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Biomedical subjects

M A Weber

Publications and source records attributed to M A Weber.

At least 145 records · Page 8Linked to original sources
PubMed1990

Acute pharmacokinetic and hemodynamic effects of intravenous bolus dosing of nicardipine.

The antihypertensive effects, duration of action, and pharmacokinetics of intravenous bolus doses of nicardipine were investigated in a series of patients with mild-to-moderate hypertension. Patients with a supine diastolic blood pressure between 95 and 114 mm Hg and a heart rate less than 90 beats/min who received no other antihypertensive medications were included in the study. On separate study days, single intravenous bolus doses of 0.125, 0.25, 0.5, 1, 3, 5, and 7 mg of nicardipine were administered over a 2-minute period. Blood pressure and heart rate were measured for 6 hours after an intravenous bolus of nicardipine was given, and serum nicardipine levels were measured throughout the study. Although the antihypertensive effect occurred immediately during the bolus infusion, peak average decreases in systolic and diastolic pressure ranged from 20 to 25 and 15 to 44 mm Hg, respectively, and occurred 2.5 +/- 0.6 minutes after infusion. Heart rate increased by 12 to 40 beats/min during the peak effect. The mean duration of action after an intravenous bolus dose was 24 +/- 5 minutes. A dose-response relationship was observed, as both nicardipine dosage and plasma nicardipine concentration correlated with reduction in blood pressure. These data indicate that bolus administration of nicardipine may provide a practical approach for the rapid parenteral treatment of hypertensive states.

Blood Pressure↗
PubMed1990

Assessment of renin dependency of hypertension with a dipeptide renin inhibitor.

To evaluate the participation of the renin-angiotensin system in sustaining hypertension, we administered the specific dipeptide renin inhibitor enalkiren (A-64662) to 18 patients with essential hypertension. Ascending intravenous bolus doses (0.03, 0.1, 0.3, and 1.0 mg/kg) of the inhibitor were each given at 45-minute intervals to patients maintained on an ad libitum sodium diet who were studied while in bed in the semirecumbent posture. Enalkiren produced marked decreases in plasma renin activity (PRA) that were still evident 8 hours after completion of dosing. Systolic and diastolic blood pressures were decreased in a dose-dependent fashion without an effect on heart rate. Repetition of this procedure after patients were subjected to sodium depletion by 1 week of thiazide treatment produced amplified decreases in blood pressure. Despite the short plasma half-life of the inhibitor, these blood pressure-lowering effects were sustained for 4-8 hours when compared with parallel placebo administration in the same patients. Both the baseline PRA and the inhibitor-induced changes in PRA correlated significantly with blood pressure changes during the unstimulated and the sodium-depleted studies. However, effects of the inhibitor on diastolic blood pressure in the latter study correlated most closely with actual increases in renin produced by diuretic pretreatment. Thus, this specific renin inhibitor has demonstrated the dependency of blood pressure on the renin-angiotensin system even during basal conditions in hypertensive patients. Moreover, renin response to sodium depletion appears to be an attribute that additionally characterizes individual hypertensive patients.

Adult↗
PubMed1990

P-wave configuration as an indicator of echocardiographic indices of cardiac structure and function in normotensive adolescents.

We evaluated the associations of a bimodal P-wave in ECG lead V1 to cardiac structure and function in healthy normotensive adolescents. Two-dimensional-guided M-mode echocardiography, 12-lead ECG, and conventional and 2-hour averaged automated blood pressure (BP) measurements were obtained in 40 normotensive (conventional BP less than 140/90 mm Hg) adolescents (mean age, 13 +/- 1 years). Compared with subjects with simple unimodal P-waves (n = 18), those with a normal yet bimodal P-wave in lead V1 (n = 22) had higher two-hour averaged systolic BP (108 +/- 12 mm Hg vs 99 +/- 7 mm Hg, p less than 0.01) and conventional sphygmomanometer systolic BP (110 +/- 11 mm Hg vs 103 +/- 10 mm Hg, p = 0.05). Structurally, the bimodal P-wave group had greater left ventricular mass (174 +/- 40 g vs 144 +/- 26 g, p less than 0.01), and functionally, they had a greater stroke volume (68 +/- 15 ml vs 57 +/- 13 ml, p less than 0.05) than the unimodal P-wave group. In the group with bimodal P-waves, left atrial size was directly related to left ventricular mass (r = 0.63). By step-wise multiple linear regression analysis, this correlation coefficient increased to 0.74 with inclusion of heart rate and to 0.82 with inclusion of systolic BP. Although left atrial size was similar in the unimodal and bimodal P-wave groups, it was unrelated to any parameter in the unimodal P-wave group. Thus, a bimodal P-wave in lead V1, while generally considered a normal variant, is associated with slightly higher systolic BP, significantly greater left ventricular mass, and greater stroke volume. Additionally, a bimodal P-wave in V1 is predictive of the parameters that influence left atrial size, especially left ventricular mass. While all of these findings fall within the traditionally defined normal ranges, the existence of a bimodal P-wave might identify young individuals who are vulnerable to early cardiovascular manifestations of hypertension.

Adolescent↗
PubMed1989

Hypertension in the aged: a pathophysiologic basis for treatment.

According to major surveys, hypertension is found in over half the population aged 65 years or over. In this age group, systolic blood pressure is at least as important as diastolic blood pressure as a predictor of cardiovascular morbidity and mortality. Overall, the presence of hypertension is associated with approximately a threefold increase in the likelihood of major events. Differing factors contribute to the hypertension. Loss of proximal arterial compliance, affecting the larger conduit vessels, occurs often with aging and explains the tendency for systolic pressure to increase while diastolic pressure remains constant or even decreases. A loss of baroreceptor sensitivity also may contribute to hypertension. There is an increase in responsiveness of the sympathetic nervous system and an enhanced sensitivity to its effects in the elderly, perhaps reflecting a decline in the buffering activity of peripheral vascular beta receptors. It is possible, too, that sodium retention may contribute to hypertension in some older patients. Although diuretics traditionally have been the mainstay of treatment in these patients, it is now recognized that other classes of antihypertensive agents may be equally as effective yet less prone to metabolic or symptomatic adverse events. Sympatholytic drugs, calcium channel blockers and angiotensin-converting enzyme inhibitors, either as monotherapy or in combination with low-dose diuretics, have been shown to be efficacious in the elderly. These agents also can produce regression of left ventricular hypertrophy, an additional property that may contribute to a reduction in serious cardiac complications.

Age Factors↗
PubMed1989

Mild hypertension in the elderly. A comparison of prazosin and enalapril.

In a single-blind, crossover study, prazosin and enalapril monotherapies were evaluated in 15 patients, aged 55 years or older (average age, 64 years), with mild hypertension (sitting diastolic blood pressure between 90 and 104 mm Hg). After eight weeks of placebo administration, patients were randomly assigned to treatment with prazosin or enalapril and then treated with the alternate drug after a second eight-week placebo washout period. The dose was titrated from 1 mg to a maximum of 10 mg twice daily of prazosin and from 2.5 mg to a maximum of 20 mg twice daily of enalapril to achieve a reduction in diastolic blood pressure to less than 85 mm Hg, with a decrease of at least 10 mm Hg based on clinical measurements of blood pressure. Patients received maintenance therapy with each medication for at least eight weeks. The response to therapy was then evaluated with two-hour periods of automated blood pressure monitoring. Average systolic and diastolic blood pressures for all patients during these two-hour monitoring periods decreased by 10.3 +/- 1.9/8.3 +/- 1.5 mm Hg during prazosin therapy and by 9.0 +/- 5.1/5.8 +/- 3.4 mm Hg during enalapril therapy. All patients responded to one of the two drugs, but only 50 percent responded to both. Side effects were generally mild and transient, and no significant metabolic effects were observed. Both prazosin and enalapril were effective and well tolerated in this population of elderly patients with mild hypertension.

Aged↗
PubMed1989

Clinical pharmacology of centrally acting antihypertensive agents.

The centrally acting agents are one of several differing classes of drugs now available for antihypertensive therapy. The availability of newer pharmacologic classes, including the beta-blockers, alpha-blockers. ACE inhibitors and calcium channel blockers, has resulted in a relative decline in the use of the centrally acting drugs. A major reason for this change in emphasis has been the perception by clinicians that the centrally acting agents, although effective, tend to produce symptomatic side effects that are difficult or unacceptable for patients. Some recent innovations in administering the centrally acting drugs appear to have addressed this problem. The pharmacokinetic characteristics of agents such as the transdermally administered clonidine or oral guanfacine appear to provide them with sustained efficacy without concomitant adverse effects. A further attribute of these drugs is their ability to decrease blood pressure without producing sodium retention. A growing awareness of the importance of treatment-induced metabolic effects has further served to reawaken interest in these agents. Specifically, they do not appear to produce alterations in glucose metabolism, and possibly may even have some slight beneficial effects on the blood lipid profile. Their ability to cause regression of left ventricular muscle hypertrophy, and possibly to enhance diastolic function, may add a further dimension of cardiovascular protection beyond their antihypertensive efficacy.

Antihypertensive Agents↗
PubMed1989

Central nervous system mediated vasodepressor action of atrial natriuretic factor.

Administration of 20, 4 or 2.5 micrograms/kg of atriopeptin III (AT III) into the fourth ventricle of the brain of spontaneously hypertensive rats produced a 13, 14 and 7 mm Hg decrease in MAP respectively, while 1 microgram/kg had no effect on MAP and was significantly different from 20 or 4 micrograms/kg (p less than 0.025). In contrast, injection of AT III 20 micrograms/kg into the lateral ventricle did not produce a change in MAP. To examine an interaction of AT III with the opioidergic system, the opiate antagonist, naloxone HCl, 10 micrograms, was given by ICV injection 10 minutes prior to AT III, and significantly prevented the depressor response to AT III (p less than 0.025 compared with AT III alone). Injection of specific anti-sera to beta-endorphin failed to prevent the AT III-induced depressor response. Our results demonstrate that AT III can act within the central nervous system to decrease the MAP of rats, most likely at a locus in proximity to the fourth ventricle of the brain. Further, an interaction with the central opioidergic nervous system underlies the central effects of AT III.

Animals↗
PubMed1989

Effects of a human-derived sodium transport inhibitor on in vitro vascular reactivity.

Concentrations of sodium-transport inhibitors (STI) which block the sodium-potassium-ATPase pump are increased in the plasma and urine of volume-expanded and low-renin hypertensive humans and animals. To evaluate the physiologic relevance of STI to blood-pressure-raising mechanisms, we have examined the in vitro properties of STI extracted from the urine of human subjects. STI produced a significant (by ANOVA: P less than .01) dose-contraction response in the isolated rabbit femoral artery. Moreover, small noncontractile doses of STI in this in vitro preparation produced a fivefold leftward shift in the contraction dose-response curve of norepinephrine (P less than .01) and a threefold shift for angiotensin II (P less than .01); at lower, physiologic, concentrations of these vasoconstrictor hormones the amplifications in contraction caused by STI ranged from 100% to 500%. In studies in calcium-free tissue bath solutions, the direct contractile action of STI was abolished; however, its amplification of responses to norepinephrine remained, suggesting that this latter effect of STI is not entirely dependent upon calcium influx into vascular smooth muscle cells. The glycoside ouabain produced effects identical to those of STI in arteries, but its actions on a rabbit atrium preparation were different: ouabain stimulated powerful inotropic effects, whereas human STI failed to cause myocardial contractions even though the amounts of STI administered had the same sodium-transport inhibitory capacity as the ouabain. Thus, the actions of human STI are primarily in the peripheral circulation, where they directly produce arterial contractions and also enhance contractile responses to other pressor hormones, suggesting that they may have a role in regulating systemic blood pressure.

Angiotensin II↗
PubMed1989

Sympathetic nervous system and hypertension. Therapeutic perspectives.

The sympathetic nervous system has a key role in the physiological regulation of the circulation and may also mediate some of the factors that cause or sustain clinical hypertension. Most classes of antihypertensive drugs produce at least part of their effects by inhibitory actions on the sympathetic pathways. The centrally acting agents and the peripheral alpha-adrenergic blockers are the most specific currently used sympathetic inhibitors. The available alpha-blockers, prazosin and terazosin, effectively reduce blood pressure when used as monotherapy or in combination with other antihypertensive drugs. When given once daily, the actions of terazosin persist throughout the full 24-hour period, including the important midmorning hours when there may be heightened sympathetic activity. The incidence of symptomatic adverse effects with the alpha-blockers is low. Because they specifically block peripheral alpha-receptor-mediated vasoconstriction, the alpha-blockers decrease total peripheral resistance at rest and do not antagonize the appropriate vasodilatory responses to exercise. They maintain or increase blood flow in regional circulations; cerebral blood flow in elderly patients is unchanged despite significant decreases in systemic blood pressure. In contrast to other drug classes that can adversely affect the lipid profile, the alpha-blockers slightly decrease total cholesterol concentrations. Recent studies also have shown that terazosin and prazosin can promote decreases in echocardiographically measured left ventricular wall thickness and muscle mass in hypertensive patients with left ventricular hypertrophy. Thus, this type of sympathetic blockade not only produces antihypertensive effects, but additionally may have a beneficial impact upon other cardiovascular risk factors.

Adrenergic alpha-Antagonists↗
PubMed1989

Comparison of antihypertensive therapies by noninvasive techniques.

We compared the antihypertensive effects of the beta-blocker atenolol and the converting enzyme inhibitor lisinopril during 12 weeks of treatment in patients with mild to moderate essential hypertension. Atenolol (n = 10) significantly decreased conventionally measured blood pressure from 144/103 to 135/93 mm Hg and lisinopril (n = 9) from 150/104 to 130/92 mm Hg. Based on data derived from automated 24-h ambulatory blood pressure monitoring, atenolol decreased the average whole-day systolic pressure by 18 +/- 6 mm Hg (p less than 0.02) and the diastolic pressure by 11 +/- 2 mm Hg (p less than 0.01). Lisinopril produced decreases of 27 +/- 5 mm Hg (p less than 0.01) and 13 +/- 2 mm Hg (p less than 0.001). Examination of the 24-h blood pressure patterns showed that the efficacies of the two drugs were similar. Each appeared to be effective throughout the whole-day monitoring period, although only lisinopril significantly decreased blood pressure during the final four-h period (4 AM to 8 AM) preceding the next day's dose. Neither drug produced significant echocardiographic changes in left ventricular wall thickness or muscle mass during the short-term treatment. Lisinopril and atenolol effectively decrease blood pressure during a 24-h period. Moreover, we found that automated whole-day blood pressure monitoring is a useful tool for comparing the efficacy and duration of action of differing antihypertensive agents.

Adult↗
PubMed1989

Assessing duration of antihypertensive effects with whole-day blood pressure monitoring.

The whole-day blood pressure response to once-daily and twice-daily administration of a combination of captopril and hydrochlorothiazide was measured in a study of elderly patients (aged 59 to 78 years) with mild to moderate hypertension. Whole-day automated ambulatory blood pressure profiles were obtained at baseline, after 8 weeks of therapy with a combination of 25 mg of captopril and 15 mg of hydrochlorothiazide twice daily, and again after 8 weeks of once-daily therapy with 50 mg of captopril and 25 mg of hydrochlorothiazide. Average systolic and diastolic whole-day blood pressures significantly decreased from baseline during both twice-daily treatment (mean +/- SEM change, 18 [+/- 3]/10 [+/- 2] mm Hg) and once-daily treatment (11 [+/- 2]/9 [+/- 1] mm Hg). While the decrease in systolic blood pressure during once-daily therapy was less than that during twice-daily therapy for the group as a whole, 16 of 19 patients achieved normal systolic (less than 140 mm Hg) and diastolic (less than 90 mm Hg) blood pressures throughout the day during the once-daily regimen. During once-daily therapy, the blood pressure reductions were sustained throughout the 24-hour period, and were not attenuated during the final 2 to 4 hours before the next dose. A subgroup of 5 patients were identified who appeared unresponsive to both twice-daily and once-daily antihypertensive treatment. Despite hypertensive office-measured blood pressures at entry to the study, 4 of these 5 patients actually had normotensive whole-day blood pressure averages at baseline (mean, 131 [+/- 7]/81 [+/- 4] mm Hg). Thus, whole-day ambulatory blood pressure monitoring is a valuable tool for testing treatment responses. It demonstrated that once-daily treatment with low doses of captopril and hydrochlorothiazide was as effective as twice-daily administration in decreasing diastolic pressures throughout the day, but was slightly less effective in decreasing systolic pressures. Additionally, the monitoring identified apparently normotensive patients in whom treatment may not be indicated.

Aged↗
PubMed1989

Antihypertensive treatment. Considerations beyond blood pressure control.

Treatment of patients with mild to moderate essential hypertension is now commonly undertaken. Clinical trials have shown a marked decrease in strokes in treated hypertensive patients. But despite reports of decreases in coronary deaths in some trials, the overall incidence of coronary events has been largely unaffected. This disappointing outcome has raised interesting issues. The patients in comparative placebo groups often do better than expected in formal trials; apart from the benefits of lifestyle changes, many of these patients appear to normalize their blood pressures during the trial. This latter effect can be due to erroneous diagnoses of hypertension at the start of the study, and this partially dilutes the likelihood of differences in outcome between the placebo- and actively treated patients. Optimal control of blood pressure is difficult to define, and controversies exist concerning whether pressures have been decreased insufficiently or excessively in clinical trials; it has been argued, too, that systolic as well as diastolic hypertension should be the target of treatment. Inadvertent treatment-induced metabolic abnormalities, especially in blood lipids, glucose, and electrolytes can weaken the antihypertensive benefits. Failure to deal with concurrent risk factors including smoking and left ventricular hypertrophy also could explain the absence of a decrease in coronary events. Newer classes of antihypertensive agents offer the potential to address these concerns and improve the cardiovascular prognosis of treated hypertensive patients.

Antihypertensive Agents↗
PubMed1988

Automated blood pressure monitoring for the assessment of antihypertensive treatment.

Whole-day automated monitoring with small portable devices allows the circadian pattern of blood pressure to be assessed conveniently in individual patients. Measurements provided by this technique appear to be more reproducible and physiologically relevant than conventional office readings. Ambulatory monitoring can enhance the evaluation of antihypertensive therapy, especially in clinical trials, in 3 ways. First, it can facilitate the diagnosis of hypertension and avoid potentially inappropriate treatment in patients whose hypertension is erroneously diagnosed by office measurements. Moreover, the monitoring technique appears to prevent placebo responses in therapeutic studies. Second, whole-day monitoring allows clear quantification of treatment effects. Because the standard deviations of treatment-induced blood pressure differences are lower with this method than with conventional readings, valid statistical evaluation of antihypertensive effects can be performed with far fewer patients. Finally, duration of action of drugs can be measured. By dividing the day into sequential periods (typically 12 two-hour periods), it is possible to determine statistical differences between baseline and treatment blood pressure values throughout the dosing intervals of the drugs being tested. This method may be more sensitive than the traditional "peak and trough" approach for assessing duration of action; it is not influenced by unsuspected discrepancies between the pharmacokinetic and pharmacodynamic properties of drugs, and can also provide information on nighttime effects. Thus, automated whole-day blood pressure monitoring appears to be a powerful tool for the evaluation of antihypertensive therapy.

Blood Pressure Determination↗
PubMed1988

Characterization of antihypertensive therapy by whole-day blood pressure monitoring.

Whole-day ambulatory monitoring is used for diagnosing hypertension and for judging response to treatment. We evaluated both of these properties in an antihypertensive trial with the calcium channel blocker diltiazem hydrochloride. Measured by a conventional sphygmomanometer, systolic and diastolic blood pressures fell significantly in patients who received diltiazem, whereas no consistent changes occurred in those who received placebo. Administration of the drug also decreased systolic and diastolic blood pressures evenly throughout the day, as determined by automated monitoring. The 15 diltiazem-treated patients were subdivided into those whose clinically diagnosed hypertension was confirmed by pretreatment blood pressure monitoring (24-hour average diastolic blood pressure, greater than or equal to 90 mm Hg; n = 9) and those whose 24-hour blood pressures failed to meet this criterion (n = 6). Diltiazem therapy decreased average whole-day blood pressures by 18/13 mm Hg in the hypertensives but by only 0/1 mm Hg in the others. Thus, whole-day blood pressure monitoring strengthens antihypertensive trials by documenting efficacy and duration of treatment. In addition, it enhances the diagnosis of hypertension, thereby identifying those patients in whom treatment seems justified.

Adult↗
PubMed1988

Safety issues during antihypertensive treatment with angiotensin converting enzyme inhibitors.

When captopril was first introduced, it was used in high doses for severe hypertension, often in the presence of renal insufficiency, and side effects such as proteinuria, rash, neutropenia, and altered taste sensation were noted. Upon analysis, these effects were most commonly seen in patients with renal disease, autoimmune disease, or collagen vascular disease. These complications usually reversed rapidly upon discontinuation of treatment. In contrast, the growing use of the angiotensin converting enzyme inhibitors, captopril and enalapril, for treating mild to moderate hypertension and the trend toward the use of lower doses has shown these agents to be well tolerated with a low frequency of troublesome adverse effects. In fact, the original spectrum of adverse effects has virtually disappeared with the use of lower doses in patients with uncomplicated hypertension. In low doses, the converting enzyme inhibitors produce remarkably few incidences of symptomatic discomfort; the most common is skin rash, which often responds to dosage reduction. Cough and rare occurrences of angioedema have also been reported. Moreover, evidence is evolving that indicates that the converting enzyme inhibitors may sometimes decrease proteinuria and improve renal function; these effects may be especially important in diabetic hypertensive patients. Of note, these drugs can also attenuate the unwanted metabolic side effects of concurrent diuretic treatment.

Angioedema↗