potent unknown factor in aldosterone control. Low levels of free peripheral catecholamines and PRA may be complementary factors contributing to postural hypotension.

1. Exchangeable sodium (NaE), plasma electrolytes and arterial pressure were measured in 121 normal subjects and 91 patients with untreated essential hypertension (diastolic greater than 100 mmHg), 21 of whom had low-renin hypertension. Plasma concentrations of renin, angiotensin II and aldosterone were measured in all hypertensive patients, total body sodium, total body potassium and exchangeable potassium (KE) in some patients. 2. Mean NaE was not different in normal and hypertensive subjects provided the two groups were matched for leanness index. In the subgroup of young hypertensive patients aged 35 years or less mean NaE was below normal. NaE was not related to arterial pressure in normal subjects but in hypertensive patients there were positive and significant correlations of arterial pressure with NaE and with total body sodium. 3. NaE and total body sodium increased with age in hypertensive but not in normal subjects. Partial regression analysis suggested that the correlation of NaE with arterial pressure was not explained by an influence of age. 4. Mean NaE was not increased and mean KE was not decreased in patients with low-renin hypertension. 5. Plasma potassium concentration, KE and total body potassium correlated inversely and significantly with blood pressure in hypertensive patients. These correlations were more marked in young than in old patients. 6. Multiple regression analysis showed that the combination of NaE and plasma potassium concentration 'explained' more of the variation of systolic blood pressure in hypertensive patients than it did in normal subjects. Plasma potassium concentration 'explained' more of the variation in young hypertensives and NaE 'explained' more in older patients. 7. Our findings suggest than changes of plasma and body potassium are important in the earlier stages of essential hypertension and that changes of body sodium become important later.

Hypertension accompanying diabetes mellitus may involve abnormalities in at least two major blood pressure-regulating systems: the body sodium-fluid volume state and cardiovascular reactivity. In metabolically stable nonazotemie diabetes, exchangeable sodium is increased by 10% on average, regardless of age, insulin dependence or nondependence, or the presence or absence of diabetic retinopathy or clinical nephropathy (proteinuria > 0.3 g/24 hr). Possible contributing mechanisms include renal sodium retention and an extravascular shift of fluid and sodium; intracellular accumulation is not excluded. Circulatory volume is normal or low and the total exchangeable sodium/blood volume ratio increased. In hypertensive diabetes, the latter abnormality is particularly pronounced; systolic pressure tended to correlate with exchangeable sodium (r = 0.47, p < 0.001) and diastolic pressure with the plasma sodium/potassium ratio (r = 0.25, p < 0.05). Plasma aldosterone, renin, epinephrine, and norepinephrine levels are generally normal or sometimes low in metabolically stable nonazotemie diabetic patients with normal or high blood pressure; the plasma clearance of norepinephrine also appears to be unaltered. The cardiovascular pressor responsiveness to norepinephrine is often exaggerated relative to concomitant plasma concentrations, regardless of age, type of antidiabetic treatment, or presence or absence of diabetic retinopathy, peripheral neuropathy, or high blood pressure. Pressor responsiveness to angiotensin II also may sometimes be increased relative to plasma renin levels. Sodium retention and diabetic vasculopathy of resistance vessels could be important complementary mechanisms of hyperreactivity. In diabetes with mild hypertension, diuretic treatment restored exchangeable sodium, norepinephrine pressor responsiveness, and blood pressure toward normal. Thus sodium retention and cardiovascular hyperreactivity tend to occur even at the normotensive, nonazotemie stage of diabetes and may concomitantly predispose for the frequent development of hypertension in the diabetic population. (Hypertension 7 [Suppl II]: II-33- II-42, 1985) KEY WORDS • body sodium-fluid volume state • sympathetic system • renin-angiotensin system • cardiovascular responsiveness • aldosterone • antihypertensive treatment

Interrelations between age and plasma renin, aldosterone and cortisol levels, urinary catecholamiens, plasma and blood volumes, exchangeable body sodium and blood pressure wwere studied in 28 young (19 to 29 years), 16 middle-aged (32 to 58 years) and 15 elderly (60 to 74 years) healthy subjects. Supine and upright plasma renin and supine aldosterone levels decreased while urinary noradrenaline excretion rate increased progressively with aging (r= greater than 0.34; p less than 0.05), with significant differences in mean values between young and elderly subjects (p less than 0.02). There was also an age-related decrease in upright plasma aldosterone concentration, although this was no statistically significant. Furthermore, mean plasma cortisol concentrations increased in response to upright posture in elderly ( + 50%; p less than 0.02), but not in young ( --10%) or middle-aged ( --8%) subjects. Blood pressure correlated with age ( r =0.35; p less than 0.05) or noradrenaline excretion rate ( r= 0.34) in the entire study population and with blood volume in the elderly ( r = 0.68), but not in the young or middle-aged study. Groups. There were no significant age-related differences in the body sodium/volume state, basal plasma cortisol levels or urinary adrenaline excretion rate, and plasma renin or aldosterone levels did not correlate with these parameters or with blood pressure. It is concluded that the influence of age on plasma renin or aldosterone levels, plasma cortisol responsiveness to upright posture, and urinary noradrenaline excretion should be taken into consideration, whenever these factors have to be interpreted in patients with arterial hypertension or other clinical disorders. Further more, these data are conssitent with the possiblity that in normal man increases in supine blood pressure with aging may be related at least partly to concomitant changes in free peripheral noradrenaline.

A study was carried out of arterial pressure and body content of electrolytes in 91 patients with essential hypertension and 121 normal controls. Exchangeable sodium was found to be positively correlated with arterial pressure in the patients, the correlation being closest in older patients; values of exchangeable sodium were subnormal in young patients; and plasma, exchangeable, and total body potassium correlated inversely with arterial pressure in the patients, the correlations being closest in young patients. Three hypotheses were proposed to explain the mechanisms relating electrolytes and arterial pressure in essential hypertension-namely, a cell-salt hypothesis, a dietary salt hypothesis, and a kidney-salt hypothesis.It was concluded that two mechanisms probably operate in essential hypertension. In the early stages of the disease blood pressure is raised by an abnormal process related more closely to potassium than to sodium. A renal lesion develops later, possibly as a consequence of the hypertension. This lesion is characterised by resetting of pressure natriuresis and is manifest by an abnormal relation between body sodium and arterial pressure and by susceptibility to increased dietary sodium intake.