[Behavior of the lithium excretion fraction in hypertensive patients during variations of sodium intake]. / Comportamento della frazione di escrezione del litio nel paziente iperteso durante variazioni dell'introito sodico.

Fractional excretion of lithium (FeLi) is a marker of proximal tubular sodium reabsorption. During different sodium intakes (normal = 120 mEq/day, low = 40 mEq/day and high = 240 mEq/day) fractional lithium excretion was evaluated in essential hypertensive patients (n. 19) and control subjects (n. 5). Our data showed that FeLi was higher in hypertensives than in controls. Dividing hypertensives on the basis of blood-pressure sensitivity, salt resistant patients showed lower FeLi levels as compared to salt sensitive ones. Our findings indicate that proximal tubular sodium reabsorption is decreased in essential hypertension; this behavior is particularly evident in salt sensitive patients, suggesting that factors affecting proximal tubular function are activated in these patients in order to reduce the impairment of renal excretory capability.

Plasma insulin levels do not change during atrial natriuretic factor infusion in human essential hypertensives.

In order to evaluate the effects of atrial natriuretic factor (ANF) infusion on plasma insulin (IRI) in hypertension, 32 essential hypertensives (aged 40 to 62 years) were studied. After 1 week of pharmacologic washout under normal sodium intake (120 mEq of Na+/day), patients were randomly assigned to receive either ANF (0.04 micrograms/kg/min) or its vehicle (50 mL of isotonic saline) over a 60-min period in supine position. Plasma IRI and glucose were measured at -60, 0, 20, 40, 60, 120, 180, and 240 min (infusion time: from 0 to 60 min). Plasma levels of IRI and glucose did not change significantly during ANF infusion. On the contrary, after ANF discontinuation plasma IRI rose from levels of 13.5 +/- 6.4 microU/mL at 60 min to values of 20.1 +/- 11.3 microU/mL at 240 min (P less than .0001 v time 0). Plasma glucose showed a similar behavior, increasing from values of 100.4 +/- 5.0 mg/dL at 60 min to values of 120.0 +/- 5.1 mg/dL at 240 min (P less than .02 v time 0). Our findings suggest that ANF did not influence insulin release in hypertensives. The increase of plasma glucose and IRI observed after ANF discontinuation could be due to the relapse of sympathetic activity, suppressed during ANF infusion.

[Oral administration of extracted kallikrein to patients with essential arterial hypertension]. / Somministrazione orale di callicreina estrattiva in pazienti affetti da ipertensione arteriosa essenziale.

Reduced kallikrein excretion has been demonstrated in essential hypertension, suggesting an impairment of the renal kallikrein-kinin system. Therefore, we evaluated the efficacy and safety of oral kallikrein administration (glandular kallikrein derived form porcine pancreas) in 20 essential hypertensives (14 males and 6 females) aged between 34 and 62 years. Kallikrein was administered (150 U.I. three times daily) over a period of eight days, under normal sodium intake (120 mEq of Na+/day). After the kallikrein administration period, urinary kallikrein resulted increased (from 0.9 +/- 0.4 U/24h, normal value greater than 1.2 U/24h, to 1.6 +/- 1 U/24h; p less than 0.05). Blood pressure decreased (systolic: from 154.6 +/- 13.8 mmHg to 140.3 +/- 12.5 mmHg; p less than 0.01--diastolic: from 92.5 +/- 1.5 mmHg to 86 +/- 3.9 mmHg; p less than 0.025), while urinary excretion of sodium (from 96.7 +/- 16 mEq/24h to 119.1 +/- 32.2 mEq/24h; p less than 0.05) and potassium (from 36.7 +/- 11 mEq/24h to 43.5 +/- 12.8 mEq/24h; p less than 0.05) increased after kallikrein administration. We observed only a transient episode of gastric pain. In conclusion, kallikrein administration has a mild hypotensive effect in hypertensive patients, and is generally well tolerated. The antihypertensive action is probably due to the natriuretic effect of kallikrein.

Does mild autonomic neuropathy affect atrial natriuretic factor regulation in diabetic hypertensive patients?

The effect of postural changes on plasma atrial natriuretic factor (ANF) levels was investigated in 16 diabetic hypertensives (eight with and eight without mild autonomic neuropathy) and in 10 hypertensives. The presence of renal damage or secondary hypertension was excluded. All diabetic patients were in good metabolic control. In upright position, the mean levels of plasma ANF were of 23.1 +/- 7.6 pg/mL in neuropathic diabetic hypertensives, 24.2 +/- 8.3 pg/mL in diabetic hypertensives, and 21.6 +/- 6.7 in essential hypertensives. Percentage decrease observed after the assumption of supine position was 47 +/- 18, 50 +/- 10, and 46 +/- 13, respectively. No significant difference was found between hypertensives and diabetic hypertensives, even in the presence of mild autonomic neuropathy. Plasma ANF response to postural changes was similar in all groups.

[The efficacy and tolerance of orally administered kallikrein in patients with essential arterial hypertension]. / Efficacia e tollerabilità della somministrazione orale di callicreina in pazienti affetti da ipertensione arteriosa essenziale.

Since the reduced kallikrein excretion demonstrated in essential hypertension suggested the possibility of an impairment in the renal kallikrein-kinin system, we decided to evaluate the efficacy and safety of oral kallikrein administration (glandular kallikrein derived from porcine pancreas) in 30 essential hypertensive subjects (21 males, 9 females, age range 34-62 years). Twenty subjects took 150 IU kallikrein t.i.d. for eight days; during this period their sodium intake remained normal (120 mEq Na+/die). Ten subjects took placebo. After the trial period, urinary kallikrein in the active group increased from 0.9 +/- 0.4 U/24 h (normal value greater than 1.2 U/24 h) to 1.6 +/- 1 U/24 h (p less than 0.05); systolic and diastolic blood pressure decreased respectively from 154.6 +/- 13.8 mmHg to 140.3 +/- 12.5 mmHg (p less than 0.01) and from 92.5 +/- 1.5 mmHg to 86 +/- 3.9 mmHg (p less than 0.025); urinary sodium and potassium excretion increased respectively from 96.7 +/- 17 mEq/24 h to 119.1 +/- 32.3 mEq/24 h (p less than 0.05) and from 36.7 +/- 11 mEq/24 h to 43.5 +/- 12.8 mEq/24 h (p less than 0.05). One patient in the kallikrein group suffered a transient episode of gastric pain. No modifications of the parameters evaluated were observed in the placebo group. We conclude that kallikrein has a mild hypotensive effect in hypertensive subjects and is generally well-tolerated. Its antihypertensive effect is probably due to the sodiuretic action of the substance.

Noise stimulus in normal subjects: time-dependent blood pressure pattern assessment.

Environmental noise may have various effects on blood pressure. The aim of our study was to verify noise impact on blood pressure in normal young subjects, using the "white noise" stimulus. Thirty subjects (16 males and 14 females, median age 22 years) were studied. The presence of hypertension, hypertensive hereditibility and loss of acoustic acuity were criteria for exclusion. Noninvasive measurements of systolic and diastolic blood pressure at three-minute intervals were performed with an oscillometric system (Omega 1000, In Vivo Research), for each of four phases of the trial. After an initial rest phase (9 min) to avoid the patient's "alarm reaction," "white noise" with an intensity equal to 40, 100, and 40 adjusted decibels (dBa) was administered consecutively for 18 min (2nd phase), 9 min (3rd phase), and 18 min (4th phase), respectively. Preliminary analysis with standard statistical tools was not able to analyze the blood pressure patterns during the test. On the contrary, polygonal analysis, taking into account the "time-dependent" changes, showed that noise exposure (100 dBa) significantly increased systolic blood pressure in 22/30 subjects. However, systolic blood pressure rose only at the beginning of the 100 dBa exposure, indicating that stimulus changes rather than noise are key provoking factors in blood pressure increases.

[Correlations between circulation levels of natriuretic atrial peptide and urinary excretion of kallikrein in young normotensive and hypertensive subjects]. / Correlazioni tra livelli circolanti di peptide atriale natriuretico ed escrezione urinaria di callicreina nel giovane normoteso ed iperteso.

The relationships between atrial natriuretic peptide (ANP) and the renal sodium-modulating systems have not yet been completely examined. In particular, the relationships between ANP and the kinins system are almost unknown. We thus examined an extremely selected cohort of normotensive (n = 29, mean age 21 +/- 2 years) and hypertensive subjects (n = 51m mean age 21 +/- 2.9 years), both without hypertensive heredity. After 7 days under normal sodium intake (120 mEq of Na+/day), blood samples were taken in the morning on awaking, for radioimmunoassay of plasma levels of aldosterone, ANP and renin activity. Blood was again drawn after one active hour in orthostatism. We also evaluated urinary kallikrein excretion from urine collected over the previous 24 hours. Our results showed higher plasma levels of ANP in young hypertensives than in normotensives (statistical significance p less than 0.0025). Urinary excretion of kallikrein was markedly reduced (p less than 0.001) in the hypertensive group (0.46 +/- 0.3 U/24 h) compared to youths with normal blood pressure (0.79 +/- 0.24 U/24 h), in which a relationship between plasma ANP and urinary kallikrein was not evident; young hypertensives, on the other hand, showed an inverse correlation (r = -0.72; p less than 0.001). Finally, our investigation, aside from establishing the presence of high circulating ANP levels even at the initial phases of hypertension, points out a new possible means of feedback among sodium-modulating systems. The opposite relationship between ANP and urinary kallikrein excretion in young hypertensives could be attributed to reduced activity of the renal kinins system and a compensatory attempt on the part of ANP.

[Nitrendipine: evaluation of the duration of the antihypertensive effect at different doses using the conventional method and ambulatory monitoring of arterial pressure]. / Nitrendipina: valutazione della durata dell'effetto antipertensivo a dosaggi differenti con il metodo convenzionale e con il monitoraggio ambulatoriale della pressione arteriosa.

To evaluate the effect-duration of nitrendipine in 20 moderate essential hypertensives (aged from 42 to 66, mean +/- SD: 55 +/- 7) when treated with 20 mg once or twice a day, we utilized the blood pressure standard method of measurement and the ambulatory monitoring. Blood pressure determinations were made during the follow-up at 2- week intervals for 3 months, each measurement being made with a mercury sphygmomanometer, 24 +/- 3 hours after the last dose; laboratory parameters, 2 24-hour blood pressure monitoring (ICR 5200, Spacelabs) and standard ECG were performed at baseline and after 3 months. Following a 2-week run-in period with placebo bid (at 10.00 am and 10.00 pm) a 20 mg morning dose of nitrendipine was started continuing the administration of the placebo tablet at 10.00 pm. The dosage was changed to a twice active daily regimen, with an increase in the daily dose (20 mg twice a day) in those patients whose diastolic blood pressure remained greater than 90 mmHg after a 4-week control. After the twelfth week, another 2-week placebo run-in followed the active treatment. Supine blood pressure recorded after 3-month therapy, showed a significant (p less than 0.0001) reduction in both systolic and diastolic mean values (22/15 mmHg) at the end of active treatment in the 16 patients who ended the trial. In particular, the responders to 20 mg (5 patients) showed a blood pressure reduction of 18 mmHg in comparison with the run-in period; in the other group of responders to increasing dosage of 40 mg (11 patients), we observed a 8 mmHg diastolic blood pressure reduction at 28 days and a successive 7 mmHg at the end of the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effects of nicardipine in hypertensive patients with chronic kidney insufficiency]. / Effetti della nicardipina in pazienti ipertesi con insufficienza renale cronica.

There has been a increasing awareness that calcium antagonists may have beneficial effects on the kidney. Therefore we evaluated the renal and antihypertensive effects of nicardipine treatment in 12 hypertensive patients with chronic renal failure. The drug was given at a dose of 20 mg three times a day. Blood pressure was normalized in almost all cases while the indexes of renal function were improved. A transient deterioration of renal function, probably due to reduction of glomerular capillary pressure was observed in some cases. In conclusion, our data showed a beneficial effect on renal function during nicardipine therapy. This effect could be absent in the most advanced degree of renal damage.

Blood platelets and angiotensin II: angiotensin II release after platelet aggregation.

Recent studies have demonstrated the presence of angiotensin II (Ang II) in human platelets. The aim of the present study was to determine whether in vitro platelet aggregation induces Ang II release. We studied 20 healthy volunteers, and found that some aggregant stimuli can cause the platelet to release this peptide. Release of Ang II was greater with thrombin (40.7%) than with ADP (29%), while N-ethylmaleimide was almost ineffective. The release of Ang II following in vitro aggregant stimuli suggests that this may be one of the mechanisms through which platelets can locally modulate vascular tone and perhaps promote atherogenesis.

Effect of nicardipine on angiotensin II platelet content.

We evaluated the effect of nicardipine treatment on platelet angiotensin II content in 18 essential hypertensive patients. Nicardipine induced a decrease in platelet angiotensin II content in all patients (-14%), but particularly in 10 (P less than 0.05; -20.5%). No other differences were found between these patients and the others. Further investigations are required to determine whether platelet angiotensin II content reduction contributes to the prophylactic and therapeutic effects of calcium antagonists on atherosclerosis.

Relationship between vasopressin and the renin-angiotensin-aldosterone system in essential hypertension: effect of converting enzyme inhibitor on plasma vasopressin.

The effect of the chronic administration of captopril on plasma levels of vasopressin (PVP) were studied in 14 patients with moderate essential hypertension and 10 normal volunteers. All patients were studied after 10 days without drugs and under a constant diet (120 mmol sodium and 80 mmol potassium/day). Plasma levels of renin activity (PRA), aldosterone (PA) and PVP were assayed before and after captopril treatment (50-100 mg/day for 1 month). In addition to the well-known effect of captopril treatment on PRA and PA, a statistically significant reduction of PVP was observed. This finding suggests that the renin-angiotensin-aldosterone system influences vasopressin release, and its inhibitors may contribute to the absence of water retention during captopril treatment compared with the effect of other vasodilatory drugs.