Biomedical subjects

O L Pedersen

Publications and source records attributed to O L Pedersen.

At least 19 recordsLinked to original sources

PubMed2004

Incidence of atrial fibrillation and thromboembolism in a randomised trial of atrial versus dual chamber pacing in 177 patients with sick sinus syndrome.

OBJECTIVE: To analyse the occurrence of atrial fibrillation (AF) and thromboembolism in a randomised comparison of rate adaptive single chamber atrial pacing (AAIR) and dual chamber pacing (DDDR) in patients with sick sinus syndrome and normal atrioventricular (AV) conduction, in which left atrial dilatation and decreased left ventricular fractional shortening had been observed in the DDDR group. METHODS: 177 consecutive patients with sick sinus syndrome (mean (SD) age 74 (9) years, 104 women) were randomly assigned to treatment with one of three pacemakers: AAIR (n = 54), DDDR with a short rate adaptive AV delay (n = 60) (DDDR-s); or DDDR with a fixed long AV delay (n = 63) (DDDR-l). Analysis was intention to treat. RESULTS: Mean follow up was 2.9 (1.1) years. AF at one or more ambulatory visits was significantly less common in the AAIR group (4 (7.4%) v 14 (23.3%) in the DDDR-s group v 11 (17.5%) in the DDDR-l group; p = 0.03, log rank test). The risk of developing AF in the AAIR group compared with the DDDR-s group was significantly decreased after adjustment for brady-tachy syndrome in a Cox regression analysis (relative risk 0.27, 95% confidence interval (CI) 0.09 to 0.83, p = 0.02). The benefit of AAIR was highest among patients with brady-tachy syndrome. Brady-tachy syndrome and a thromboembolic event before pacemaker implantation were independent predictors of thromboembolism during follow up (relative risk 7.5, 95% CI 1.6 to 36.2, p = 0.01, and relative risk 4.7, 95% CI 1.2 to 17.9, p = 0.02, respectively). CONCLUSIONS: During a mean follow up of 2.9 years AAIR was associated with significantly less AF. The beneficial effect of AAIR was still significant after adjustment for brady-tachy syndrome. Brady-tachy syndrome was associated with an increased risk of thromboembolism.

Adult↗

PubMed2001

Serum hepatocyte growth factor levels in patients with chronic renal disease--effect of GFR and pathogenesis.

UNLABELLED: Hepatocyte growth factor (HGF) is a growth-promoting peptide that appears to act in a renotropic and nephroprotective manner during acute renal damage. Recent studies suggest that HGF is also of importance in chronic renal diseases. The serum HGF level is correlated with serum creatinine, and it has been suggested that glomerular and tubular diseases affect serum HGF differently. In the present study. levels of serum HGF were determined and correlated to glomerular filtration rate (GFR) in 118 patients with various chronic renal diseases. GFR was determined by 99mTc-DTPA clearance, and the GFR values were evenly distributed in the interval 5-155 mL/min/1.73 m2. Serum HGF levels increased slightly with decreasing GFR: the Pearson correlation coefficient being 0.49 (p<0.0001). In 21 additional patients with end-stage renal disease treated with continuous ambulatory peritoneal dialysis, there was a more marked increase in the serum levels of HGF. The effect of glomerular and tubular diseases on serum HGF was examined by comparing the HGF levels in two groups of patients with similar GFR values: 57 patients with mainly glomerular disorders (diabetic nephropathy with micro- or macroalbuminuria or glomerulonephritis) and 14 patients with mainly tubular disorders (polycystic kidney disease). There was no significant difference between the HGF levels of the two groups (p=0.30). IN CONCLUSION: Serum HGF levels are correlated with GFR (for GFR > or = 5 mL/min/1.73 m2) in patients with chronic renal diseases, and glomerular and tubular disorders seem to affect the HGF level similarly.

Adult↗

PubMed2001

Relation of left ventricular geometry and function to systemic hemodynamics in hypertension: the LIFE Study. Losartan Intervention For Endpoint Reduction in Hypertension Study.

OBJECTIVES: To clarify the relations of systemic hemodynamics to left ventricular (LV) geometric patterns in patients with moderate hypertension and target organ damage. BACKGROUND: LV geometry stratifies risk in hypertension, but relations of LV geometry to systemic hemodynamic patterns in moderately severe hypertension have not been fully elucidated. DESIGN: Cross-sectional case-control study. SETTING: Baseline findings in the echocardiographic substudy of the Losartan Intervention For Endpoint Reduction in Hypertension Study (LIFE) and in a normotensive reference group. PATIENTS/PARTICIPANTS: Nine hundred and sixty-four patients with Stage I-II hypertension and LV hypertrophy by Cornell voltage duration criteria ((SV3 + RaVL [+ 6 mm in women]) x QRS > 2440 mm x ms) or modified Sokolow- Lyon voltage criteria (SV1 + RV5/RV6 > 38 mm), and 366 apparently normal adults. INTERVENTIONS: None. METHODS: Two-dimensional and Doppler echocardiograms were used to classify hypertensive patients into groups with normal geometry, concentric remodelling and concentric and eccentric hypertrophy, and to measure stroke volume (SV), cardiac output, peripheral resistance and pulse pressure/SV as a measure of arterial stiffness. Comparisons were adjusted for covariates by general linear model with the Sidak post-hoc test RESULTS: Mean SV was higher in patients with eccentric hypertrophy (83 ml/beat) and lower with concentric remodeling (68 ml/beat) than in normal adults (73 ml/ beat). Cardiac output was highest in patients with eccentric LV hypertrophy and lower with concentric remodeling than eccentric hypertrophy; mean pressure and peripheral resistance were equally high in all hypertensive subgroups, whereas pulse pressure/SV was most elevated (by a mean of 47% versus reference subjects) with concentric remodeling and least so (mean + 15%) with eccentric hypertrophy. In multivariate analysis (Multiple R + 0.68), LV mass was independently related to higher systolic pressure, older age, SV, male gender and body mass index (all P< 0.001). Relative wall thickness was independently related (Multiple R + 0.50) to older age, higher systolic pressure, lower SV (all P< 0.001) and higher body mass index (P + 0.007). SV and cardiac output were lower in patients with low stress-corrected midwall shortening. CONCLUSION: In patients with moderate hypertension and ECG LV hypertrophy, the levels of SV and pulse pressure/ SV, are associated with, and may be stimuli to different LV geometric phenotypes.

Adult↗

PubMed2000

Diltiazem in acute myocardial infarction treated with thrombolytic agents: a randomised placebo-controlled trial. Incomplete Infarction Trial of European Research Collaborators Evaluating Prognosis post-Thrombolysis (INTERCEPT)

BACKGROUND: Diltiazem reduces non-fatal reinfarction and refractory ischaemia after non-Q-wave myocardial infarction, an acute coronary syndrome similar to the incomplete infarction that occurs after successful reperfusion. We postulated that this agent would reduce cardiac events in patients after acute myocardial infarction treated initially with thrombolytic agents-a clinical application previously unexplored with heart-rate-lowering calcium antagonists. METHODS: A prospective, randomised, double-blind, sequential trial was done in 874 patients with acute myocardial infarction, but without congestive heart failure, who first received thrombolytic agents. Patients received either 300 mg oral diltiazem once daily, or placebo, initiated within 36-96 h of infarct onset, and given for up to 6 months. The trial primary endpoint was the cumulative first event rate of cardiac death, non-fatal reinfarction, or refractory ischaemia. Additional prespecified endpoints included several composites of non-fatal cardiac events (non-fatal reinfarction combined with refractory ischaemia, all recurrent ischaemia, or the need for myocardial revascularisation). The diagnosis of ischaemia, whether refractory or recurrent, and the need for myocardial revascularisation, was always based on objective electrocardiographical evidence of ischaemia, either at rest or on exertion. RESULTS: For the trial primary endpoint, 131 events occurred in the 444 placebo patients and 97 events in the 430 diltiazem patients (hazard ratio 0.79; 95% CI, 0.61-1.02; p=0.07). For non-fatal cardiac events, diltiazem treatment was associated with a relative decrease (0.76; 0.58-1.00) in the combined event rate of non-fatal reinfarction and refractory ischaemia. There was a similar decrease in the composite non-fatal endpoints of non-fatal reinfarction combined with all recurrent ischaemia (0.80; 0.64-1.00) and non-fatal reinfarction combined with the need for myocardial revascularisation (0.67; 0.46-0.96). The need for myocardial revascularisation alone was significantly reduced by 42% (0.61; 0.39-0.96). No major safety issues were encountered. CONCLUSIONS: Diltiazem did not reduce the cumulative occurrence of cardiac death, non-fatal reinfarction, or refractory ischaemia during a 6-month follow-up, but did reduce all composite endpoints of non-fatal cardiac events, especially the need for myocardial revascularisation.

Calcium Channel Blockers↗

PubMed2000

Serum cystatin C as an endogenous parameter of the renal function in patients with normal to moderately impaired kidney function.

BACKGROUND: Cystatin C is a proteinase inhibitor with a low molecular weight. The serum levels of cystatin C are mainly dependent on glomerular filtration rate (GFR) making cystatin C an endogenous parameter of GFR. The aim of the study was to elucidate the applicability of serum cystatin C as a parameter of GFR in patients with normal to moderately impaired kidney function and to estimate a reference interval for serum cystatin C. PATIENTS AND METHODS: Forty-six patients (25 males and 21 females) aged 22 to 83 years with various kidney diseases and 250 blood donors (164 males and 86 females) aged 19 to 64 years were included. Cystatin C was measured by an automated particle-enhanced nephelometric immunoassay, serum creatinine by an enzymatic and by Jaffé method, urine creatinine by an enzymatic method, and GFR by 99mTc-DTPA clearance. RESULTS: Serum levels ofcystatin C and creatinine showed increments with decreasing values of 99mTc-DTPA clearance and a linear relationship was found between 99mTc-DTPA clearance and l/serum cystatin C, l/serum creatinine (enzymatic method), and creatinine clearance. Comparison of the non-parametric receiver-operating characteristic (ROC) plots for serum cystatin C (area under the curve (AUC) = 0.996; SE = 0.005), serum creatinine (enzymatic method) (AUC = 0.899; SE = 0.044), serum creatinine (Jaffé method) (AUC = 0.870; SE = 0.051), measured creatinine clearance (AUC = 0.959; SE = 0.025), and estimated creatinine clearance (0.950; SE = 0.029) revealed significant differences for serum cystatin C and serum creatinine (enzymatic and Jaffé method) (p values: 0.03 and 0.01). No significant differences were demonstrated between serum cystatin C and measured and estimated creatinine clearance (p value: 0.14 and 0.12). The non-parametric reference interval for serum cystatin C was calculated to be 0.51-1.02 mg/l (median: 0.79 mg/l; range: 0.33 - 1.07 mg/l). CONCLUSION: Serum cystatin C seems to be a better parameter of GFR than serum creatinine in adults with various types of kidney disease with normal to moderately impaired kidney function.

Adult↗

PubMed1997

Proximal tubular function in essential hypertensives on beta-blocker therapy with atenolol.

Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured during waterloading and constant infusion of [131I]hippuran and [125I]iothalamate in 24 mild to moderate essential hypertensive patients before and after 3.5 months treatment with atenolol. Clearances of sodium and potassium were measured 2-3 hours post-dosing and renal vascular resistance (RVR) and filtration fraction (FF) were calculated. Measurement of clearance of lithium (CLi) and uric acid (Curic acid) was employed to investigate specifically proximal tubular function. Beta-blockade with atenolol produced a borderline significant decrement in RPF but no change in GFR, RVR and FF. There was a significant reduction in CLi, fractional proximal escape of sodium and water, Curic acid and an increase in absolute proximal reabsorption of sodium, indicating an inhibition of proximal tubular function. The distal tubular parameters exhibited changes tending to normalize excretion of sodium, but not water. Changes in RVR were inversely related to changes in CLi and Curic acid, suggesting unopposed alfa-adrenergic stimulation to be implicated in the renal counterregulation at a proximal tubular site following long-term administration of atenolol in essential hypertension.

Adrenergic beta-Antagonists↗

PubMed1995

[Hypertensive crises. 1. Pathogenesis and symptomatology].

Hypertensive crisis is a medical emergency presenting with a severely increased blood pressure. The condition is associated with a state of increased vasoconstriction, coexisting hyponatriaemia and hypovolaemia. Besides the absolute level of blood pressure evidence of organ damage is also important in initial judgement of the case. Hypertensive crises are most commonly seen in younger patients with essential hypertension and in patients with secondary hypertension. It is unknown why a patient with hypertension suddenly develops a hypertensive crisis, but the renin-angiotension system seems to play an important role. Untreated, the disease will lead to irreversible end-organ damage. Hypertensive crises may be divided into "hypertensive emergencies" with evidence of severe new and/or progressive end-organ damage, requiring careful reduction of blood pressure within an hour, and "hypertensive urgencies" with no evidence of end-organ damage or complications where reduction of blood pressure to a safe level must be achieved within a few hours.

Critical Illness↗

PubMed1995

[Hypertensive crises. 2. Treatment].

Hypertensive crisis is a rare condition with increased blood pressure and evidence of new or progressive severe end-organ damage. The patients should be admitted to hospital, and the blood pressure reduced gradually. Blood pressure should not be normalized, but a reduction in mean arterial pressure of 20-25% or to a diastolic blood pressure > 100-110 mmHg should be achieved. Patients at particular risk for further complications are elderly, patients with hypovolaemia, renal insufficiency, ischaemic heart disease and patients with neurological deficits. The ideal antihypertensive drug for any form of hypertensive crisis does not exist. If the patient can cooperate with oral treatment, nifedipine may be used, usually administered as capsules of 10 mg orally, producing a rapid and safe reduction in blood pressure of 25% within 10-15 minutes with a maximal action after 30-60 minutes. The dose may be repeated after 30 minutes in case of insufficient blood pressure response. Hypotension is rare. Nifedipine in combination with nitroglycerine is of special benefit in hypertensive pulmonary oedema. In cases of treatment failure or if the patient cannot cooperate with oral treatment, the choice of drug lies between labetalol and sodium nitroprusside. Nitroprusside is administered as continuous intravenous infusion, the drug is safe to use and is recommended in conditions where reduction of blood pressure must be performed with extreme caution such as in cases of cerebral infarction and intracranial hemorrhage. Infusion of nitroprusside for more than 48-72 hours is inexpedient because the metabolites of nitroprusside need monitoring as well. Parenteral drug therapy with labetalol is more simple than treatment with nitroprusside, but at the same time somewhat more difficult to titrate. Nitroglycerine is very suitable in moderate hypertension and ischaemic heart disease, but in severe hypertension with heart disease nitroprusside is the treatment of choice. Loop diuretics should not be used as first-line drugs, but only in conditions with evidence of volume-overload. Patients with hypertensive crisis most often show volume depletion which is aggravated by loop diuretics, therefore they should not be used routinely. When the blood pressure has been stabilized, an oral antihypertensive drug should be started concomitantly to a gradual reduction of the initial parenteral drug therapy.

Antihypertensive Agents↗

PubMed1995

Silent myocardial ischaemia in untreated essential hypertensives.

In hypertension, hypertrophy of the left ventricle might enhance the risk of ischaemia because of an augmented oxygen demand and an insufficient oxygen supply. The aims of the study were to estimate the prevalence of silent ischaemia in a group of untreated hypertensives with Holter monitoring and 3 different stress tests, and to look for a possible association between the presence of ischaemia and the blood pressure level as well as the left ventricular mass. The prevalence of silent ischaemia was tested in a group of 34 untreated hypertensives by Holter monitoring and by bicycle ergometer test, hyperventilation and captopril tests. 68% of the patients exhibited silent ischaemic periods during Holter monitoring. There was a trend towards a higher 24-hour SBP and DBP level in patients with ischaemia (p < 0.05), in addition to a tendency towards a higher catecholamine excretion in patients with ischaemia (p < 0.05), and a higher left ventricular mass (NS). Silent ischaemic episodes during ergometer exercise test were found in 27%. Only 3% had ischaemia during hyperventilation and captopril tests. In conclusion, the prevalence of ischaemia during the various stress tests was low, whereas Holter monitoring revealed signs of silent ischaemia in a substantial proportion of the patients. Patients with ischaemia tended to present more severe degrees of hypertension.

Adult↗

PubMed1994

Normalization of resistance artery structure and left ventricular morphology with a perindopril-based regimen.

Twenty-five patients with newly diagnosed or poorly regulated essential hypertension were randomly selected from a larger group referred to hospital. Treatment was initiated with perindopril (4 to 8 mg od). If normotension was not achieved, isradipine (5 to 10 mg od) was added and, if necessary, hydralazine was added. Before treatment and at the end of a nine-month period of normotension (diastolic blood pressure less than 90 mmHg), 24 h blood pressure and echocardiographic measurements were performed and resistance artery structure was determined. Twenty age- and sex-matched normotensives were used as controls. During antihypertensive treatment, mean blood pressure was reduced from 128 +/- 11 to 103 +/- 6 mmHg. Left ventricular mass was reduced from 300 +/- 76 to 198 +/- 54 g. The media:lumen ratio of the resistance arteries decreased from 9.8 +/- 2.6% to 7.8 +/- 1.9%. Control subjects exhibited a media:lumen ratio of the same magnitude (7.9 +/- 2.0). Regression of left ventricular mass correlated significantly with regression of the media:lumen ratio with a coefficient of 0.59 (P < 0.05). Results indicate that a perindopril-based regimen is extremely efficient in normalizing resistance artery and cardiac ventricular structures within one year of treatment. The impact of these findings on the excess cardiovascular morbidity and mortality in arterial hypertension still remains to be demonstrated.

Antihypertensive Agents↗

PubMed1993

Proximal renal tubular pressure-natriuresis-relation in essential hypertensives following acute vasodilatation.

Blood pressure (BP) and excretory function including lithium clearance were investigated during water-loading and constant infusion of 131I-hippuran and 125I-iothalamate for measurement of renal haemodynamics in 8 untreated essential hypertensives (mean BP +/- SD: 169 +/- 14/107 +/- 6 mmHg) before and after vasodilatation with an i.v. bolus of the potassium-channel opener, pinacidil, 0.01 mg/kg. Systolic BP (-7 +/- 4%; p < 0.05) and diastolic BP (-13 +/- 8%; p < 0.01) decreased significantly and heart rate increased (11 +/- 8%; p < 0.01). Clearance (C) of lithium, sodium, urinary flow rate, potassium and absolute distal reabsorption of sodium all fell significantly. The changes of these variables were significantly correlated with the fall in BP (CLi:r = 0.92, CNa: r = 0.85, V: r = 0.81, CK:r = 0.84), despite no significant changes in renal haemodynamic parameters: glomerular filtration rate, renal plasma flow and renal vascular resistance. A proximal tubular effect was also indicated by a fall in Curic acid and fractional Curic acid. In conclusion, vasodilatation in essential hypertensives following administration of the potassium channel opener, pinacidil, induces a fall in blood pressure with a corresponding fall in fractional proximal tubular excretion of sodium and output of sodium and water from proximal to distal tubular segments, proposing an acute proximal tubular pressure-natriuresis relation.

Adult↗

PubMed1992

[Cardiovascular changes in arterial hypertension].

In untreated essential hypertension cardiovascular structural changes will develop after some time. In arteries and arterioles, thickening and reduced compliance of the vascular wall is noted and in the left ventricle, myocardial hypertrophy. Both types of changes will enhance the risk of ischemia and of developing cardiac complications, i.e. coronary heart disease, myocardial infarction and heart failure. Methods for measurement of vascular and cardiac hypertrophy are reviewed and the value of echo-cardiographic evaluation of the hypertensive patient is stressed.

Coronary Disease↗

PubMed1992

[Regression of hypertensive cardiovascular changes during treatment with antihypertensive ddrugs].

Antihypertensive medical treatment may induce regression of hypertensive structural cardiovascular changes after a period of time: Hypertrophy of the left ventricle and of the smooth muscle layer in the resistance vessels. In this paper, we refer to significant human studies, published during the last decade, concerning the degree of regression of these presumably secondary structural changes, resulting from antihypertensive treatment. It has been shown that most antihypertensive regimens in common use, calcium antagonists, ACE inhibitors and most beta blockers, but not diuretics and nonspecific vasodilators, are, when effective in lowering blood pressure, also capable of inducing a probably complete regression of the cardiac hypertrophy. However, complete regression of the vascular changes has not been shown.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1992

Alpha-adrenoceptor blockade in patients with mild to moderate hypertension: long-term renal effects of doxazosin.

Using constant infusion technique and a water-loading procedure, we investigated renal hemodynamic and excretional variables in 15 essential hypertensive patients [diastolic blood pressure (DBP) 102 +/- 10 mm Hg] after 3 weeks of placebo and after 16 weeks of treatment with a postjunctional alpha 1-adrenoceptor-antagonist, doxazosin (1-16 mg) once daily. A minor decrease in supine DBP (p less than 0.05) but no significant changes in systolic BP (SBP) and heart rate (HR) were observed. No significant changes were noted in glomerular filtration rate (GFR), renal plasma flow (RPF), and renal vascular resistance (RVR). The mean renal excretion rate of sodium, potassium, uric acid, and albumin for the entire group was unaffected by the treatment, but the individual changes in sodium clearance correlated significantly with changes in mean BP (r = 0.64, n = 15, p less than 0.05). Six patients showed an increase in sodium excretion after treatment, whereas nine showed a decrease. No decrease in mean body weight was noted, but the BP reduction after 5 months of treatment correlated significantly with the changes in body weight (r = 0.62, n = 15, p less than 0.01). The results indicate that long-term treatment with doxazosin had no deleterious effect on renal function, but the effects on BP were rather modest. The individual BP response is probably determined by the degree of fluid retention even if an intact pressure-natriuresis relationship could still be demonstrated during chronic therapy.

Adrenergic alpha-Antagonists↗

PubMed1992

Combined actions of isradipine and captopril on renal function in hypertension.

The object of this study was to test the hypothesis that the natriuretic and uricosuric effect of calcium-entry blockers could be mediated through antagonism of angiotensin II dependent intrarenal mechanisms. The antihypertensive efficacy, haemodynamic and excretional effects of superimposed calcium blockade with isradipine were investigated in seven hypertensives with unsatisfactorally controlled blood pressure with captopril 50 mg twice daily. Glomerular filtration rate (GFR) and renal plasma flow (RPF), clearances (C) of sodium (Na), potassium (K), uric acid (UA) and lithium (Li), were measured before and after a low-dose bolus of isradipine, i.v. Subsequently, measurements were repeated during constant i.v. infusion of a higher dose with definite systemic haemodynamic effects. After 4 months of combined treatment with isradipine and captopril renal investigations were carried out again. The low isradipine dose induced a slight but statistically significant increment in CNa (22% +/- 28) and heart rate (4% +/- 4), whereas no other variables changed significantly. Infusion of the high isradipine dose caused a pronounced fall in renal vascular resistance (27% +/- 14), systolic (8% +/- 2) and diastolic blood pressure (17% +/- 5). RPF increased significantly (15% +/- 18) whereas no changes were noted in GFR, filtration fraction and urinary albumin excretion rate. In spite of the pronounced fall in BP during the high dose infusion, significant increments in natriuresis (91% +/- 63) and diuresis (41% +/- 27) were induced. The natriuresis was caused by a proximal tubular action as indicated by increased CLi and CLi/GFR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

[Amlodipine].

Explore the source record for details and available documents.

Amlodipine↗

PubMed1990

[Calcium antagonists: an antihypertensive alternative].

From a pathophysiological point of view, antihypertensive therapy with a vasodilator is rational. However, since traditional vasodilators, such as hydralazine, may cause retention of sodium and water, tachycardia and excessive stimulation of the renin-angiotensin-aldosterone system, they are not suitable for monotherapy. The Ca-antagonists include a number of drugs with quite different chemical structures. Ca-antagonists are powerful antihypertensive agents. This effect is due primarily to vasodilation caused by the interference with the excitation-contraction coupling in peripheral resistance vessels. All Ca-antagonists possess a natriuretic effect which apparently counteracts the sodium and water retention that vasodilation per se entails. Ca-antagonists cause no (verapamil) or a transient tachycardia (dihydropyridines) and they only cause a moderate and transient increase in plasma concentrations of renin and angiotensin II, whereas plasma aldosterone concentration is unaffected. Ca-antagonists have no metabolic side effects and in general the frequency of side effects is relatively low. Therefore, it is suggested that Ca-antagonists should be considered as possible first-choice agents along with diuretics, beta-blockers and angiotensin converting-enzyme inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1989

Long-term effects of isradipine on blood pressure and renal function.

The hemodynamic and renal effects of isradipine were investigated in 10 hypertensive patients treated for 3.5 months and in a further nine patients treated for two years. Both groups achieved significant and sustained reductions in systolic blood pressure/diastolic blood pressure (-15 percent/-12 percent and -15 percent/-20 percent, respectively; p less than 0.001). Renal parameters were investigated two to three hours after the morning dose of isradipine, using a water-loading procedure. After 3.5 months of treatment, the glomerular filtration rate and renal plasma flow showed small increases (+6 percent and +9 percent, respectively, p less than 0.05), whereas, after two years, these changes were no longer present (+4 percent and 0 percent). Clearance of sodium and uric acid was increased by 40 percent (p less than 0.01) and 21 percent (p less than 0.01), respectively, after 3.5 months, and by 45 percent (p less than 0.05) and 23 percent (p less than 0.01), respectively, after two years. Lithium clearance studies revealed the natriuretic effect to be located in the proximal tubule. After 3.5 months, a significant relationship was found between the blood pressure response and the change in sodium excretion, but this relationship also was no longer present after two years. In conclusion, because of a maintained blood pressure-lowering effect while preserving renal function, and sustained natriuretic and uricosuric actions, isradipine can be considered a promising agent in the long-term treatment of arterial hypertension.

Antihypertensive Agents↗