Effects of canrenoate on red cell sodium transport and calf flow in essential hypertension.

The effects of potassium canrenoate (100 mg/day, orally for 1 month) on blood pressure, calf blood flow at rest and after ouabain (0.5 mg intravenous bolus), and red cell Na homeostasis were investigated in 15 patients (7 men, 8 women, aged 18 to 63) with essential hypertension and without peripheral vascular diseases. On placebo, acute intravenous ouabain administration significantly and transiently reduced calf flow and increased calf vascular resistance without affecting blood pressure. Canrenoate significantly decreased blood pressure (from 159 +/- 21/105 +/- 9 mm Hg to 141 +/- 14/94 +/- 10, P < .05) and the rise of calf resistance after intravenous ouabain bolus. The latter effect was variable, since it was inhibited almost completely in 8 patients and unaffected in the others. In the patients in whom exogenously administered ouabain was antagonized, canrenoate diminished blood pressure through vasodilation and heightened the red cell Na/K pump. None of these parameters changed significantly in the other patients. Thus these data suggest that the fall in vascular resistance induced by canrenoate is mediated, in part, by the antagonism of endogenous ouabain-like factors.

Na/H and Li/Na exchange in red blood cells of normotensive and hypertensive patients with insulin dependent diabetes mellitus (IDDM).

It has been shown that red blood cell Li/Na exchange, also called countertransport (Li/Na CTT) is increased in patients with insulin dependent diabetes mellitus (IDDM) with clinical or subclinical nephropathy and elevated blood pressure. Because recent experimental evidence confirms that red cell Li/Na CTT is a mode of functioning of the Na/H exchange (Na/H CTT), we have measured both transport modes in 23 IDDM (16 hypertensive and seven normotensive) and in eight normotensive controls with normal glucose tolerance. Na/H and Li/Na CTT were significantly increased in hypertensive compared to normotensive diabetics and controls. Na/H CTT was 78 +/- 28 mmol/L cell/h in hypertensive IDDM, 50 +/- 21 in normotensive IDDM, and 55 +/- 24 in the controls. Li/Na CTT was 0.37 +/- 0.13 mmol/L cell/h, 0.27 +/- 0.10, and 0.25 +/- 0.11, respectively. Na/H and Li/Na CTT were significantly correlated (r = .38, P less than .05). The proximal tubule sodium reabsorption, measured as the fractional Li+ reabsorption, was significantly correlated to red cell Na/H CTT (r = .38, n = 29, P less than .05), but not to the Li/Na CTT (r = .21, n = 29). In conclusion this work confirms that Na/H and Li/Na CTT are function modes of the same transporter and that an increased activity of Na/H CTT might play a role in the blood pressure increase in IDDM.

Red blood cell Na+/H+ and Li+/Na+ exchange in patients with essential hypertension.

The increased red blood cell Li+/Na+ exchange found in a subgroup of patients with essential hypertension (EH) may reflect an increased activity of the Na+/H+ exchange. The maximal velocity of the red cells' Na+/H+ (Na+ influx promoted by an outward H+ gradient) and Li+/Na+ (Li+ efflux promoted by external Na+) exchange were therefore measured in 41 EH and in 21 normotensive controls (NT). Both transporters were significantly higher in EH than in NT (74 +/- 39 mmol/L cell x h v 43 +/- 27 for the former, P less than .03, and 0.35 +/- 0.16 v 0.26 +/- 0.10 for the latter, P less than .05). Even though more than 100 times faster, Na+/H+ exchange was weakly but significantly correlated to Li+/Na+ exchange (r = 0.29, P less than .05). Proximal tubule Na+ reabsorption (fractional renal Li+ reabsorption) was significantly greater in EH than in NT (0.78 +/- 0.07, n = 32, v 0.73 +/- 0.06, n = 10, P less than .05) but it was not correlated to either the red cells' Na+/H+ or Li+/Na+ exchanges. Therefore, hyperactivity of Na+/H+ exchange in EH may play a role in blood pressure elevation through mechanisms other than stimulation of renal Na+ reabsorption.

Renal hemodynamic changes induced by hypertension and its treatment.

Essential hypertension is associated with increased intrarenal resistance that may go undetected unless the fractional distribution of cardiac output to the kidney is measured. Several hypotensive drugs induce a transient reduction of renal blood flow and glomerular filtration rate due to the reduction in renal perfusion. This may represent an untoward effect especially in subjects already presenting a clinically relevant reduction of renal function. Loop diuretics, cardioselective and intrinsic sympathomimetic activity (ISA) beta-blockers, calcium entry-blockers, and angiotensin-converting enzyme (ACE) inhibitors either do not significantly reduce or even increase renal perfusion. This is one more reason for considering these agents as first choice drugs for the treatment of hypertension.

Red blood cell membrane cation transport in normotensive psoriatics.

Psoriasis might be a widespread membrane disorder. To verify whether under the influence of psoriasis the red cell membrane cation metabolism is altered, we compared 46 psoriatics with 23 normotensive controls. A significant increase was observed in intracellular K+ content, in the maximal velocity of the Na(+)-K+ ATPase, of the Na(+)-K(+)-Cl- outward co-transport, of the Na+/H+ exchange, as well as in the outward passive permeability for Na+. No difference was seen between the two groups in Na+ content, Li+/Na+ exchange or in the passive permeability to K+. In 8 psoriatics treated with etretinate (10-75 mg/day for 1-36 months), Na(+)-K+ ATPase, Na(+)-K(+)-Cl- co-transport and the passive permeability for Na+ were not significantly different from controls. These results suggest that the primary abnormality might be an increased Na+ influx, in part through the Na+/H+ exchange, which is compensated by increased activity of outward transports, and confirm that the red cells are a useful model for the study of membrane transport in this disease. Our results indicate also that these membrane transport abnormalities can be corrected by etretinate treatment.

The duration of atrial fibrillation influences the long-term efficacy of low-energy internal cardioversion.

BACKGROUND: It is commonly held that long-lasting atrial fibrillation (AF), especially if associated with marked enlargement of the left atrium, is a negative predictive factor for both the recovery and the maintenance of sinus rhythm. The aim of the present study was to identify the clinical features of patients who have a greater likelihood of success both in the acute phase and, especially, in the medium-long term. METHODS: Since June 1997, we have performed low-energy internal cardioversion to 93 patients (66 males, 27 females, mean age 62 +/- 9 years, range 26-80 years) with a mean duration of AF of 922 +/- 1032 days. Seventy-four patients had heart disease and 19 isolated AF. External cardioversion had been previously performed in 79 patients to no avail. All patients underwent antiarrhythmic therapy and were followed for a period of 13 +/- 7 months. RESULTS: Low-energy internal cardioversion proved efficacious, restoring sinus rhythm, in 92% of patients (86/93) and inefficacious in 8% (7/93). In 24% (21/86) the procedure, although efficacious, was followed by early recurrence of AF which proved to be intractable in 52% (11/21). At the end of the session, 81% (75/93) of the patients maintained sinus rhythm. At the end of follow-up, 40% (38/93) maintained sinus rhythm. Of all the parameters considered in the two groups, the duration of AF was the only one which differed significantly between the group in sinus rhythm and that in AF, with regard to both the efficacy of the procedure in the acute phase (755 +/- 868 vs 1618 +/- 1359 days, p < 0.001) and the long-term outcome (655 +/- 5.8 vs 1107 +/- 1098 days, p < 0.05). CONCLUSIONS: AF lasting more than 2 years constitutes a negative predictive factor for both the recovery and the long-term maintenance of sinus rhythm.

Percutaneous transluminal renal angioplasty: influence of complications on long-term blood pressure results.

Natural history and outcome of percutaneous transluminal renal angioplasty (PTRA) in renovascular hypertension (RVH) were assessed retrospectively in 52 patients in whom 62 PTRAs were successfully performed. Complications were observed in 16 patients: prolonged and extensive arterial spasms in eight, severe intimal dissection of the main renal artery in five, arterial thrombosis at the site of PTRA in two and acute deterioration of renal function in one. All the complications cleared up with medical treatment except for one major dissection occluding the distal branches, which required surgery. According to the Co-operative Study, after 1-5 years of follow-up, 21 patients (40.4%) were cured, 27 (51.9%) improved and four (7.7%) did not improve. The long-term results on blood pressure in both uncomplicated and complicated cases were better in fibrodysplasia (61.5% cured, 34.6% improved and 3.8% not improved) than in atherosclerosis (17.4% cured, 69.6% improved and 13% not improved). In the last 21 PTRAs performed, in which verapamil (200-1500 micrograms) was given as a bolus injection into the stenotic artery before dilatation, the complication rate was significantly lower. It is concluded that PTRA is an effective treatment for RVH; complications occurred in 25.8% of PTRAs and resulted in poor control of blood pressure in atherosclerosis but not in fibrodysplasia; premedication with verapamil into the stenotic renal artery reduced the complication rate.

Plethysmographic effects of doxazosin in essential hypertensive patients.

In the treatment of hypertensive patients with peripheral vascular disease, alpha 1-adrenoceptor blockers may be considered first-choice drugs since they reduce the total peripheral resistance and do not decrease the plasma volume. As a preliminary step, we investigated the plethysmographic effects of doxazosin (1-8 mg for 6 weeks) on calf flow in 32 uncomplicated hypertensive patients. Despite the fall in sitting and standing blood pressure (from 163 +/- 18/101 +/- 6 to 147 +/- 19/94 +/- 8 mmHg and from 162 +/- 18/107 +/- 9 to 145 +/- 18/95 +/- 8 mmHg, respectively; both P less than 0.001) the calf flow was not decreased at rest and after ischaemia. Resting resistance was not significantly reduced (from 49.5 +/- 35 to 38.9 +/- 33 mmHg/100 ml per min) but its fall was significantly correlated with the fall in mean blood pressure (rs = 0.35, P less than 0.05). These findings confirm that doxazosin may be useful in the treatment of hypertension complicated by peripheral artery disease.

[Doppler tissue imaging in the study of the diastolic function in amyloidosis cardiopathy]. / Il Doppler tissue imaging nello studio della funzione diastolica nella cardiopatia amiloidosica.

Doppler tissue imaging (DTI) is an adaptation of the color-doppler, which allows the measurement of low-speed myocardial wall movement. We describe the case of a 51-year-old woman suffering from cardiac amyloidosis with serious endangerment of the diastolic function and mitral flow velocity pattern that was indistinguishable from the normal. The protodiastolic speed of the myocardial walls was measured with pulsed DTI, which was used as a diastolic function index. In this patient, the speed was 5 cm/sec, which was markedly lower than the values found in normal subjects and published recently. Moreover, the DTI M-mode images are examined here in order to point out different characteristics compared to the ones that can be obtained in normal subjects. This therefore exemplifies the possible use of this new technique in studying diastolic function.

Red blood cell sodium heteroexchange in familial primary hypertrophic cardiomyopathy.

The hallmark of primary hypertrophic cardiomyopathy is an inappropriate myocardial hypertrophy, linked to myofibril disarray of the left ventricle. Its variable clinical expression may be due to genetic heterogeneity and variable penetrance. Since we have recently shown that abnormalities of cation transport in the erythrocytes are associated with cardiac hypertrophy in essential hypertensives and insulin-dependent diabetics, we have investigated the relationship between cardiac anatomy and function and red cell Li+/Na+ and Na+/H+ exchange in 33 relatives of a patient who died of cardiac failure and was found to have a primary hypertrophic cardiomyopathy at autopsy. According to echocardiographic examination, 11 members of the family also had a hypertrophic cardiomyopathy, with a family distribution compatible with autosomal dominant genetic transmission and variable penetrance. Red cell Li+/Na+ and Na+/H+ exchange were not significantly different in the affected members as compared to the unaffected, but in the former, after correction for potentially confounding variables, interventricular septum thickness was positively correlated to Na+/H+ exchange and diastolic function (Area E/Area A and Vmax E/Vmax A) negatively correlated to Li+/Na+ exchange. Since a generalized overactivity of the cell membrane Na+/H+ exchange, reflected by increased Na+/H+ and Li+/Na+ exchanges in the red cells, could favour cellular growth and diastolic dysfunction, our data suggest that abnormalities of cell membrane cation transport could play a role in the phenotypic expression of hypertrophic cardiomyopathy.

Time course of changes in blood pressure, aldosterone and body fluids during enalapril treatment: a double-blind randomized study vs hydrochlorothiazide plus propranolol in essential hypertension.

Aldosterone suppression is said to play a major role in the long term hypotensive efficacy of angiotensin converting enzyme inhibitors. However, in previous reports from other laboratories, plasma volume has been found mostly increased and sodium balance sometimes positive. The effects of the angiotensin converting enzyme inhibitor enalapril (10-40 mg/day, p.o., for 6 weeks) on blood pressure, body fluid volumes, renal function and plasma aldosterone were compared to those of hydrochlorothiazide (50 mg/day, p.o.) alone for 2 weeks and in association with propranolol (80-160 mg/day, p.o.) for 4 more weeks during a randomized double-blind parallel study in 14 essential hypertensives. Hydrochlorothiazide alone and in combination with propranolol induced slight and not significant change in either blood pressure and body fluids. The maximum hypotensive response to enalapril was achieved only after 2 weeks of continuous treatment possibly because after 1 week the hypotensive efficacy was lessened by a significant (P less than 0.05) fluid retention secondary to a transient and not significant fall in renal perfusion. At this time aldosterone was not significantly changed compared to pretreatment values. After 6 weeks on enalapril, blood pressure was significantly reduced, plasma aldosterone further but not significantly decreased and extracellular fluid volume was normal. These findings indicate that aldosterone suppression contributes to the blood pressure lowering effect of enalapril by offsetting the salt and water retention observed on starting treatment and due to direct vasodilation.

[Volume of the extracellular liquid and renal function during short-term administration of angiotensin converting enzyme inhibitors in essential hypertension]. / Volume dei liquidi extracellulari e funzione renale in corso di somministrazione a breve termine di ACE-inibitori nell'iperteso essenziale.

Short term angiotensin converting enzyme inhibition may induce a transient salt and water retention in patients with hypertension or heart failure. To verify the glomerular and tubular effects of short term converting enzyme inhibition, thirteen patients with mild to moderate essential hypertension (WHO I-II) were treated orally either with perindopril (4 mg o.d.) or captopril (25 mg b.i.d.) for one week. Both drugs reduced supine mean blood pressure significantly (p less than 0.01) (perindopril from 126 +/- 11 to 108 +/- 7 mmHg, mean +/- SD, and captopril from 132 +/- 12 to 121 +/- 16). Plasma volume (radio-iodinated albumin space) was unchanged while mean extracellular fluid volume (inulin space) increased although not significantly (from 5.05 +/- 1.32 l/sqm to 5.71 +/- 2.21 with perindopril and from 4.96 +/- 2.6 to 5.6 +/- 1.7 with captopril). Sodium clearance decreased (from 1.4 +/- 0.6 to 1.1 +/- 0.5 ml/min 1.73 sqm with perindopril, p less than 0.05, and from 0.97 +/- 0.44 to 0.88 +/- 0.51 with captopril, n.s.). In 9 patients (6 on captopril and 3 on perindopril) extra-cellular fluid volume increased simultaneously with reduction in glomerular filtration rate and in proximal tubule sodium re-absorption as well as an increase in distal tubule sodium reabsorption. In these patients the changes in proximal and distal tubule sodium reabsorption were significantly (p = 0.05) different from those of the patients with no extra-cellular fluid expansion.(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril-stimulated renin in the diagnosis of restenosis after percutaneous transluminal renal angioplasty.

Recurrence of hypertension is reported in a considerable percentage of renovascular hypertensive patients treated by percutaneous transluminal angioplasty (PTRA); among the possible mechanisms for these failures, restenosis of the renal artery is the only correctable one. Since captopril stimulates renin secretion to a greater extent in renovascular than in essential hypertensive patients, we determined if it could be used to unmask significant restenosis in the patients with hypertension recurring after PTRA. Follow-up study was performed in 28 patients treated with PTRA. We found that captopril caused a greater increase in peripheral plasma renin activity in 8 of 8 cases who had recurrence of hypertension and restenosis than in 13 of 15 of the patients who did not. We suggest that the determination of captopril-stimulated renin may provide a useful, simple and economical tool for the detection of restenosis after PTRA.

Erythrocyte Li+/Na+ and Na+/H+ exchange, cardiac anatomy and function in insulin-dependent diabetics.

It has been proposed that an increased activity of cell membrane Na+/H+ exchange, mirrored by increased erythrocyte Li+/Na+ exchange, may facilitate cell hypertrophy and hyperplasia. Patients with insulin-dependent diabetes mellitus may develop a specific cardiomyopathy with systolic and diastolic abnormalities and increased thickness of the left ventricle. Therefore, we have investigated the relationships between erythrocyte Li+/Na+ and Na+/H+ exchange and echocardiographic parameters in 31 male insulin-dependent diabetics (aged 17-68), in good metabolic control. Three had untreated mild hypertension. In all patients the urinary albumin excretion rate was less than 200 micrograms min-1. Ten patients had a Li+/Na+ countertransport higher than 0.37 mmol l-1 cell h-1, the upper normal limit for our laboratory (0.49 +/- 0.10, mean +/- SD). In comparison with the patients with normal countertransport, they had increased interventricular septum thickness and relative wall thickness (h/r). End diastolic volume and cardiac index were reduced while blood pressure and urinary albumin excretion rate were similar. In the whole study group, interventricular septum thickness was significantly correlated to Li+/Na+ exchange (r = 0.61, P less than 0.001) and Na+/H+ exchange (r = 0.35, P less than 0.05), independently of the effect of age and blood pressure. Posterior wall thickness was correlated to Li+/Na+ exchange (r = 0.38, P less than 0.05) and h/r to Li+/Na+ exchange (r = 0.41, P less than 0.05) and to Na+/H+ exchange (r = 0.44, P less than 0.05). Li+/Na+ exchange was negatively correlated to cardiac index (r = -0.37, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

[Dynamic evaluation of the renin-angiotensin system with captopril in screening for renovascular hypertension]. / La valutazione dinamica del sistema renina-angiotensina con il captopril nello screening dell'ipertensione renovascolare.

In 69 hypertensive with suspected renovascular hypertension the response of plasma renin and angiotensin I to a single oral dose of Captopril (Captopril test) was determined. In 15 of the 16 patients found to have renal artery stenosis at angiography and cured by either revascularization or nephrectomy, Captopril stimulated both plasma renin activity and plasma angiotensin I to a far greater extent than in the majority of the 53 classified as essential hypertensives. False positives were limited to 8. Sensitivity and specificity were 94% and 85%, respectively. In the same series sequential renal angiophotoscan showed 100% sensitivity but a lower specificity (75%). In comparison, both the sensitivity and the specificity of rapid-sequence intravenous pielography, isotopic renogram and recumbent plasma renin activity were far less satisfactory. It is concluded that this simple, safe and economical test should be preferred to the other diagnostic procedures in the screening of renovascular hypertension. Its use in combination with renal angiophotoscan improves diagnostic reliability.

Red blood cell sodium and potassium fluxes in psoriatic patients.

Psoriasis might be a widespread membrane disorder. Therefore, the red blood cell sodium, potassium and lithium outward fluxes (through Na-K-ATPase, Na-K-Cl co-transport, Li-Na countertransport and passive permeability), as well as the Na and K content, were studied in 31 psoriatic patients and 23 normal controls. A significant increase in intracellular potassium content, in the maximal velocity of the Na-K ATPase and of Na-K-Cl co-transport as well as in the outward passive permeability for Na were found in the psoriatic patients compared with controls. On the contrary, no differences were observed in sodium content, Li-Na countertransport and passive potassium permeability between the two groups. These results are compatible with a selective increase in inward, as well as outward, membrane permeability to sodium, which is compensated for by increased activity of the Na-K pump, and of the outward Na-K-Cl cotransport with a secondarily increased erythrocyte potassium content. They indicate that the red blood cell might be a useful model for the study of membrane transport in psoriatics.

[Doxazosin for the treatment of arterial hypertension]. / La doxazosina nel trattamento dell'ipertensione arteriosa.

Hypertension is often associated to other risk factors, such as abnormal lipid and carbohydrate metabolism, which should be considered for the choice of antihypertensive drug treatment. Doxazosin is a postsynaptic alpha-1 adrenoceptor blocker suitable for once a day treatment regime. It seems to induce fewer side effects than older drugs of the same class and it may improve lipid and carbohydrate profile, thereby reducing the risk of coronary artery disease. To verify its effects on blood pressure, serum lipids and glucose tolerance, doxazosin (1-8 mg od) was given for 8 weeks to 32 patients suffering from essential hypertension, of whom 16 had fasting serum cholesterol higher than 6 mmol/l and/or fasting serum triglycerides higher than 1.9 mmol/l. Sitting and standing blood pressure were significantly reduced (from 163 +/- 18/101 +/- 6 mmHg to 147 +/- 19/94 +/- 8, p less than 0.001 and from 162 +/- 18/107 +/- 9 to 145 +/- 18/95 +/- 8, p less than 0.001, respectively) at a mean daily dose of 5 mg. Normotension or a good hypotensive response was achieved in 60% of the patients. The daily dose which turned out to be effective in 50% of the patients was 7 mg. The drug treatment was well tolerated and orthostatic hypotension was never observed either on starting treatment or on increasing dosage. Blood lipids and glucose tolerance were not significantly affected. Doxazosin is therefore an effective antihypertensive agent suitable for use in patients with essential hypertension alone or combined with hyperlipidemia.

[Erythrocyte Li/Na countertransport and correlated variables in a randomized sample of population]. / Il controtrasporto Li/Na eritrocitario e le variabili ad esso correlate in un campione randomizzato di popolazione.

A genetically determined alteration of the cell membrane sodium metabolism may play a role in the pathogenesis of essential hypertension. The most consistent finding in patients with essential hypertension is an increased red blood cell Li/Na exchange (countertransport). It is genetically determined but it is also associated to potentially confounding variables (body weight, race, age and so on). The present study investigates the relationship between red cell Li/Na countertransport and various potentially confounding variables in a random sample of the population. It shows that this membrane cation transport system is increased in males compared to females and significantly correlated to body mass index in males and to blood pressure, alcohol consumption and, negatively, to urinary calcium excretion in females. Since body weight and alcohol consumption are correlated to blood pressure in several epidemiological studies, it can be hypothesized that they influence blood pressure control through an alteration of the cell membrane sodium transport.