Biomedical subjects

J H Bauer

Publications and source records attributed to J H Bauer.

At least 37 records · Page 2Linked to original sources

PubMed1991

The aging hypertensive kidney: pathophysiology and therapeutic options.

The aging kidney undergoes hemodynamic changes characterized by reductions in glomerular filtration rate and effective renal plasma flow. These functional changes are associated with loss of renal mass related to changes in the intrarenal vasculature. The reduced glomerular filtration surface area and subsequent microcirculatory adaptations enhance the risk for development of renal diseases associated with systemic diseases. Hypertensive nephrosclerosis accounts for 26% of all end-stage renal disease in the United States; the median age of those affected is 67 years. Hemodynamic and structural changes observed in the essential hypertensive kidney suggest an accentuation of the physiologic aging process. Initially observed hemodynamic changes, which may be reversible with specific drug therapy, suggest that excessive production of angiotensin II plays a role. Progressive renal impairment may occur despite control of systemic hypertension. Renal protection appears to require therapeutic normalization of both systemic and glomerular capillary pressures. The latter may depend on a drug's ability to attenuate the intrarenal effects of angiotensin II on the renal microcirculation. Drug classes with renal protective potential include angiotensin-converting enzyme inhibitors and calcium antagonists. However, long-term clinical trials are required to assess the potential advantages of specific drug therapies in preventing the development and/or progression of hypertensive arteriolar nephrosclerosis.

Aging↗

PubMed1991

Aneroid sphygmomanometers. An assessment of accuracy at a university hospital and clinics.

Defects of aneroid sphygmomanometers are a source of error in blood pressure measurement. We inspected 230 aneroid sphygmomanometers for physical defects and compared their accuracy against a standard mercury manometer at five different pressure points. An aneroid sphygmomanometer was defined as intolerant if it deviated from the mercury manometer by greater than +/- 3 mm Hg at two or more of the test points. The three most common physical defects were indicator needles not pointing to the "zero box," cracked face plates, and defective tubing. Eighty (34.8 of the 230 aneroid sphygmomanometers were determined to be intolerant with the greatest frequency of deviation seen at pressure levels of 150 mm Hg or greater. We recommend that aneroid manometers be inspected for physical defects and calibrated for accuracy against a standard mercury manometer at 6-month intervals to prevent inaccurate blood pressure measurements.

Blood Pressure Determination↗

PubMed1991

ACE inhibitors in renal disease.

Recent experimental studies suggest that the resistance state of the preglomerular and postglomerular capillary arterioles may determine if a particular class of antihypertensive agents will protect the kidney from hemodynamically mediated glomerular injury. This review discusses (1) the effects of angiotensin II on the renal microcirculation, (2) the pathophysiology of essential hypertensive renal disease, (3) the renal pharmacology of angiotensin-converting enzyme (ACE) inhibitors, and (4) the hypothesis that renal protection is dependent on control of systemic and glomerular hypertension.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1991

The effect of nifedipine GITS on renal function in hypertensive patients with renal insufficiency.

Twelve hypertensive patients with moderately severe renal dysfunction were entered into a protocol to assess the blood pressure and renal effects of the sustained release calcium antagonist, nifedipine GITS (30-180 mg/d given once a day) administered for 5 weeks. Nifedipine GITS monotherapy effectively lowered blood pressure in 50% of the patients. Glomerular filtration rate and effective renal plasma flow were increased 18% and 20%, respectively. The filtration fraction and urinary protein excretion remained unchanged. Changes that were observed in renal function were independent of the blood pressure responses of the patients; there was no correlation between the systemic and renal effect of nifedipine GITS monotherapy. Patients who had a poor systemic blood pressure response exhibited an increase in glomerular filtration rate (+11%) but had a decrease in effective renal plasma flow (-6%); patients who achieved a goal blood pressure response showed increases in both glomerular filtration rate (+35%) and effective renal plasma flow (+40%). These results show that nifedipine GITS monotherapy has the potential to improve renal function abnormalities that are encountered in hypertensive patients with renal disease; the improvement in renal function may be independent of their effect on systemic blood pressure.

Blood Pressure↗

PubMed1990

Acute and chronic effects of angiotensin converting enzyme inhibitors on the essential hypertensive kidney.

The natural course of essential hypertensive renal disease is characterized by a slowly progressive impairment of renal function. Initially, the changes are functional and reversible; however, structural changes gradually occur, leading to hypertensive nephrosclerosis. Similarities exist between the early functional hemodynamic changes observed in the essential hypertensive kidney and the physiologic renal effects of angiotensin II. To the degree that the initial functional changes are the result of excessive endogenous production of angiotensin II, interruption of the integrity of this humoral system could be expected to reverse the pathophysiologic sequence of events leading to hypertensive nephrosclerosis. This review focuses on the pathophysiology of the essential hypertensive kidney, the intrarenal effects of angiotensin II, and the acute and chronic effects of angiotensin converting enzyme (ACE) inhibition therapy on the essential hypertensive kidney. The data reviewed suggest that ACE inhibition therapy does reverse the initial functional hemodynamic changes observed in the essential hypertensive kidney and may protect the glomerulus from hemodynamically mediated injury.

Angiotensin II↗

PubMed1990

Effects of calcium antagonists on the hypertensive kidney.

This review focuses on the effects of calcium antagonists on renal function in hypertensive human subjects. Specifically assessed are the acute and chronic effects of diltiazem, verapamil, amlodipine, felodipine, isradipine, nicardipine, nifedipine, and nitrendipine on glomerular filtration rate; effective renal plasma flow/renal blood flow; renal vascular resistance; and urinary protein excretion. Among the calcium antagonists, only the dihydropyridine derivatives have been demonstrated consistently to acutely increase effective renal plasma flow/renal blood flow. The acute effects on glomerular filtration rate are variable. With respect to chronic therapy, many of the calcium antagonists have been reported to produce sustained increases in the effective renal plasma flow/renal blood flow and/or the glomerular filtration rate. Renal vascular resistance is reduced. Although calcium antagonists preserve or improve renal perfusion and glomerular filtration, long-term clinical trials are required to determine their potential therapeutic benefit to modify the natural course of hypertensive renal disease.

Calcium Channel Blockers↗

PubMed1990

Angiotensin converting enzyme inhibitors.

This review focuses on the use of angiotensin converting enzyme (ACE) inhibitors in hypertensive diseases. Specifically discussed are: proposed mechanisms of action, the pharmacology of the commercially available ACE inhibitors (captopril, enalapril, and lisinopril), their renal effects, and their safety and efficacy. The ACE inhibitors are assuming a dominant role in our therapeutic armamentarium, in that they are well-tolerated and very effective in the treatment of mild, moderate or severe hypertension.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1990

Intrarenal metabolism of angiotensin II.

This study investigated the intrarenal metabolism of circulating angiotensin II. Mean arterial pressure (MAP), renal hemodynamics, and the arterial, renal venous, and renal tissue concentrations of the angiotensin octapeptide [ANG-(1-8)] were examined following the constant intra-arterial infusion of tritiated angiotensin II [( 3H]ANG-(1-8)] in graded doses of 0.5, 2.0, and 2.5 ng.kg-1.min-1 in five uninephrectomized, anesthetized female dogs. The infusion of [3H]ANG-(1-8) had no significant effect on MAP, glomerular filtration rate, renal blood flow, or urine flow rate. The mean degradation rate of intra-arterially infused [3H]ANG-(1-8) was 72%. The net renal venous plasma concentration of ANG-(1-8) was greater than that predicted from the degradation rate of [3H]ANG-(1-8). High concentrations of ANG-(1-8) were measurable in all renal tissues. However, [3H]ANG-(1-8) was not detectable in any renal tissue. These observations suggest that ANG-(1-8) in the renal venous effluent was derived, in part, de novo from intrarenal generation. Likewise, renal tissue ANG-(1-8) was derived de novo from intrarenal generation.

Angiotensin II↗

PubMed1990

Renal protection in essential hypertension: how do angiotensin-converting enzyme inhibitors compare with calcium antagonists?

By interrupting the integrity of the systemic and renal renin-angiotensin system, angiotensin-converting enzyme inhibitors have been shown, experimentally, to preferentially reduce postglomerular capillary arteriolar resistance, to reduce glomerular capillary pressure, and to increase the ultrafiltration coefficient. Under normal physiological conditions, angiotensin-converting enzyme inhibitors have little effect on glomerular filtration rate; however, they increase effective renal plasma flow at renal perfusion pressures within the normal autoregulatory range and renal vascular resistance is decreased. In contrast, calcium antagonists have been shown, experimentally, to preferentially reduce preglomerular capillary arteriolar resistance. Their effects on angiotensin II and postglomerular capillary arteriolar resistance (hence, glomerular capillary pressure and the ultrafiltration coefficient) are controversial. Under normal physiological conditions, calcium antagonists increase both glomerular filtration rate and effective renal plasma flow at renal perfusion pressures within the normal autoregulatory range and renal vascular resistance is decreased. In patients with essential hypertension, studies have demonstrated that angiotensin-converting enzyme inhibitors (as predicted) sustain glomerular filtration rate, increase effective renal plasma flow, and decrease renal vascular resistance. However, essential hypertensive patients with impaired glomerular filtration rate may demonstrate marked improvement in both glomerular filtration rate and effective renal plasma flow. Calcium antagonists (as predicted) may increase both glomerular filtration rate and effective renal plasma flow (at high renal perfusion pressures) and may decrease renal vascular resistance. Calcium antagonists may also improve both glomerular filtration rate and effective renal plasma flow in patients with impaired glomerular filtration rate. Long-term clinical trials comparing the renal effects of angiotensin-converting enzyme inhibitors with those of calcium antagonists in essential hypertensive patients have not been reported. It remains to be determined if the potentially different effects of these two classes of antihypertensive drugs on the renal microcirculation do or do not translate into different renal protective advantages to patients at risk for the development and/or progression of hypertensive nephrosclerosis.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1990

Hypertension with co-existing renal disease.

It is generally accepted that treatment of systemic hypertension protects the kidney from haemodynamically-mediated injury. However, renal function may deteriorate during traditional antihypertensive therapy. Currently, hypertensive nephrosclerosis accounts for approximately 26% of all end-stage renal disease (ESRD) in the United States. Furthermore, in spite of aggressive treatment of hypertension, there is no evidence of a reduction in the incidence of hypertensive nephrosclerosis as a cause of ESRD. A current hypothesis states that renal protection is dependent on control of systemic hypertension (when present), and control of glomerular hypertension (when present). Since angiotensin II is a potent vasoconstrictor of the postglomerular capillary bed, which increases glomerular capillary pressure, it is attractive to hypothesize that drug therapies which can interrupt the intrarenal generation of angiotensin II (ACE inhibitors), or drug therapies which may attenuate the intrarenal actions of angiotensin II (calcium antagonists), may be renal protective. ACE inhibitors do control both systemic and glomerular hypertension. Calcium antagonists do control systemic hypertension; they may control glomerular hypertension. Long-term clinical trials in hypertensive patients, comparing the renal effects of ACE inhibitors with other antihypertensive drug classes (including calcium antagonists), have not been reported. It remains to be determined if the potential differing effects of antihypertensive drug classes on the renal microcirculation do, or do not, translate into differing renal protective advantages to patients at risk for the development and/or progression of renal disease.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1989

Effect of benazepril monotherapy in subjects with hypertension associated with renal dysfunction.

Nine hypertensive patients with mild to moderate renal dysfunction were entered into a protocol to assess the blood pressure, humoral and renal effects of the angiotensin converting enzyme inhibitor, Benazepril (CGS14824A, 2 to 20 mg twice daily) in patients with hypertension and moderate renal insufficiency (mean creatinine clearance 56 ml/min/1.73 m2). Specifically monitored, prior to and following 12 weeks of Benazepril monotherapy, were plasma renin activity and plasma aldosterone, the clearances of creatinine, Tc99m-diethylenetriaminepentaacetic acid (TC99m-DTPA) and para-amino-hippurate, and the 24-hour urinary excretion of protein. Blood pressure was well controlled. Plasma renin activity was stimulated, and plasma aldosterone was suppressed. Mean serum potassium increased from 3.9 to 4.2 mEq/L. Benazepril monotherapy had no adverse renal hemodynamic effect. Benazepril appears to be an effective antihypertensive agent in hypertensive patients with moderately impaired renal function.

Aged↗

PubMed1989

The effect of triple drug therapy on renal function in patients with essential hypertension.

The effects of long-term triple drug therapy on renal function in patients with moderate to severe essential hypertension have not been evaluated systematically. We prospectively studied fifteen male patients with moderate to severe essential hypertension receiving triple drug therapy (metolazone, atenolol or betaxolol, and minoxidil) for 16 weeks. Supplemental potassium was prescribed in an attempt to maintain serum potassium above 3.5 mEq/liter. Systemic blood pressure was well controlled with this regimen. However, glomerular filtration rate (assessed by inulin clearance), effective renal plasma flow (assessed by paraaminohippurate clearance), and renal blood flow were reduced. Filtration fraction and renal vascular resistance were not significantly altered. Plasma renin activity remained stimulated throughout the protocol. Weight gain occurred, and serum potassium remained low. These results suggest that triple drug therapy employing a diuretic, beta-adrenergic antagonist, and a potent vasodilator is effective therapy for controlling moderate to severe systemic hypertension. However this antihypertensive regimen may be associated with a decrement in renal function.

Adrenergic beta-Antagonists↗

PubMed1989

Short-term and long-term renal response to nifedipine monotherapy.

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 to 120 mg/d given in divided dosage) administered for twelve weeks. Nifedipine monotherapy effectively lowered blood pressure. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were increased following short-term therapy (four weeks); however, there was no net change in GFR or ERPF (compared to placebo) following long-term therapy (12 weeks). Renal vascular resistance was reduced. The filtration fraction and urinary albumin excretion was unchanged throughout the 12-week protocol. We conclude that nifedipine monotherapy does not adversely effect renal function. Tolerance occurs to the initial renal vasodilator response; hyperfiltration and hyperperfusion do not persist.

Clinical Trials as Topic↗

PubMed1989

Do calcium antagonists protect the human hypertensive kidney?

The natural course of essential hypertension, and hypertension associated with advanced renal parenchymal disease, is characterized by a progressive deterioration of renal function. If calcium antagonists can control both systemic and glomerular hypertension, they may be able to attenuate this process. Short-term studies in our laboratory suggest that the calcium antagonists amlodipine, diltiazem, and nifedipine preserve and/or improve renal function; there were no adverse effects on glomerular filtration, effective renal plasma flow, and/or urinary protein excretion. However, long-term clinical trials are required to determine if the observed short-term renal responses are sustained and if calcium antagonists protect the human kidney from systemic and glomerular hypertension.

Calcium Channel Blockers↗

PubMed1989

Renin inhibition with A-64662: effect on blood pressure and hormonal response in man.

We studied the effects of intravenous injections of the renin inhibitor A-64662 on blood pressure, plasma renin activity (PRA), angiotensin II (Ang II) and aldosterone levels in patients with essential hypertension. While PRA was completely suppressed with doses as small as 0.001 microgram/kg, blood pressure was affected only in a few instances in doses of 0.4-1.0 mg/kg. In the six patients in whom Ang II and aldosterone results were available these hormones were concomitantly reduced with PRA, although the PRA inhibition lasted much longer (up to 24 h). There was little relationship between the blood pressure changes and plasma levels of renin activity, Ang II and aldosterone, suggesting that the plasma pool of these variables may not be the crucial factor determining blood pressure responses in patients with essential hypertension.

Aldosterone↗

PubMed1989

Renal protection with calcium antagonism in essential hypertension.

The natural history of uncontrolled essential hypertension, with respect to renal function, is characterized by a progressive rise in renal vascular resistance, a progressive fall in effective renal plasma flow, and a progressive fall in glomerular filtration rate. Sustained effective antihypertensive therapy may reverse this pathophysiological sequence, preventing the development of arteriolar nephrosclerosis. It is unknown whether such a therapeutic benefit is a nonspecific response to controlling systemic hypertension, or is dependent on controlling both systemic and glomerular hypertension. Recent experimental evidence indicates that the control of systemic blood pressure may not necessarily be associated with control of glomerular capillary hypertension. The renal effects of calcium antagonists in essential hypertensive patients are only now being characterized. We have demonstrated that diltiazem, amlodipine, and nifedipine monotherapies enhance glomerular filtration rate and effective renal plasma flow, and lower renal vascular resistance. Although calcium antagonists attenuate the intrarenal effects of norepinephrine and angiotensin II, the precise mechanism(s) by which these drugs reverse the functional renal abnormalities in the essential hypertensive state, and by which they may attenuate the progression of hypertensive renal disease, are unknown. It is our hypothesis that renal protection requires normalization of both systemic and glomerular capillary pressure. Calcium antagonists have the ability to control systemic hypertension. If they can be demonstrated experimentally to reduce both pre- and post-glomerular capillary resistances (i.e. maintain a normal glomerular capillary pressure), they can be expected to provide long-term renal protection.

Calcium Channel Blockers↗

PubMed1989

Arterial-venous determinations of the "immunoreactive" angiotensin peptides in human subjects.

Simultaneous measurements of arterial and venous plasma "immunoreactive" angiotensin II and angiotensin II peptide fragments (octapeptide, heptapeptide, hexapeptide, and pentapeptide), done with high performance liquid chromatography and radioimmunoassay, were obtained in nine human subjects. Results indicate that the angiotensin II octapeptide is the major peptide fragment in both arterial and venous plasma. Approximately 80% of the "immunoreactive" angiotensin II measured in both arterial and venous plasma is the angiotensin II octapeptide fragment. The concentration of angiotensin II octapeptide in venous blood approximated the concentration of angiotensin II octapeptide measured in arterial blood. These data suggest that venous concentrations of angiotensin II octapeptide probably reflect the activity of the tissue renin angiotensin system, because its concentration was much higher than would be predicted from inactivation of arterial blood angiotensin II octapeptide in peripheral tissues.

Adult↗

PubMed1988

Effect of lisinopril monotherapy on renal hemodynamics.

Nineteen essential hypertensive patients were entered into a protocol to assess the BP, humoral and renal effects of the angiotensin converting enzyme inhibitor, lisinopril (MK 521, 20 to 80 mg once daily), administered for 52 weeks. Specifically monitored prior to, and following 12 and 52 weeks of lisinopril monotherapy were plasma renin activity and plasma aldosterone, the clearances of creatinine, inulin and para-aminohippurate, and the 24-hour urinary excretion of protein. BP was well controlled. Plasma renin activity was stimulated, and plasma aldosterone was suppressed throughout the entire protocol. In contrast to the reported short-term and long-term renal effects of enalapril, lisinopril (a lysine analog of enalapril) had no short-term effect on renal function: glomerular filtration rate, effective renal plasma flow, filtration fraction (FF), renal vascular resistance (RVR), and protein excretion were all unchanged. However, following long-term therapy, both FF and RVR were decreased. Lisinopril appears to convey no specific renal pharmacological benefit.

Aldosterone↗