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Acute reductions in functioning renal mass result in increases in both sodium (U Na V) and potassium (U K V) excretion by the contralateral kidney (CK). We studied the role of endogenous opioids in this response. In control experiments acute unilateral nephrectomy (AUN) increased U Na V from 1,788 +/- 1,125 (SD) to 3,939 +/- 1,819 and U K V from 1,385 +/- 561 to 2,254 +/- 832 neq/min by the CK (P less than 0.005 for both); similar results occurred in rats undergoing acute unilateral ureteral occlusion (UUO). These increases occurred without overall change in GFR or mean arterial pressure. In rats receiving a continuous infusion of the opiate-receptor antagonist naloxone (0.3 mg . kg-1 . h-1) neither AUN nor UUO produced significant alterations in U Na V or U K V by the CK; naloxone infusion by itself did not alter GFR or basal rates of cation excretion. A separate group of rats was made tolerant to morphine by subcutaneous implantation of pellets containing 75 mg morphine base. In these rats, AUN also failed to produce any increase in U Na V or U K V by the CK. The results suggest that acute reductions in functioning renal mass produced by either AUN or UUO stimulate cation excretion by the remaining kidney through reflex pathways that involve opiate receptors.

We determined the role of ornithine decarboxylase (ODC) in compensatory renal hypertrophy (CRH) by relating renal ODC activity and polyamine content to kidney size, expressed as a percent of body weight, 1 wk after unilateral nephrectomy (UN). In normal rats, renal ODC activity increased from 11.0 +/- 7.4 (SD) to 36.7 +/- 15.4 pmol 14CO2.min-1.g wet wt-1 3 h after UN (P less than 0.002); 1 wk later the remaining kidney weight had increased from 0.38 to 0.46% body weight (P less than 0.001). Renal concentration of putrescine, the product of ODC's decarboxylation of ornithine, was increased 3, 8, and 48 h after UN, but concentrations of polyamines synthesized later in the pathway, spermidine and spermine, were not appreciably affected. Pretreatment with difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, as a 1% drinking water solution inhibited both base-line renal ODC activity and putrescine concentration as well as increases stimulated by UN, although concentrations of spermidine and spermine were not decreased. In these rats, CRH still occurred, since kidney weight increased from 0.36 to 0.46% (P less than 0.001). A 2% DFMO solution caused depletion of all three polyamines, but CRH took place nevertheless. In hypophysectomized rats, both increased renal ODC activity and CRH occurred as well, indicating that these two consequences of UN do not require intact pituitary function. Although increased renal ODC activity and CRH after UN are correlated in normal and hypophysectomized rats, CRH takes place in rats treated with DFMO despite inhibition of ODC activity and depletion of polyamines.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of chronic changes in sodium intake on the acute effects of atrial natriuretic peptide (ANP) on arterial pressure and fluid translocation was assessed in acutely binephrectomized rats. After 3 weeks of either low sodium or high sodium diet, animals were administered ANP at doses of 0.1 and 1 μg/kg/min. A marked and irreversible hypotensive response to ANP was observed with the higher infusion rate in the low sodium group, whereas blood pressure did not change significantly in the other groups. The effect of ANP on plasma protein concentration was less marked than that on hematocrit in all groups and was not significantly affected by sodium intake. The effect of both doses of ANP on hematocrit was enhanced in the high sodium group, indicating that the fluid shift out of the intravascular compartment was magnified by high sodium intake.

We evaluated the role of the renal nerves in the increased cation excretion by the contralateral kidney after acute unilateral nephrectomy (AUN) or unilateral ureteral occlusion (UUO) in anesthetized rats. Both AUN and UUO caused large increases in sodium (UNaV) and potassium excretion (UKV) by the control kidney without change in glomerular filtration rate or mean arterial pressure. Prior denervation of either the ipsilateral (experimental) kidney or the control kidney completely prevented the increase in UNaV and UKV after UUO. Prior denervation of either kidney also prevented the increase in UNaV after AUN. However, a significant kaliuresis persisted after AUN despite unilateral denervation although reduced in magnitude when compared with the increase in UKV after AUN with both kidneys innervated. These results indicate that the renal nerves play a major role in the excretory response of the control kidney after acute reduction in functioning renal mass. This role of the renal nerves may be through the activation of a renorenal reflex. The reflex is activated by afferents from the ipsilateral kidney; the efferent limb is composed of the renal nerves to the control kidney. This reflex can entirely account for the compensatory increase in cation excretion after UUO. However, a separate mechanism, not dependent on the renal nerves, contributes to UKV after AUN.

The possibility that calcium antagonists may alter extracellular fluid partition, as already suggested for atrial natriuretic peptide (ANP), was explored in anephric anesthetized rats by measuring changes in hematocrit and plasma proteins during infusion of synthetic ANP-(103-126) and the dihydropyridine derivative nicardipine. In response to ANP (1 micrograms.kg-1.min-1) or nicardipine (0.1 microgram.kg-1.min-1), which had a similar effect on arterial pressure, hematocrit increased by 9 +/- 0.1 and 5.4 +/- 0.3%, respectively, whereas plasma protein concentration increased to a lesser extent (3.9 +/- 0.3 and 3.7 +/- 0.2%, respectively). The simultaneous infusion of ANP and nicardipine had no additive effect on hematocrit, whereas the effect on arterial pressure was markedly enhanced. In additional experiments, an attempt was made to estimate the vascular leak of albumin in various tissues, using a quantitative Evans blue technique. Both ANP and nicardipine increased dye extravasation in skeletal and cardiac muscle, whereas ANP but not nicardipine increased extravasation in intestine. No significant change was observed in brain, liver, and lungs. These results suggest that nicardipine and ANP reduce plasma volume by an extrarenal mechanism. This fluid shift, possibly resulting from hemodynamic changes at the capillary level, is associated with a marked transfer of plasma albumin out of the vascular compartment.

1. Systemic, humoral and renal responses to isotonic volume expansion (1800 ml in 3 h) were assessed in normal subjects and patients with normal renin essential hypertension before and during captopril administration. 2. Essential hypertensive subjects had a greater natriuretic and diuretic response to volume expansion than had normotensive subjects. 3. Captopril induced a fall in pre-saline mean arterial pressure more marked in hypertensive (20 ± 3 mmHg) than in normotensive subjects (9 ± 2 mmHg) and did not produce any change in sodium balance. 4. Captopril exaggerated the response of arterial pressure to volume expansion since mean arterial pressure increased more markedly after than before captopril in both normotensive (18.7 ± 3.8%) and hypertensive subjects (16.9 ± 3.7%). 5. Captopril blunted the exaggerated natriuretic response to volume expansion observed in patients with essential hypertension, whereas the renal response was unchanged in normotensive subjects.

Several effects of the antihypertensive treatment with angiotensin converting-enzyme inhibitors (ACEI)--whether beneficial or detrimental--are best explained at the renal level. In the presence of a renal artery stenosis, the activation of the intrarenal renin-angiotensin system is first directed at maintaining glomerular filtration and intracapillary hydrostatic pressure through post-glomerular vasoconstriction. Long-term elevation of blood pressure is associated with a shift of the renal function curve, possibly linked with an alteration of the intrarenal renin-angiotensin system. Inhibition of the converting enzyme does affect the mechanisms of sodium conservation. In a subset of essential hypertensive subjects, ACEI may correct a subtle primary abnormality in modulation by sodium of renal (and adrenal) response(s) to angiotensin. Finally, the possibility of renal protection in circumstances such as diabetes mellitus, provides an exciting area of investigations for antihypertensive treatment with ACEI.

Peripheral edema without fluid retention is a common side effect of treatment with calcium antagonists (CA). The possibility that CA may alter extracellular fluid partition between plasma and interstitium, as suggested for atrial natriuretic peptide (ANP) was explored in binephrectomized anesthetized rats by measuring changes in hematocrit and plasma protein concentration during infusion of synthetic 103-126 ANP (Wy 47.663) and the dihydropyridine derivate nicardipine. After a forty minutes infusion of ANP (1 microgram/kg/mn), hematocrit and plasma protein increased 9.1 +/- 0.3 and 3.9 +/- 0.3 p. 100 respectively; the calculated loss of plasma volume during ANP infusion was 14.5 +/- 1.1 p. 100 as compared to 3.9 +/- 0.6 p. 100 in rats receiving vehicle only. Infusion of nicardipine at 1 microgram/kg/mn increased hematocrit by 5.7 +/- 0.2 p. 100 (corresponding to a 9.1 +/- 0.9 p. 100 decrease in plasma volume), and plasma proteins by 3.7 +/- 0.2 p. 100. To document and localize an alteration in vascular leak of proteins induced by the drugs, albumin-bound Evans blue (EB) extravasation was measured spectrophotometrically in different tissues after extraction by methyl-formamide. Both ANP and nicardipine increased vascular penetration of EB-albumin, mainly in skeletal and cardiac muscle; no changes was observed in brain, liver, spleen as compared to rats receiving the vehicle; ANP but not nicardipine increase EB-albumin permeability in intestine. These results suggest that nicardipine as well as ANP reduce plasma volume by increasing vascular leak of fluids and macromolecules.

17 alpha-hydroxylase deficiency is a rare form of congenital abnormality in steroid synthesis, usually associated with moderate arterial hypertension and suppression of the renin-angiotensin system in a young adult. We report on a 45 years old woman with malignant hypertension (220/135 mmHg, severe retinopathy with papilledema, progressive renal insufficiency with serum creatinine over 300 mumol/l) of recent onset. Biological exploration revealed a metabolic alkalosis, a moderate hypokalemia (3 mmol/l), with elevated urinary excretion of potassium. Plasma aldosterone concentration (33 ng/dl) and plasma renin activity (17 ng/ml/h) were elevated. Acute captopril administration was followed by a marked (-29 p. 100) decrease in mean arterial pressure. In this 46 XX patient, a primary amenorrhea had never been explored; clinical examination disclosed the absence of female secondary sex characteristics. Plasma cortisol was low (203 mmol/l) as were plasma androgens (testosterone 0.55, androstene dione 0.19, delta HEA less than 0.1 nmol/l respectively) and oestrogens (oestradiol 59 nmol/l). Elevated levels of progesterone and pregnenolone sulfate (12.1 and 2027 nmol/l respectively) contrasted with decreased levels of 17 OH progesterone (0.35 nmol/l). Computed tomography revealed a subnormal right adrenal gland and a pseudo-tumoral aspect on the left side. Treatment with dexamethasone and combined antihypertensive drugs (captopril, nifedipine and atenolol) resulted in normalisation of blood pressure and secretion of renin and aldosterone but renal function did not fully recovered. Thus, the hypertension of 17 alpha-hydroxylase deficiency can follow a malignant course in association with a marked activation of the renin-angiotensin system.

The effect of acute administration of the angiotensin-converting enzyme inhibitor captopril on arterial pressure, glomerular filtration rate, and renal plasma flow was assessed in 16 patients with severe congestive heart failure. Following administration of captopril, mean arterial pressure (MAP) fell in all cases, whereas effective renal plasma flow increased from 27% to 88% in 10 patients, remained unchanged in 4, and decreased by 60% and 93% in 2 patients in whom MAP fell to 54 and 47 mmHg, respectively. Effective renal plasma flow and glomerular filtration rate values achieved after captopril were both positively correlated with postcaptopril MAP. The results of this study suggest that the renin-angiotensin system plays a major role in the regulation of MAP and the renal vasoconstriction associated with severe congestive heart failure. However, angiotensin blockade may induce a deterioration in renal function in patients in whom arterial pressure falls to markedly low values, thus suggesting an influence in angiotensin in renal autoregulation in these patients.

Acute extracellular volume expansion (VE) by isotonic saline is associated with variable change in mean arterial pressure (MAP) in normotensive subjects (NT). Following VE by 1,800 ml isotonic saline in 3 h, two patterns of MAP response were observed in NT: either an increase by more than 10% (SS: sodium or VE sensitive, n = 12) or no change (NSS: non-sodium or VE sensitive, n = 14). We assessed in all subjects the response to VE of glomerular filtration rate (GFR), urinary sodium (UNaV) and kallikrein (UKalV) excretion rate, plasma renin activity (PRA) and aldosterone concentration (PAC). Family history of blood pressure was not different between the groups. In response to VE, MAP increased (88 +/- 3 to 102 +/- 4 mmHg) in group SS and did not change in group NSS (83 +/- 3 to 85 +/- 3 mmHg). Whilst UNaV measured during the hour prior to VE was similar in both groups, the total amount of sodium excreted during VE was higher in group SS than in group NSS (52 +/- 9 vs 32 +/- 3 mmol/3 h, p less than 0.05). Control GFR as well as changes in GFR associated with VE were similar in both groups. A similar decrease in PRA and PAC was observed in both groups and pre-VE values were identical. UKalV was lower in SS than NSS subjects during the pre-VE control jour (0.42 +/- 0.09 vs 0.74 nKat/h; p less than 0.05) and during VE (1.14 +/- 0.16 vs 2.5 vs 0.47 nKat/3 h; p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

The acute effects of nifedipine (20 mg capsules) on the blood pressure and renin-angiotensine system were studied in 108 subjects, 25 normotensives, 51 borderline hypertensives and 33 permanent essential hypertensives. The fall in mean blood pressure (MBP) was rapid (less than 30 minutes) and significant in all groups; the amplitude the hypotensive response expressed as a percentage of the basal MBP was directly related to the basal MBP value (r = 0.54, p less than 0.001). The amplitude of the response correlated with the control plasma renin activity only the group with permanent hypertension (r = - 0.40, p less than 0.025). The fall in blood pressure and the reflex sympathetic stimulation induced by nifedipine were not associated with an increased plasma renin activity. The plasma aldosterone concentrations varied only in the group of permanent hypertensive patients after nifedipine ( - 4 +/- 1 ng/dl, p less than 0.01).

Many factors have been implicated in the pathogenesis of myocardial hypertrophy, and the role of sodium has recently been suggested. In the present study, we assessed the influence of dietary sodium on the degree of left ventricular hypertrophy (LVH) in 41 patients aged 38 +/- 10 (mean +/- SD) with mild essential hypertension (casual blood pressure 149 +/- 17/91 +/- 11 mmHg). Patients had never been given antihypertensive drugs before and ingested ad libitum sodium intake. Posterior wall thickness (PWT) and left ventricular mass (LVM) were measured by M-mode echocardiography and sodium intake was estimated from urinary sodium excretion rate (UNa, mmol/24h). Both PWT and LVM, and not telediastolic diameter or LV fractional shortening, were directly correlated with UNa (r = 0.47 and 0.46; p less than 0.02 and 0.002, respectively. A stepwise multiple regression analysis confirmed that UNa was a determinant of LVM independently of sex, age, body weight, blood pressure and duration of hypertension. No correlation was found between LVM and plasma renin activity, whilst a positive one existed between PWT and hematocrit (r = 0.42; p less than 0.007). These results suggest that dietary sodium may play a role in modulating left ventricular mass in untreated hypertensives, possibly in expanding volume or activating the adrenergic system.

Angiotensin converting enzyme (ACE) inhibitors are useful in the treatment of hypertension. However, acute renal deterioration may occur in some conditions where angiotensin plays a crucial role in the regulation of the glomerular filtration rate (GFR), such as volume depletion, severe stenosis of both renal arteries and stenosis of the renal artery of a single functioning kidney. Acute renal failure induced by ACE inhibition may develop without a reduction in systemic blood pressure it is enhanced by prior sodium depletion and is reversible when treatment is withdrawn. The relative superiority of ACE inhibitors in slowing the progression of chronic parenchymal renal disease remains to be demonstrated, although promising results have been reported in patients with diabetic nephropathy.

1. Systemic, humoral and renal responses to isotonic volume expansion (1800 ml in 3 h) were assessed in normal subjects before and during captopril administration. 2. Captopril, which otherwise induced a decrease in pre-saline mean arterial pressure (MAP), unmasked the volume-dependence of MAP, which increased linearly during volume expansion (+ 18.7 ± 3.8% at the end of volume expansion). 3. Captopril prevented the fall in plasma aldosterone produced by volume expansion but did not modify the natriuretic response to saline. 4. These results suggest that intrarenal rather than circulating angiotensin II may be one of the determinants of the natriuretic response to volume expansion in normal man.

An exaggerated natriuretic response to volume expansion (VE) is observed in many essential hypertensive patients. The plasma levels of atrial natriuretic peptide (ANP) were measured in 11 normal subjects (NT) and 12 patients with mild essential hypertension (EH) during VE (1 800 ml isotonic saline IV over 3 hours). NT and EH groups were similar with respect to age and basal levels of renin, aldosterone and ANP (34.5 +/- 5.5 in NT and 32.5 +/- 6.3 pg/ml in EH, mean +/- sem). In response to VE, ANP increased to the same extent in both groups (a change of + 19.3 +/- 5.2 in NT and 22.2 +/- 7.1 pg/ml in EH) despite the marked difference in observed natriuresis (36 +/- 3.5 in NT and 54.9 +/- 6.3 mmol/3 in EH, p less than 0.02). The change in ANP induced by VE was inversely correlated with the fall in hematocrit and the variation in fractional excretion of sodium in both groups. These results suggest that atrial natriuretic peptide may participate in the control of the renal response to isotonic volume expansion, but they do not support a predominant role of atrial natriuretic peptide in the exaggerated natriuretic responses to volume expansion of patients with essential hypertension.

Nifedipine, in a slow release preparation, was given at a mean daily dosage of 47 +/- 4 mg to 12 patients with severe hypertension in whom arterial pressure was not satisfactorily controlled (mean blood pressure, 172 +/- 6/111 +/- 4 mmHg) by the association of a converting enzyme inhibitor and a diuretic. Nifedipine administration induced a marked decrease in blood pressure (to 133 +/- 3/85 +/- 3 mmHg), serum potassium and plasma aldosterone. Following adequate control of hypertension and because of severe hypokalaemia in some patients, the diuretic was discontinued in 10 subjects. After 1.7 +/- 0.5 months of treatment by the converting enzyme inhibitor and nifedipine, no change in arterial pressure occurred whilst serum potassium returned to normal in most patients. These results demonstrate that nifedipine may be useful in patients with residual elevation of arterial pressure when treated by converting enzyme inhibitor and diuretic. However, in such patients serum potassium level should be carefully monitored. In addition, our observations suggest that calcium blockers may be an effective alternative to diuretics in patients receiving a converting enzyme inhibitor.

Systemic, humoral and renal responses to isotonic volume expansion (VE, 1800ml in 3 hours) were assessed in normal subjects before and during captopril administration (CEI). Captopril, which otherwise induced a decrease in pre-saline mean arterial pressure (MAP) unmasked the volume-dependence of MAP since during captopril administration MAP increased linearly during volume expansion (+18.7 +/- 3.8% at the end of VE). In addition, captopril prevented the fall in plasma aldosterone produced by VE but did not modify the natriuretic response to saline. These results demonstrate that circulating angiotensin II is not an important determinant of the natriuretic response to volume expansion in normal man. However, a role for intrarenal renin cannot be excluded.

Deterioration of renal function may be elicited by converting enzyme inhibition (CEI) in patients with bilateral (BI) or solitary kidney (SK) renal artery stenosis, but the determinants of this complication are not clearly delimited. The effect of acute administration of captopril on arterial pressure, glomerular filtration rate (GFR) and effective renal plasma flow was assessed in 10 BI and 10 SK hypertensive patients with a mean GFR of 64 +/- 5 ml/min. CEI induced a decrease in MAP of 8 +/- 2 p. 100 and a fall in GFR of 25 +/- 8 p. 100; GFR fell by more than 20 p. 100 in 5/10 BI and 8/10 SK. Filtration fraction (FF) decreased by 16 +/- 5 p. 100. CEI-induced change in GFR was not related to the change in MAP, but was inversely correlated with pre-C FF; GFR always fell when FF was higher than 0.28. Surgical correction of the stenosis suppressed the C-induced decrease in GFR in 5 SK patients in whom it initially fell. In conclusion, basal FF, a probable index of intrarenal angiotensin II activity, rather than a fall in systemic blood pressure, is the main predictor of acute deterioration of renal function after converting enzyme inhibition.

The effect of a six-week treatment by placebo, the calcium channel blocker nifedipine or the converting enzyme inhibitor captopril was assessed in normotensive patients with insulin-dependent diabetes and incipient nephropathy. In response to captopril and nifedipine, arterial pressure decreased slightly and to a similar extent. These drugs resulted in opposite effects on urinary albumin excretion (increase in urinary albumin excretion by 40% during nifedipine and decrease by 40% during captopril treatment). No change in urinary albumin excretion was observed in the placebo group. This observation of opposite changes in urinary albumin excretion in the presence of a similar fall in arterial pressure suggests that the effect of captopril and nifedipine on urinary albumin excretion results from some difference in their intrarenal action.

Both acute unilateral nephrectomy (AUN) and unilateral ureteral obstruction (UUO) result in an acute increase in cation excretion from the contralateral kidney. AUN results in reflex changes in systemic hemodynamics owing to an acute and transient increase in arterial pressure that activates carotid sinus baroreceptors and constitutes an afferent limb in the reflex; hemodynamic adjustments and increased cation excretion result. The reflex involves participation of the endogenous opioid system, with receptors located primarily in the central nervous system, and requires intact pituitary function because both hypophysectomy and pretreatment with large doses of dexamethasone prevent the postnephrectomy natriuresis. The natriuresis is closely correlated with an increase in the plasma concentration of the NH2-terminal fragment of the pituitary peptide precursor molecule proopiomelanocortin, which suggests that such a peptide could participate directly or indirectly in the postnephrectomy natriuresis. Surgical denervation of either the ipsilateral or the contralateral kidney markedly alters the response to AUN, which prevents the natriuresis and blunts the kaliuresis, and indicates a role for renal neural reflexes. Renorenal reflex pathways also mediate the response of the contralateral kidney to UUO, because denervation of either the ipsilateral (obstructed) or the contralateral kidney abolishes both the natriuresis and kaliuresis usually seen after UUO. This reflex also involves the endogenous opioid system, for it does not occur in rats receiving an i.v. infusion of the opiate receptor antagonist naloxone.

A case of pituitary adenoma in a 55 years old man was revealed by sudden pituitary apoplexy due to haemorragic necrosis of the tumor. Neurological signs were intracranial hypertension, epistaxis and evolutive bilateral ophtalmoplegia. Case history revealed a multiple endocrine neoplasia including a pancreatic insuloma and a parathyroïd adenoma. Biological data were hypercalcemia, hypophosphoremia and elevated serum levels of prolactine and parathormone. The characteristic features of pituitary haemorragic necrosis and multiple endocrine neoplasia are reviewed.

Deterioration of renal function is a major concern during treatment by converting enzyme inhibitors of hypertensive kidney recipients with transplant renal artery stenosis. However, there has been no assessment of the frequency of this complication and its specificity for converting enzyme inhibitors as compared to other antihypertensive drugs. The effect of acute administration of captopril on mean arterial pressure, glomerular filtration rate (GFR) (creatinine clearance) and effective renal plasma flow (clearance of 131I-hippuran) was assessed in eight hypertensive patients with transplant renal artery stenosis. Captopril induced a decrease in mean arterial pressure (128 +/- 6-121 +/- 7 mmHg) and a reduction in GFR (59 +/- 8-44 +/- 8 ml/min per 1.73 m2, P less than 0.05). The decrease in GFR was observed in seven out of eight patients and varied between 0% and 100% of the pre-captopril value. Effective renal plasma flow was maintained (157 +/- 47-141 +/- 24 ml/min per 1.73 m2) and filtration fraction decreased by 15 +/- 7%. The effect of captopril was compared to that of nifedipine (N = 20 mg) in four patients. Despite a larger decrease in mean arterial pressure (130 +/- 7-109 +/- 10 mmHg), no reduction in GFR was observed (68 +/- 13-71.4 +/- 8). Effective renal plasma flow was unchanged and filtration function slightly increased. Surgical or percutaneous transluminal angioplasty in five patients suppressed the captopril-induced decrease in GFR.(ABSTRACT TRUNCATED AT 250 WORDS)

Prolactin-secreting adenoma is probably the most common functional pituitary tumour in type I multiple endocrine neoplasia (MEN I). The authors report on a case of gastrinoma and parathyroid adenoma associated with prolactinoma. The latter tumour was revealed by sudden pituitary apoplexy. The characteristic features of endocrine tumours in MEN 1 are discussed, and the relevant literature is reviewed. Emphasis is placed on the fact that prolactinomas are well tolerated, remain clinically silent for a long time and may be diagnosed only when dramatic symptoms suddenly appear.

Calcium blockers of the dihydropyridine group may affect serum potassium level through an influence on the epinephrine mediated fall in serum K+. The effect of epinephrine infusion (12.5, 25 and 50 ng/kg/min) was assessed during placebo and after a 4-day treatment by nitrendipine in normal man. Nitrendipine treatment was associated with an enhancement in the fall of serum potassium induced by epinephrine. By contrast the response of arterial pressure, heart rate as well as the increase in blood glucose, plasma renin activity and the fall in plasma aldosterone and serum insulin levels induced by epinephrine were not affected by nitrendipine. Nitrendipine may potentiate the Na, K-ATPase stimulatory effect of epinephrine. Serum potassium should be carefully monitored in clinical situations associated with a consistent increase in circulating levels of epinephrine.

The acute hypotensive and renal effects of the calcium antagonist tiapamil, a verapamil derivative, were studied in nine normal and 13 essential hypertensive subjects undergoing water diuresis. Tiapamil decreased mean arterial pressure slightly in normotensive subjects and more markedly in hypertensive patients (-6 +/- 1 versus -10 +/- 2%). The effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were unaffected in both groups. A striking natriuresis was observed selectively in the hypertensive group (+344 +/- 84 versus +42 +/- 22 mmol/min) and was associated with an increase in the calculated fractional distal delivery of sodium and uric acid excretion rate. Plasma aldosterone concentration decreased moderately and to the same extent in both groups. In conclusion, tiapamil induced a marked natriuresis in essential hypertensive patients, despite a decrease in blood pressure, and in the absence of renal vasodilatation; this may suggest the existence in essential hypertension of a calcium-linked abnormality in the renal proximal tubular handling of sodium.