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Biomedical subjects

J H Bauer

Publications and source records attributed to J H Bauer.

At least 73 records · Page 4Linked to original sources
PubMed1986

Humoral effects of long-term oral enalapril therapy.

Twenty-seven subjects with essential hypertension were prospectively followed for a minimum of 100 weeks, receiving either enalapril monotherapy or enalapril and hydrochlorothiazide combination therapy. Blood pressure and the renin-angiotensin-aldosterone system were assessed following 4 weeks of placebo therapy, and 56 and 96 weeks of maintenance drug therapy. Blood pressure was well controlled with either form of therapy. Plasma renin activity remained stimulated following both long-term monotherapy and combination therapy. However, immunoreactive plasma angiotensin II concentration was not suppressed following either long-term monotherapy or combination therapy. Similarly, plasma aldosterone concentration was not suppressed following either form of therapy; indeed, combination therapy was associated with stimulation of plasma aldosterone concentration. We conclude that enalapril monotherapy or enalapril/hydrochlorothiazide therapy was effective in controlling blood pressure, but that long-term blood pressure control must be related to an angiotensin II independent antihypertensive mechanism.

Administration, Oral↗
PubMed1986

Renal function and hemodynamics during treatment with enalapril in primary hypertension.

Thirty-nine hypertensive patients were entered into a randomized, double-blind protocol to assess the effects of enalapril (10-20 mg b.i.d.), or combined enalapril (10-20 mg b.i.d.) and hydrochlorothiazide (25-50 mg b.i.d.) therapy on renal function and hemodynamics. Enalapril, either alone or in combination with hydrochlorothiazide, effectively controlled blood pressure. In patients with an initial inulin clearance less than or equal to 80 ml/min/1.73 m2, inulin and p-aminohippurate clearances were markedly improved toward normal following either drug therapy. The filtration fraction was either unchanged (monotherapy) or increased (combination therapy), suggesting a direct glomerular effect of angiotensin-converting enzyme inhibition. Renal vascular resistance was decreased in all patients. These observations suggest that enalapril, either alone or in combination with a diuretic, has the potential to reverse renal function abnormalities encountered in the hypertensive state.

Double-Blind Method↗
PubMed1986

Renal effects of diltiazem in primary hypertension.

Although the calcium channel blocker diltiazem has been shown to be an effective antihypertensive agent, its effect on renal function, salt and water excretion, and body fluid composition has not been well characterized in patients with primary hypertension. Therefore, these parameters were prospectively studied in 18 subjects with primary hypertension after placebo and 8 weeks of diltiazem monotherapy. Diltiazem monotherapy was confirmed to be an effective antihypertensive agent. Although mean arterial pressure was reduced from 121 to 108 mm Hg, diltiazem had no overall effect on glomerular filtration rate, renal plasma blood flow, salt and water excretion, or body fluid composition. Renal vascular resistance, however, was decreased. In subjects with pretreatment glomerular filtration rates of 80 ml/min/1.73 m2 or less, diltiazem therapy was associated with marked improvement in glomerular filtration rate (48%) and effective renal plasma flow (36%). Since the filtration fraction was unchanged, changes in glomerular filtration rate may have been related to the attenuated intrarenal effects of angiotensin II or norepinephrine, or both.

Benzazepines↗
PubMed1986

Use of the converting enzyme inhibitor enalapril in renovascular hypertension. Effect on blood pressure, renal function, and the renin-angiotensin-aldosterone system.

Thirteen patients were entered into a protocol to assess the safety and efficacy of enalapril (MK 421), 5 to 20 mg b.i.d., and hydrochlorothiazide, 50 to 100 mg daily, for the treatment of renovascular hypertension. Specifically monitored were the effects of therapy on blood pressure and pulse, renal function, and the renin-angiotensin-aldosterone axis. Enalapril and hydrochlorothiazide therapy produced excellent control of blood pressure with no adverse side effects. After approximately 8 weeks of therapy, renal vascular resistance was decreased and no adverse effects on glomerular filtration rate or renal blood flow were noted, except in one patient with a functional unilateral stenotic kidney. Patients receiving enalapril and hydrochlorothiazide showed stimulation of plasma renin activity and suppression of plasma angiotensin II, although the initial degree of suppression was not sustained in all patients during prolonged therapy. Although plasma aldosterone concentration was initially suppressed, the degree of suppression was not sustained. Nine patients have been followed for an additional 6 months; none have experienced further progression of renal disease, as assessed by repeated measurements of glomerular filtration and effective renal plasma flow. These results suggest that combined enalapril and hydrochlorothiazide therapy is safe and effective in the medical management of renovascular hypertension and that blood pressure control may be achieved in the absence of sustained interruption of the renin-angiotensin-aldosterone system.

Angiography↗
PubMed1986

Long-term effects of enalapril monotherapy and enalapril/hydrochlorothiazide combination therapy on blood pressure, renal function, and body fluid composition.

Enalapril, a potent long-acting angiotensin-converting enzyme inhibitor, was prescribed either alone (n = 9) or in combination (n = 20) with hydrochlorothiazide for 96 weeks in essential hypertensive subjects. Blood pressure was well controlled following both monotherapy or combination therapy. Plasma renin activity was stimulated in all subjects; plasma aldosterone concentration was stimulated only in subjects receiving combination therapy. Glomerular filtration rate (assessed by inulin clearance) was unchanged in subjects with initial clearances greater than 80 ml/min/1.73 m2 but was significantly improved (55%) following either form of therapy in subjects with initial clearances less than or equal to 80 ml/min/1.73 m2. Neither monotherapy nor combination therapy adversely affected 24-hour urinary protein excretion, sodium excretion, or body fluid composition. These results suggest that enalapril, either alone or in combination with hydrochlorothiazide, is effective therapy for mild to moderate hypertension. There are no adverse effect on renal function; indeed, enalapril has the capability of improving renal function in those subjects whose renal function was initially impaired from long-standing hypertension.

Adult↗
PubMed1986

Effect of enalapril in subjects with hypertension associated with moderate to severe renal dysfunction.

The purpose of this study was to define the effect of the angiotensin-converting enzyme inhibitor, enalapril maleate, on blood pressure, renal function, protein excretion, and potassium homeostasis in patients with hypertension associated with moderate to severe renal dysfunction. Nine patients, having an initial inulin clearance between 9 and 48 mL/min/1.73 m2, were treated with enalapril monotherapy (n = 6) or enalapril/furosemide (n = 3) combination therapy. Systolic and diastolic blood pressures were well controlled. Supine plasma renin activity was stimulated; the supine plasma aldosterone level was suppressed, with a resultant increase in the serum potassium level. Clinical hyperkalemia was not observed. Glomerular filtration rate, assessed by inulin and creatinine clearances, was not significantly changed. Effective renal plasma flow, assessed by paraaminohippurate clearance was significantly increased, with a resultant decrease in filtration fraction. Importantly, urinary protein excretion was markedly reduced. These results suggest that enalapril therapy produces efferent arteriolar dilitation with preservation of the glomerular filtration rate. Enalapril therapy may also blunt the effects of angiotensin II on transglomerular passage of protein, as demonstrated by reduced proteinuria. These findings suggest that interruption of the renin-angiotensin system in patients with preexisting renal disease may have renal protective effects.

Adult↗
PubMed1986

Enalaprilat: an intravenous substitute for oral enalapril therapy. Humoral and pharmacokinetic effects.

Thirteen subjects with essential hypertension controlled on oral enalapril (20 mg/day) therapy were entered into a protocol to assess serially 24-hour blood pressure, the renin-angiotensin-aldosterone system, angiotensin-converting enzyme activity, and plasma and urine enalaprilat drug levels, following both chronic oral administration of enalapril and its replacement with intravenous enalaprilat. Results indicate that systolic and diastolic blood pressures remain well controlled following cessation of oral enalapril and replacement with intravenous enalaprilat. Enalaprilat drug levels, following oral enalapril and intravenous enalaprilat, remained above the therapeutic levels required for angiotensin-converting enzyme inhibition. However, therapeutic enalaprilat levels can probably be achieved with one fourth of the total cumulative dose of enalapril, administered as enalaprilat at 6-hour intervals. Intravenous enalaprilat stimulated plasma renin activity and decreased immunoreactive plasma angiotensin II and plasma aldosterone concentrations. However, immunoreactive plasma angiotensin II concentrations were not suppressed below pretreatment values, suggesting that chronic enalapril/acute enalaprilat therapy controls blood pressure through a nonangiotensin-mediated antihypertension mechanism.

Administration, Oral↗
PubMed1985

Effects of calcium entry blockers on renin-angiotensin-aldosterone system, renal function and hemodynamics, salt and water excretion and body fluid composition.

The renal effects of the calcium entry-blocking drugs diltiazem, nifedipine, verapamil and nitrendipine are reviewed. Although nifedipine stimulates plasma renin activity on a short-term basis, none of the calcium entry blockers produces a clinically significant 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 diltiazem and nifedipine increase salt and water excretion on a short-term basis, none of the calcium entry blockers produces a clinically significant sustained effect on salt and water excretion; serum electrolytes, urinary sodium and potassium excretion, body fluid composition and body weight are unchanged. Thus, 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↗
PubMed1985

Hemodynamic and renal function in essential hypertension during treatment with enalapril.

Enalapril (at a mean dose of 25 mg), a potent, long-acting angiotensin converting enzyme inhibitor, was prescribed in combination with hydrochlorothiazide (at a mean dose of 64 mg) for 96 weeks in 11 patients with essential hypertension who had pretreatment (placebo) glomerular filtration rates of less than 80 ml/minute/1.73 m2. Blood pressure was well controlled. After 56 weeks of therapy, glomerular filtration rate (assessed by inulin clearance) increased 55 percent and effective renal plasma flow (assessed by para-amino-hippurate clearance) increased by 32 percent; these increases were sustained through the 96 weeks of therapy. Furthermore, gains in renal function were sustained without adversely affecting 24-hour urinary protein excretion, sodium excretion, or body fluid composition. These results suggest that enalapril, in combination with hydrochlorothiazide, has the pharmacologic capability to favorably modify a primary pathophysiologic characteristic of essential hypertension by decreasing renal vascular and mesangial tone.

Adult↗
PubMed1985

Nutrition in renal transplantation.

This study was conducted to determine whether a high-nitrogen, low-carbohydrate diet in the immediate post-operative renal transplant period could result in a positive nitrogen balance and fewer cushingoid side effects. Twelve consecutive nondiabetic renal transplant recipients were randomly assigned to the isocaloric control or experimental diet group. The six patients ingesting the experimental diet achieved positive nitrogen balance whereas five of the six patients on the control diet had a negative nitrogen balance. The nitrogen balance varied directly and proportionately with the protein intake. Potassium balance mirrored the nitrogen balance data. Cushingoid side effects did not develop in any of the six experimental diet patients whereas four of the six control diet patients had evidence of severe cushingoid appearance and two had moderate cushingoid appearance (P = .01). Based upon the findings of this study, we suggest that the renal transplant recipient's diet could be altered to provide more protein and less carbohydrate to improve nitrogen balance and prevent cushingoid features. It is possible that a high-protein, low-carbohydrate diet may be used by additional patients taking steroids for other disease states to prevent cushingoid side effects and improve nitrogen balance.

Adult↗
PubMed1985

Effects of enalapril alone, and in combination with hydrochlorothiazide, on renin-angiotensin-aldosterone, renal function, salt and water excretion, and body fluid composition.

Enalapril is a new, oral, long-acting nonsulfhydral angiotensin converting enzyme inhibitor. Thirty-nine patients with primary hypertension were entered into a randomized, double-blind protocol to assess the efficacy of enalapril (10 to 20 mg bid), hydrochlorothiazide (25 to 50 mg bid), or combined drug therapy. Enalapril, either alone or in combination with hydrochlorothiazide, effectively controlled blood pressure. Enalapril monotherapy was associated with an increase in plasma renin activity and a decrease in angiotensin II concentration; in patients with an initial inulin clearance less than or equal to 80 mL/min/1.73 m2, inulin and para-aminohippurate clearances were markedly improved, without producing adverse effects on salt and water excretion or body fluid composition. Combination therapy was associated with a marked increase in plasma renin activity; however, only those patients with an initial inulin clearance less than or equal to 80 mL/min/1.73 m2 demonstrated suppression of angiotensin II concentration and marked improvement in inulin and para-aminohippurate clearances. These observations suggest that enalapril, either alone or in combination with a diuretic, has the potential to reverse renal function abnormalities encountered in the hypertensive state.

Body Fluids↗
PubMed1985

Pulmonary hemodynamics in systemic hypertension.

We reviewed cardiac catheterization data and the medical records of 30 patients with systemic hypertension to establish their pulmonary hemodynamic profiles and the relationship between certain clinical and demographic variables and increased pulmonary vascular resistance. Mean systemic arterial pressure ranged from 110 to 210 mm Hg, and systemic vascular resistance ranged from 17.6 to 47.0 units. Seven patients had normal pulmonary wedge pressure and normal pulmonary vascular resistance, one had elevated pulmonary wedge pressure and normal pulmonary vascular resistance, five had elevated pulmonary wedge pressure and increased pulmonary vascular resistance, and 17 had normal pulmonary wedge pressure and increased pulmonary vascular resistance. There were significant positive correlations between systemic vascular resistance and pulmonary vascular resistance and between mean systemic arterial pressure and mean pulmonary artery pressure, but there was no correlation between mean pulmonary wedge pressure and pulmonary vascular resistance. Of the 17 patients with normal pulmonary wedge pressure and increased pulmonary vascular resistance, seven had clinical or radiologic evidence of prior left ventricular failure. We conclude that increased pulmonary vascular resistance occurs commonly in patients with systemic hypertension. Although some cases of increased pulmonary vascular resistance relate to active or preexistent left ventricular failure, the majority remain unexplained, suggesting that neurohumoral or other factors may produce a hypertensive response in both the systemic and pulmonary arterial circuit.

Adult↗
PubMed1985

Enalapril versus triple-drug therapy in the treatment of renovascular hypertension.

18 renovascular hypertensive patients were entered into a randomised, double-blind protocol to assess the safety and efficacy of enalapril (5 to 20 mg twice-daily) and hydrochlorothiazide (50 to 100 mg/day), versus triple-drug therapy employing hydrochlorothiazide (50 to 100 mg/day), timolol (10 to 30 mg twice-daily) and hydralazine (50 to 150 mg twice-daily). Specifically monitored were the effects of each drug regimen on blood pressure, plasma renin activity and angiotensin II, glomerular filtration rate by insulin clearance, and effective renal plasma flow by para-aminohippurate clearance. Results indicate that enalapril/hydrochlorothiazide was more effective than triple-drug therapy in lowering blood pressure. All patients on enalapril/hydrochlorothiazide had excellent control of blood pressure, and there were no adverse effects. In contrast, 50% of the patients on triple-drug therapy had either uncontrolled blood pressure or significant drug-related side effects. Patients who were uncontrolled or intolerant of triple-drug therapy were well controlled on enalapril/hydrochlorothiazide. Patients on enalapril/hydrochlorothiazide demonstrated stimulation of plasma renin activity with inhibition of plasma angiotensin II, indicating adherence with therapy. Therapy for both unilateral and bilateral renovascular hypertension with enalapril/hydrochlorothiazide did not result in reductions in either glomerular filtration rate or effective renal plasma flow, except in 1 patient with a functional solitary stenotic kidney. In contrast, triple-drug therapy was generally associated with modest reductions in glomerular filtration rate and effective renal plasma flow, with a severe reduction in glomerular filtration rate and effective renal plasma flow occurring in 1 patient with bilateral symmetrical renovascular disease. We conclude that the combination of enalapril and hydrochlorothiazide is a safer and more effective regimen, compared with triple-drug therapy, for the treatment of renovascular hypertension.

Angiotensin II↗
PubMed1985

Adrenergic blocking agents and the kidney.

The acute and chronic renal effects of the beta-adrenergic antagonists, alpha 1-adrenergic antagonists, central alpha 2-adrenergic agonists, and central and/or peripheral adrenergic-neuronal blocking agents are reviewed. In general, beta-adrenergic antagonists have little or no clinical effect on glomerular filtration rate (GFR), effective renal plasma flow or renal blood flow (ERPF/RBF), renal vascular resistance (RVR), urinary sodium or potassium excretion, free water clearance, or body fluid composition. The alpha 1-adrenergic antagonists (prazosin and indoramin) have little or no clinical effect on GFR and ERPF/RBF; however, RVR is reduced. Sodium excretion is also reduced, leading to salt and water retention. The central alpha 2-adrenergic agonists (alpha-methyldopa, clonidine, and guanabenz) have little or no clinical effect on GFR and ERPF/RBF; however, RVR is reduced. Urinary sodium and potassium excretion and body fluid composition are unchanged. Free water clearance may be increased. The central and peripheral adrenergic-neuronal blocking agent reserpine has little or no clinical effect on GFR and ERPF/RBF; however, RVR is reduced. Urinary sodium, potassium, and water excretion and body fluid composition are unchanged. Finally, the peripheral adrenergic-neuronal blocking agents (guanadrel and guanethidine) decrease GFR and ERPF/RBF; RVR is also reduced. The filtered load and fractional excretion of sodium is decreased, producing expansion of body fluid spaces and weight gain.

Adrenergic alpha-Agonists↗
PubMed1984

Role of angiotensin converting enzyme inhibitors in essential and renal hypertension. Effects of captopril and enalapril on renin-angiotensin-aldosterone, renal function and hemodynamics, salt and water excretion, and body fluid composition.

Among the many generic classes of drugs currently being used for the treatment of hypertension, few, following long-term therapy, improve or correct the underlying renal function and hemodynamic abnormalities encountered in patients with sustained hypertension. This review focuses on the renal effects of the angiotensin converting enzyme inhibitors captopril and enalapril. Each drug is discussed in terms of its short- and long-term effects on the renin-angiotensin-aldosterone system, renal function and hemodynamics, salt and water excretion, and body fluid composition. Data are presented that demonstrate that enalapril, used alone or in combination with diuretic therapy, has the unique ability to control hypertension, to improve glomerular filtration rate and effective renal plasma/renal blood flow, and to decrease renal vascular resistance, without producing adverse effects on salt and water excretion or body fluid composition. If the safety of enalapril is confirmed in long-term studies, the drug will clearly assume a prominent role as either first- or second-step (in combination with a diuretic) therapy in the treatment of hypertension.

Body Fluids↗
PubMed1984

Comparative studies: enalapril versus hydrochlorothiazide as first-step therapy for the treatment of primary hypertension.

Thirty-nine patients were entered into a 12-week, randomized, double-blind, parallel protocol to assess the safety and efficacy of enalapril (MK-421, 10 to 20 mg bid), hydrochlorothiazide (HCTZ, 25 to 50 mg bid), or combined drug therapy (MK-421 + HCTZ) for the treatment of primary hypertension. Specifically monitored were the effects of each drug program on BP and pulse, serum chemistries, body fluid composition and weight, renal function, and the renin-angiotensin-aldosterone axis. Results indicate that MK-421, HCTZ, and combined therapy were equally effective in lowering BP; none of the therapies significantly altered glomerular filtration rate or effective renal plasma flow. Patients on MK-421 experienced no change in volume, an increase in plasma potassium, no change in fractional sodium or potassium excretion, and a decreased urine osmolality associated with an enhanced free-water clearance. Plasma renin activity was increased, plasma angiotensin II was decreased, and plasma aldosterone was unchanged. In contrast, patients on HCTZ developed volume contraction, hypokalemia associated with an increase in fractional sodium and potassium excretion, and an increased urine osmolality associated with a decreased free-water clearance. Plasma renin activity was increased, however, plasma angiotensin II and plasma aldosterone were unchanged. Patients on combined therapy with MK-421 + HCTZ demonstrated qualitatively similar changes in serum chemistries, body fluid volumes, and renal function compared with patients receiving HCTZ alone, whereas changes in the renin-angiotensin-aldosterone system in these patients were qualitatively similar, but more marked, compared with those occurring in patients receiving MK-421 alone. We conclude that MK-421 is an effective first-step antihypertensive agent that does not produce adverse metabolic, volume, or renal effects.

Antihypertensive Agents↗