Effects of calcium antagonists on renal function.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
J H Bauer
Publications and source records attributed to J H Bauer.
Effect of nifedipine on renal function in patients with essential hypertension.
Twenty-six essential hypertensive patients were entered into a protocol to assess the blood pressure and renal effects of the dihydropyridine calcium antagonist nifedipine (30-120 mg/day given in divided doses) administered for 4 weeks. Nifedipine monotherapy effectively lowered blood pressure in 73% of the patients. Glomerular filtration rate and effective renal plasma flow were increased 13.3 and 19.6%, respectively. The filtration fraction and urinary albumin excretion remained unchanged. Renal vascular resistance was markedly reduced (25.2%). Changes observed in renal function were independent of the patients' initial glomerular filtration rate. Furthermore, there was no correlation between the systemic and renal effects of nifedipine monotherapy. Patients with a poor systemic blood pressure response exhibited increases in both glomerular filtration rate (+13%) and effective renal plasma flow (+20%), changes comparable with increases in glomerular filtration rate (+13%) and effective renal plasma flow (+19%) observed in patients achieving a goal blood pressure response (diastolic blood pressure less than or equal to 90 mm Hg, or a greater than or equal to 10 mm Hg decrease in diastolic blood pressure, or both). These results suggest that nifedipine monotherapy has the potential to improve renal function abnormalities encountered in the essential hypertensive state independently of its effect on systemic blood pressure.
Adult↗
Renal protective effect of long term antihypertensive therapy with enalapril.
This review focuses on recent human studies with the angiotensin-converting enzyme (ACE) inhibitor enalapril, prescribed either alone or in combination with a diuretic, to patients with essential hypertension and to patients with hypertension associated with moderate to severe renal parenchymal disease. Data suggest that enalapril therapy may provide a renal protective effect. In addition to lowering and controlling systemic arterial blood pressure, enalapril therapy is associated with stabilisation of, and/or improvement in effective renal plasma flow, glomerular filtration rate (GFR) and urinary protein excretion. Such renal protective effects are probably mediated by normalisation of both the systemic arterial blood pressure and intraglomerular capillary hydraulic pressure, and by an increase in the glomerular ultrafiltration coefficient. Drug therapy enabling control of both systemic and glomerular hypertension may prevent hypertensive renal end-organ damage and attenuate the natural progression of renal parenchymal disease.
Antihypertensive Agents↗
Efficacy, electrocardiographic and renal effects of intravenous diltiazem for essential hypertension.
The acute systemic blood pressure, electrocardiographic and renal function responses to an intravenous bolus infusion of diltiazem (0.2 to 0.5 mg/kg) were evaluated in 18 subjects with mild to moderate essential hypertension. Although a significant blood pressure response occurred within 5 minutes, blood pressure returned to pretreatment levels within 1 to 3 hours. After drug infusion, a variety of rhythm and conduction disturbances were noted; the most important were transient prolongation of the PR Interval (first-degree atrioventricular block), a single episode of second-degree atrioventricular block (Mobitz I) associated with T-wave inversion and a transient episode of junctional escape rhythm and atrioventricular dissociation. Intravenous diltiazem had no consistent effect on glomerular filtration rate or effective renal plasma flow. Natriuresis and kaliuresis were observed only at the highest infusion dose. It is concluded that an alternative dosing regimen will be required if intravenous diltiazem is to be used safely and effectively to control blood pressure in patients with hypertensive disease.
Blood Pressure↗
High-performance liquid chromatographic-radioimmunoassay method for the measurement of angiotensin II peptides in human plasma.
A highly selective high-performance liquid chromatographic-radioimmunoassay method for the measurement of individual endogenous angiotensin peptides in human plasma is described. This method allows the complete resolution of the immunoreactive angiotensin II peptides. We have also measured the angiotensin peptide levels and compared them in both pooled and individual human plasma. The effects of inhibition of angiotensin-converting enzyme on the angiotensin peptide levels have also been observed in a patient with renovascular hypertension with the plasma angiotensin II level being reduced greater than seven-fold. This new methodology was validated by recovery experiments in plasma over a range of physiological levels using two methods of detection, radioimmunoassay and liquid scintillation counting. Consistent recoveries near 80% have been achieved for each peptide in plasma at concentrations over a physiological range. The described method enables the direct measurement of the circulating angiotensin peptides and the elucidation of their specific roles in physiological and disease states.
Angiotensin II↗
Short- and long-term effects of calcium entry blockers on the kidney.
The renal effects of the calcium entry-blocking drugs diltiazem, nifedipine, nitrendipine, nicardipine and verapamil are reviewed. Although nifedipine may acutely increase plasma renin activity, most of the calcium entry blockers have no sustained effect on any of the components of the renin-angiotensin-aldosterone system. Although all of the calcium entry blockers effectively lower blood pressure, none adversely affects renal function: Glomerular filtration rate and effective renal plasma flow are maintained. Diltiazem may increase glomerular filtration rate via attenuation of the intrarenal effects of angiotensin II or norepinephrine. Although all of the calcium entry blockers acutely increase salt and water excretion, most of the calcium entry blockers have no clinically sustained effect on salt and water excretion; serum electrolytes, urinary sodium and potassium excretion, body fluid composition and body weight are usually unchanged. Calcium entry blockers can be expected to assume a prominent role in the treatment of hypertension because of their ability to lower blood pressure while preserving renal perfusion and function.
Animals↗
The acute and chronic effects of betaxolol on blood pressure, renin-aldosterone, and renal function in essential hypertension.
The effects of betaxolol, a long-acting, lipid-soluble, cardioselective, beta-adrenergic antagonist on renal function have not been previously reported. The present study was designed to prospectively assess the acute and chronic antihypertensive, humoral, and renal response to betaxolol, administered once daily, to patients with essential hypertension. After a four-week placebo run-in period, 13 patients with essential hypertension were treated with betaxolol monotherapy for a total of eight months. Results indicate that blood pressure is reduced, and renal function remains stable. These findings are consistent with previous observations with other beta-adrenergic antagonists.
Adrenergic beta-Antagonists↗
Renal protective effects of calcium antagonists?
Explore the source record for details and available documents.
Calcium Channel Blockers↗
Long-term renal effects of diltiazem in essential hypertension.
Eighteen hypertensive patients underwent short-term (8 weeks) and long-term (6 months) assessment of renal function and body fluid composition following diltiazem monotherapy (240 to 480 mg/day). Diltiazem monotherapy effectively lowered blood pressure in 60% of patients at 8 weeks. In 12 of the 18 patients continued on diltiazem monotherapy for 6 months, good control of blood pressure was sustained. Glomerular filtration rate, effective renal plasma flow, filtration fraction, and renal vascular resistance were unchanged throughout the protocol period. In individuals with pretreatment glomerular filtration rates less than or equal to 80 ml/min/1.73m2, diltiazem monotherapy showed both short-term and long-term improvement in glomerular filtration rate (62%) and effective renal plasma flow (34%). Filtration fraction was unchanged, suggesting that the changes in glomerular filtration rate might be related to the attenuated intrarenal effects of angiotensin II and/or norepinephrine. No long-term effect was seen on salt and water excretion or body fluid composition.
Blood Pressure↗
Intravenous energy and amino acids in the preterm newborn infant: effects on metabolic rate and potential mechanisms of action.
The effects of intravenously administered amino acids and of varying amounts of energy on metabolic rate were studied and potential mechanisms examined in 19 healthy 4- to 6-day-old preterm (30 to 32 weeks gestation) infants. The infants were randomized to three groups. Group 1 (n = 6) received nonprotein energy 38 kcal/kg/d; group 2 (n = 5), 64 kcal/kg/d; and group 3 (n = 8), 64 kcal/kg/d plus 1 to 2 g/kg/d crystalline amino acids. Thirty-six hours after beginning the infusion, oxygen consumption (VO2) was measured by indirect calorimetry for 5 to 6 hours. Simultaneously, urine was collected for urinary norepinephrine excretion, which was determined using liquid chromatography with electrochemical detection. Serum thyroxine (T4) and triiodothyronine (T3) concentrations were determined by radioimmunoassay. Group 1 had lower VO2 and urinary norepinephrine excretion than did groups 2 and 3, which did not differ. T4 and T3 were not different among the three groups. The demonstrated simultaneous changes in VO2 and norepinephrine excretion with varying energy intakes independent of age supports energy intake as a modulator of the sympathetic nervous system, which in turn controls metabolic rate. Moderate amounts of intravenously administered amino acids do not appear to play an active role in this process; nor do they alter T3 and T4 valves. When VO2 increased with increasing energy intake, T3 and T4 were unaffected, supporting a passive role for thyroid hormones in diet-induced thermogenesis.
Amino Acids↗
A comparison of betaxolol and nadolol on renal function in essential hypertension.
Betaxolol, a beta 1-selective adrenergic antagonist, and nadolol, a nonselective beta-adrenergic antagonist are both potent long-acting antihypertensive drugs. The effects of betaxolol on renal function have not been reported. The effects of nadolol on renal function are controversial. The current randomized double-blind study was designed to compare the effects of betaxolol and nadolol on glomerular filtration rate, assessed by creatinine and inulin clearances, and renal hemodynamics, assessed by p-aminohippurate clearance. Following a 4-week placebo run-in period, 15 patients with essential hypertension were randomized to a mean dose of 22 mg betaxolol for 12 weeks, and 12 patients with essential hypertension were randomized to a mean dose of 103 mg nadolol for 12 weeks. Results indicate that neither drug produced a clinically relevant effect on renal function. These findings are consistent with previously reported observations with other beta-adrenergic blocking drugs. We conclude that neither of the beta-adrenergic antagonists, betaxolol or nadolol, convey a specific renal pharmacologic advantage; both are equally efficacious and safe in the treatment of mild-to-moderate essential hypertension.
Betaxolol↗
Amlodipine therapy corrects renal abnormalities encountered in the hypertensive state.
Calcium antagonists may increase glomerular filtration rate and renal plasma flow by antagonizing the intrarenal effects of angiotensin II and/or norepinephrine. We prospectively studied the effects of amlodipine, a once-a-day dihydropyridine calcium channel antagonist, in 19 patients with essential hypertension. Studies were performed after 4 weeks of placebo and 6 weeks of amlodipine therapy, and included the assessment of systolic and diastolic BP, renal clearances of inulin and p-aminohippurate, and determination of body fluid composition. Systolic and diastolic BPs were reduced following 6 weeks of amlodipine monotherapy. In spite of significant decreases in mean arterial pressure, there were increases in inulin clearance (+ 13%), and p-aminohippurate clearance (+ 19%). Filtration fraction was not changed. Renal vascular resistance was decreased (-25%). Total blood volume, extracellular fluid volume, and total body water and body weight were not changed. We conclude that amlodipine therapy has the potential to reverse renal abnormalities encountered in the hypertensive state.
Adult↗
Renal protective effect of strict blood pressure control with enalapril therapy.
The effect of strict blood pressure control on progression of renal disease in patients with essential hypertension has not been well defined. We have followed prospectively for three years 23 patients with essential hypertension. Blood pressure was well controlled on either enalapril or enalapril-hydrochlorothiazide therapy. Yearly assessment of renal function revealed no change in glomerular filtration rate as assessed by creatinine or inulin clearance, and a sustained 17% increase in effective renal plasma flow. In patients with moderately impaired renal function (inulin clearance less than or equal to 1.33 mL/s [80 mL/min]), there was a first-year 50% increase in inulin clearance, and a 33% increase in inulin clearance at year three. In these patients, there was a 39% first-year increase in effective renal plasma flow, which was sustained at year three. Filtration fraction and urinary protein excretion were unchanged. These results suggest that long-term blood pressure control with the angiotensin-converting enzyme inhibitor enalapril or enalapril-hydrochlorothiazide is associated with preservation and/or improvement in renal function.
Blood Pressure↗
Total and split renal function in patients with renovascular hypertension: effects of angiotensin-converting enzyme inhibition.
Thirteen subjects with documented renovascular hypertension receiving chronic (greater than 1 month) therapy with an angiotensin-converting enzyme inhibitor (enalapril or captopril) underwent total and split renal function studies. Total glomerular filtration rate as assessed by inulin clearance was similar to that determined by radionuclide technique. Total effective renal plasma flow as assessed by p-aminohippurate clearance was lower than that determined by radionuclide technique. The glomerular filtration rate and effective renal plasma flow assessed by radionuclide technique of the stenotic kidney was comparatively lower than that of the non-stenotic kidney. No subject demonstrated complete loss of filtration or perfusion of the stenotic kidney. Five of six patients studied prospectively for 2 years have demonstrated stability of total renal function; the sixth patient, having a functional solitary stenotic kidney, has demonstrated stability of function following an initial abrupt decline in glomerular filtration rate and effective renal plasma flow. These results suggest that chronic angiotensin-converting enzyme inhibition therapy is not generally associated with near total absence of filtration of the stenotic kidney as has been suggested previously. Angiotensin-converting enzyme inhibitors may be safely and effectively utilized in the treatment of renovascular hypertension.
Adult↗
Angiotensin II potentiates the vasoconstrictive effect of norepinephrine in normotensive and hypertensive man.
The renin-angiotensin system may effect blood pressure regulation by enhancing sympathetic activity. Angiotensin II given in subpressor doses has been shown to enhance the vasoconstrictive effect of norepinephrine in several animal models. However, the effects of subpressor doses of angiotensin II on the vasoconstrictor effects of norepinephrine have not been reported in humans. We found that angiotensin II, given in subpressor doses, potentiates the vascular response of norepinephrine in normotensive and hypertensive male subjects. These results demonstrate the important inter-relationship of the renin-angiotensin system to the sympathetic nervous system in normal and essential hypertensive man.
Adult↗
The role of calcium entry blockers in hypertensive emergencies.
This review focuses on the potential use of the calcium antagonists diltiazem, nifedipine, and verapamil in the treatment of hypertensive emergencies. Prompt reduction of blood pressure can be achieved after either intravenous administration of diltiazem or verapamil or sublingual/oral administration of nifedipine. Effects on cardiac hemodynamics with these drugs are variable. Effects on the kidney are predictable; administration is associated with prompt diuresis and natriuresis. Effects on the cerebral circulation are more complex; although cerebral vasodilation may occur, the potential exists for uneven cerebral perfusion and an increase in intracranial pressure. Precipitous decreases in mean arterial pressure may decrease cerebral blood flow below the lower limit of autoregulation, inducing cerebral ischemia. Because of the complex interaction of these drugs on the heart, kidney, and brain, short-term therapy should be instituted only in the hospital setting, with appropriate supervision and hemodynamic monitoring.
Antihypertensive Agents↗
Renal effects of angiotensin converting enzyme inhibitors in hypertension.
This review focuses on the renal effects of the angiotensin converting enzyme inhibitors, captopril and enalapril. Emphasis is placed on the renal response to these drugs in patients with primary essential hypertension, and in hypertension accompanying renal parenchymal disease. Specifically reviewed are the renal function and hemodynamic, salt and water, body fluid composition, and urinary protein excretion responses. The interruption of the renin-angiotensin-aldosterone axis has the potential to produce a variety of favorable renal responses, including reduction of renal vascular resistance, enhancement of renal blood flow, enhancement of glomerular filtration rate, acute natriuresis, sustained diuresis, and a decrease in urinary protein excretion. Data in support of these potential renal perturbations are presented and discussed. The results suggest that the angiotensin converting enzyme inhibitors are important therapeutic agents in the treatment of hypertensive disease, in that they may modify pathophysiologic renal abnormalities encountered in this disease state.
Angiotensin-Converting Enzyme Inhibitors↗
The amount of sodium removed by hemodialysis.
The amount of sodium removed by hemodialysis was estimated, without using radioisotopes, as the change in total osmotically active cations, which is the product of the serum sodium concentration and urea-space. The extracellular and total body fluid volumes were measured using 35SO4 and 3H2O, respectively, in five stable hemodialysis patients under four different conditions. Urea-space determined, based on urea kinetics, was consistent with total body fluid volume measured by 3H2O. The amount of sodium removal, estimated as the change in the product of the serum (Na+) and urea-space, was equal to the change in the sodium content, which is the product of the serum (Na+) and extracellular fluid volume measured by 35SO4. Sodium removal may be divided into two components, diffusion and ultrafiltration.
Blood↗