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Biomedical subjects

M A Weber

Publications and source records attributed to M A Weber.

At least 127 records · Page 7Linked to original sources
PubMed1992

Fosinopril: a new generation of angiotensin-converting enzyme inhibitors.

Fosinopril, the first agent in a new chemical class of phosphorus-containing angiotensin-converting enzyme (ACE) inhibitors, has unique pharmacologic properties. Fosinopril administration leads to complete inhibition of plasma ACE activity for 12-24 h. In patients with normal renal function, approximately equal amounts of the drug are eliminated via the hepatic and renal routes. With worsening renal function, increasing amounts of fosinopril are eliminated hepatically. This dual elimination allows for the administration of fosinopril using the same starting dosage to any patient, regardless of renal function. Fosinopril may provide end-organ protection against the effects of hypertension and antihypertensive therapy; this drug potentially protects the kidney by increasing renal functional reserve, while maintaining cardiac left ventricular performance. Moreover, despite marked blood reductions, cerebral blood flow is maintained. Controlled trials show that fosinopril in single daily doses of 10-40 mg is efficacious and safe for the long-term treatment of hypertension. At these doses, favorable responses were seen in up to 80% of patients. Fosinopril is equally effective in elderly as well as younger patients and works in black as well as in nonblack patients. The incidence of adverse events does not differ significantly between fosinopril- and placebo-treated patients. Fosinopril represents a clinically useful agent for the treatment of hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Left ventricular hypertrophy and antihypertensive therapy.

Left ventricular hypertrophy is more common in hypertensive individuals than in normotensive persons. Its presence in hypertensive patients is associated with an increased incidence of ventricular arrhythmias, myocardial infarction, congestive heart failure, stroke and cardiovascular mortality. Echocardiography is more sensitive than electrocardiography in detecting left ventricular hypertrophy. Echocardiographic evidence of this condition in patients with borderline hypertension may identify those who need treatment. Weight reduction and drug therapy can prevent or reverse ventricular hypertrophy in hypertensive patients. Recent studies suggest that some antihypertensive drugs are more effective than others in reducing left ventricular hypertrophy. These agents include beta-adrenergic blockers, angiotensin converting enzyme inhibitors, calcium channel blockers and sympatholytic agents. Although little evidence exists to show that reduction of left ventricular mass decreases cardiovascular morbidity and mortality, avoidance of antihypertensive agents that may aggravate hypertrophy would seem prudent.

Antihypertensive Agents↗
PubMed1992

A dose escalation trial comparing the combination of diltiazem SR and hydrochlorothiazide with the monotherapies in patients with essential hypertension.

A multicentre, randomised, placebo-controlled parallel group study comparing various doses of the combination diltiazem SR (DTZ SR)/hydrochlorothiazide (HCTZ) with the monotherapies was performed to delineate the optimal antihypertensive dosage of the two drug combinations. The study was carried out in 298 patients with mild to moderate essential hypertension (stable supine diastolic blood pressure, DBP, greater than or equal to 95 and less than or equal to 110 mmHg). After a single-blind placebo lead-in period lasting 4-6 weeks to establish stable baseline BP, the patients were randomised to receive either placebo (n = 75), HCTZ (n = 76), DTZ SR (n = 72), or the combination of DTZ SR/HCTZ (n = 75). There were three 4-week evaluation periods with forced escalation of therapy as follows: HCTZ (6.25, 6.25, 12.5 mg twice daily), DTZ SR (60, 90, 120 mg twice daily), and the combination of DTZ SR/HCTZ (60/6.25, 90/6.25, 120/12.5 mg twice daily). DTZ SR/HCTZ (120/12.5 mg) produced statistically significantly greater reductions in supine DBP compared with each monotherapy and placebo. The lower doses of DTZ SR/HCTZ (60/6.25 mg and 90/6.25 mg) produced statistically significantly greater supine DBP reductions compared with DTZ SR monotherapy and placebo, but not compared with HCTZ monotherapy. A comparison of reduction in supine DBP between evaluation periods demonstrated a dose-response relationship for the combination therapy in reducing BP over the dosage range studied. Adverse clinical and laboratory events were not significantly different between the therapies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Norepinephrine amplifies angiotensin II-induced vasoconstriction in rabbit femoral artery.

Several reports have focused on the ability of angiotensin II to amplify vascular contractile responses to norepinephrine, but none have determined whether norepinephrine enhances angiotensin II-induced vasoconstriction. Measuring isometric contraction in isolated rabbit femoral artery rings, we have found that the angiotensin II-induced contractile response was amplified in the presence of a threshold contraction to norepinephrine, as manifested by a 2.9-fold leftward shift of the midpoint of the concentration-response curve with no change in the maximal response. This amplification was attenuated markedly by nifedipine (0.1 microM), a calcium channel antagonist, implicating calcium channel activation in the amplification phenomenon. Precontracting the smooth muscle with a threshold concentration of angiotensin II had no enhancing effect on further angiotensin responses, indicating that the norepinephrine-induced amplification was due to a specific action of norepinephrine, rather than to a precontraction itself. In experiments in which the angiotensin II response was diminished by the presence of the noncompetitive angiotensin II antagonist [Sar1 Ala8]angiotensin II (0.3 microM), norepinephrine affected the angiotensin II response primarily by increasing the maximal response attainable. Prazosin (0.1 microM) both blocked the norepinephrine threshold contraction and abolished completely the amplification. However, when the norepinephrine concentration was increased until a threshold contraction was elicited in the presence of a fixed concentration of prazosin, amplification of the angiotensin II response was restored. These results indicate that norepinephrine exerts its amplifying effect on angiotensin II via activation of alpha-1 adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1991

Cardiovascular and metabolic characteristics of hypertension.

Hypertension is now seen as a broader condition than high blood pressure alone. Large-scale epidemiologic studies have established that high blood pressure is associated with an increased risk of cardiovascular events, but clinical trials of antihypertensive therapy have shown an inconsistent reduction in major cardiovascular endpoints. Importantly, the incidence of coronary disease has been reduced to only a small extent, suggesting that factors beyond high blood pressure are important in the genesis of atherosclerotic disease in hypertensive patients. It is evident, for example, that patients with hypertension have an exaggerated vulnerability to the consequences of lipid abnormalities. Moreover, it has recently been established that hypertension is characterized by insulin resistance and altered glucose tolerance. As a result, high plasma concentrations of insulin produce proliferative effects on vascular smooth muscle and connective tissue, and they may adversely affect the lipid profile. The left ventricle is also involved in hypertension--independent of blood pressure. There is growing evidence that there are increases in the muscle mass of the left ventricle and changes in its diastolic filling characteristics at the very early stages of hypertension. The arterial circulation is similarly involved, for alterations in structure or function, reflected by diminished arterial compliance, can be demonstrated prior to the appearance of clinical hypertension. Treatment designed to protect hypertensive patients from cardiovascular events must not only be based on blood pressure, but must take into account all the components of the hypertension syndrome.

Blood Glucose↗
PubMed1991

Left ventricular diastolic filling alterations in normotensive young adults with a family history of systemic hypertension.

To characterize the cardiovascular consequences of a history of hypertension in first-degree relatives in normotensive young adults, 72 normotensive (diastolic blood pressure [BP] less than 90 mm Hg) healthy volunteers (age 18 to 30 years) were studied with 2 dimensionally guided M-mode echocardiography, pulsed Doppler echocardiography, and 2-hour automated BP monitoring. Of the 72 subjects, 19 (12 men and 7 women) had a family history of hypertension and were compared with 19 subjects without a family history of hypertension who were matched for systolic BP and gender. There were no detectable differences in 2-hour average BP, left ventricular (LV) mass or wall thickness, or echocardiographic systolic functional indexes between subjects with and without a family history of hypertension. Doppler-derived diastolic functional indexes demonstrated more prominent late diastolic filling in subjects with a family history of hypertension. Late diastolic transmitral flow time and flow velocity integral were greater (132 +/- 24 vs 117 +/- 17 ms, p less than 0.05; and 2.5 +/- 0.7 vs 1.9 +/- 0.5 cm, p less than 0.01, respectively). To measure possible gender-related effects of a family history of hypertension, the men and women were analyzed separately. The 12 men with a family history of hypertension had greater peak late (40 +/- 0.9 vs 31 +/- 0.8 cm/s, p less than 0.02) and ratio of late-to-early (0.64 +/- 0.19 vs 0.46 +/- 0.10, p less than 0.01) transmitral flow velocities and greater late transmitral flow velocity integrals (2.6 +/- 0.8 vs 1.9 +/- 0.5 cm, p less than 0.05) than the matched male control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Hypertension with concomitant conditions: the changing role of beta-adrenoceptor blockade.

Hypertension often is associated with concomitant conditions such as chronic obstructive lung disease, diabetes mellitus, ischemic heart disease, and peripheral vascular disease. Moreover, other cardiovascular risk factors, including dyslipidemias and abnormalities of glucose and insulin metabolism, are common in patients with hypertension. Conventional beta-blockers used for antihypertensive therapy can have adverse effects in patients with airway disease, diabetes, and peripheral vascular disease, and can exaggerate the other risk factors. Newer beta-blockers such as celiprolol, which have selective partial agonist activity expressed at beta 2-receptors, appear to avoid these problems. Celiprolol exhibits antianginal and antihypertensive efficacy without adversely effecting left ventricular systolic function or exercise performance. It also may cause regression of left ventricular hypertrophy. The stimulatory action of celiprolol on vascular beta 2-receptors enhances regional flow and may increase walking distance in patients with claudication. The reduction in renal vascular resistance demonstrated by this drug is associated with preservation of renal blood flow and function. Spirometric measurements of airway function are unchanged during celiprolol treatment. Similarly, there are no adverse effects on lipid or glucose concentrations. These new developments in beta-blocker pharmacology indicate that this class of agents could be used in patients with hypertension with concomitant diseases or risk factors other than high blood pressure.

Adrenergic beta-Antagonists↗
PubMed1991

Immediate blood pressure effects of the renin inhibitor enalkiren and the angiotensin-converting enzyme inhibitor enalaprilat.

The antihypertensive effects of the renin inhibitor enalkiren were compared with those of the angiotensin-converting enzyme inhibitor enalaprilat in 17 hypertensive patients (14 white, 3 black; mean age 57 years), whose renin systems had been stimulated by diuretic pretreatment. Patients were studied on 3 separate in-hospital days. On the first study day patients received placebo alone. On day 2 they received intravenous bolus doses of enalkiren (0.03 to 1.0 mg/kg), and on day 3, intravenous bolus doses of enalaprilat (0.625 to 1.25 mg). Each agent reduced systolic (p less than 0.01) and diastolic (p less than 0.01) blood pressure (BP) from baseline levels. The acute decrease in systolic BP of 18.5 +/- 0.4 mm Hg during enalkiren tended to be greater (p less than 0.01) than the decrease of 12.6 +/- 0.7 mm Hg during enalaprilat. Decreases in diastolic BP during enalkiren (11.9 +/- 0.4 mm Hg) were also slightly greater (p less than 0.1) than those during enalaprilat (9.2 +/- 0.4 mm Hg). Based on prestudy plasma renin activity (PRA), patients were divided into "high" renin (PRA greater than 3.5 ng angiotensin l/ml/hr; n = 6) and "low/normal" renin (less than 3.5 ng angiotensin l/ml/hr; n = 11) groups. Reductions in diastolic BP in the "high" renin group during enalkiren (30 +/- 5/20 +/- 3 mm Hg) tended to be greater (p less than 0.07) than those during enalaprilat (23 +/- 7/14 +/- 1 mm Hg); differences were not significant in the "low/normal" group (12 +/- 2/7 +/- 2 and 7 +/- 2/8 +/- 1 mm Hg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Antihypertensive dose-response relationships: studies with the selective alpha 1-blocking agent terazosin.

Terazosin is a selective alpha 1-adrenergic-blocking agent indicated for the treatment of hypertension. The aim of this multicenter study, performed in 256 patients with mild to moderate essential hypertension, was to define the dosing characteristics of terazosin (in the range of 1 to 80 mg) administered once daily. Patients were randomly assigned to placebo or active treatment groups; each group received 3 months of treatment, which comprised three ascending doses of terazosin, each administered for a 1-month period. As determined by conventional office measurements of supine diastolic blood pressure and by automated ambulatory blood pressure monitoring, there was a clear antihypertensive dose-response relationship for terazosin in the range of 1 to 5 mg daily. Except for the 80 mg dose, none of the doses above 5 mg (10 to 40 mg) appeared to provide additional efficacy. Both the office measurements and the monitoring data indicated that the ratio of trough (effect at the end of the dosing interval) to peak (maximum effect during the dosing interval) was at least 50% or greater during treatment with the 5 mg dose. Thus the 5 mg dose appeared to provide meaningful clinical antihypertensive efficacy and to sustain its effects throughout the full 24-hour period.

Adrenergic alpha-Antagonists↗
PubMed1991

Effects of angiotensin II on pressor responses to norepinephrine in humans.

In previous studies in the conscious rabbit and in isolated artery preparations, low doses of angiotensin II synergistically amplified the pressor effects of the sympathetic neurotransmitter, norepinephrine (NE). To determine whether these observations could be replicated in humans, 9 normal adult male volunteers (mean age: 34) each were given 3 i.v. doses of NE (25, 50 and 100 micrograms.kg-1.min-1) during consecutive 10 min infusion periods. On a second study day, the procedure was repeated during infusion of angiotensin II in a subpressor dose (1.25 ng.kg-1.min-1). The angiotensin II didn't alter the BP responses to NE, but it attenuated the heart rate (HR) decreases associated with the NE infusions by 80% (P less than 0.05), 42% (P less than 0.05) and 42% (P less than 0.1). The two study days were then repeated following 2 weeks of oral treatment with the angiotensin converting enzyme inhibitor captopril (which, despite significantly decreasing baseline BP, also tended to decrease HR). In the presence of captopril, the pressor responses to the NE challenges were reduced by 50% (P less than 0.05), 33% (P less than 0.05) and 13% (P less than 0.1) compared with the pre-captopril responses. Thus, angiotensin II in subpressor doses appears to enhance NE pressor effects by attenuating the compensatory HR responses, whereas inhibition of endogenous angiotensin II mechanisms weakens the BP-raising actions of NE. These findings in humans are consistent with earlier observations that the renin-angiotensin system can directly amplify sympathetic pressor effects in two separate ways: by modifying baroreceptor sensitivity and by enhancing the actions of norepinephrine on vascular smooth muscle.

Administration, Oral↗
PubMed1991

Arterial properties of early hypertension.

In addition to high blood pressure, hypertension is characterised by metabolic and cardiovascular abnormalities, including decreased arterial compliance. To evaluate arterial involvement in early hypertension, we have employed a technique that analyses the arterial pulse wave contour to separately quantify proximal compliance (aorta and large arteries) and distal compliance (small arteries and arterioles). Proximal compliance was 24% lower in patients with borderline (diastolic BP 90-99 mmHg, n = 22) and 33% lower in patients with established (n = 19) hypertension than in normals (n = 15); distal compliance was 58% and 61% lower. These differences were not age-dependent, for in 27 age-matched pairs, proximal and distal compliances were 22% (P less than 0.01) and 55% (P less than 0.01) lower in hypertensives (diastolic BP greater than or equal to 95 mmHg) than in normotensives. Moreover, independent of BP or age, both proximal (P less than 0.05) and distal (P less than 0.01) compliance values were significantly lower in subjects with a family history of hypertension than in those without. Proximal compliance correlated inversely with indices of BP variability and heart work measured by automated whole-day blood pressure monitoring. Thus, changes in the elastic properties of the distal arterial circulation, reflected by decreased compliance, occur at the initiation of hypertension and may be an early diagnostic marker. Low proximal compliance appears to be associated with established hypertension, and might be a determinant of cardiovascular prognosis.

Adult↗
PubMed1991

Applications of ambulatory blood pressure monitoring in clinical practice.

Traditionally, blood pressure has been measured by the sphygmomanometer in the medical office. There is growing evidence, however, that office blood pressures may not be typical of values throughout the day. Between 20% and 30% of patients diagnosed with hypertension in the office actually are normotensive at other times. Ambulatory blood pressure monitoring with small, portable devices that automatically measure blood pressure every few minutes throughout the day appears to be an appropriate tool when "white-coat" hypertension is suspected--i.e., for individuals whose hypertension in the physician's office is not associated with other physical or historical evidence for cardiovascular disease or with other risk factors. Used prudently, ambulatory monitoring is a cost-effective technique that potentially can prevent unnecessary treatment of patients. Moreover, whole-day measurements may correlate more closely than office measurements may correlate more closely than office measurements do with findings of cardiovascular disease. This new approach also has highlighted the circadian pattern of blood pressure, especially the sharp early to mid-morning increase that coincides with an increased tendency to major cardiovascular events. This has focused attention on directing antihypertensive therapy towards the morning hours. Ambulatory monitoring is now used routinely in studies of antihypertensive drugs. This technique has no placebo effect and takes fewer patients to assess drug efficacy than do conventional methods.

Antihypertensive Agents↗
PubMed1990

Low-dose aspirin versus anticoagulants for prevention of coronary graft occlusion.

The prevention of graft occlusion by aspirin (100 mg/day) or heparin followed by phenprocoumon was investigated in a randomized trial in 235 patients after aortocoronary bypass operation. Aspirin treatment started 24 hours before, and heparin 6 hours and phenprocoumon 2 days after surgery. The results of the vein graft angiography and the clinical outcome 3 months postoperatively did not differ: 22% of 218 vein graft distal anastomoses in the aspirin group and 20% of 272 in the anticoagulant group were occluded. At least 1 occluded distal anastomosis was present in 38% of 74 patients in the aspirin-treated group and in 39% of 86 in the anticoagulant group. Worst-case analysis of all randomized patients showed graft occlusions, cardiovascular complications or lost to follow-up in 42% of 122 aspirin-treated patients compared with 41% of 113 patients treated with anticoagulants. For grafts with endarterectomy the occlusion rate was lower in the aspirin (12% of 49) than in the anticoagulant (22% of 41) group (p less than or equal to 0.05). Increased perioperative blood loss in the aspirin group (1,211 +/- 814 ml in the first 48 hours vs 874 +/- 818 ml in the anticoagulant group [p less than or equal to 0.001]) without a higher reoperation rate indicates effective platelet inhibition with low-dose aspirin. Because occlusion rates were equal but high in these patients with advanced stage of coronary artery disease, a combination of low-dose aspirin and anticoagulation should be investigated to reduce graft occlusion rates further.

Aspirin↗
PubMed1990

Documentation of the effective length of action of antihypertensive treatment.

The technique of automated ambulatory blood pressure (BP) monitoring offers an innovative means for measuring BP throughout the 24-hour period. Recently available compact monitoring instruments have been shown to be accurate and to provide reproducible measurements of the circadian BP pattern. The monitoring procedure is advantageous in that it minimizes or avoids placebo effects during therapeutic trials. Moreover, its power makes it possible to draw statistically valid conclusions regarding efficacy in fewer patients than would be required if conventional methods were used. This procedure also enhances the diagnosis of hypertension by identifying patients with "office" or "white coat" hypertension, and thereby facilitates assessment of treatment effects in those patients who are truly hypertensive. Automated monitoring measures BP at critical times of the day, including the preawakening and early morning hours, and it enables peak and trough antihypertensive drug effects to be carefully quantified. Since patient compliance appears to be enhanced with once- or twice-daily dosing, antihypertensive agents with long durations of action (24 hours) are of considerable interest. This report reviews some recent studies in which the monitoring technique has been used to measure the efficacy and duration of action of differing antihypertensive drugs.

Acebutolol↗
PubMed1990

Antihypertensive monotherapy with tablet (prompt-release) diltiazem: multicenter controlled trials.

The tablet formulation of diltiazem has been available for the treatment of angina pectoris but has not been comprehensively evaluated in hypertension. This study's aim was to evaluate the efficacy, dose-response characteristics, and duration of action of tablet (prompt-release) diltiazem in mild to moderate hypertension. Three placebo-controlled trials were designed. The first (trial #1) evaluated the dose response of 120, 240, and 360 mg/day (q12h regimen) of diltiazem in parallel fixed-dose fashion using hourly blood pressures. The second (trial #2) evaluated a q12h titration from 240 to 360 mg/day, which could be switched to q8h. The third (trial #3) evaluated a q8h titration from 180 to 270 to 360 mg/day, followed by conversion to a q12h regimen. The goal was a supine diastolic blood pressure of less than 90 mmHg and 10 mmHg less than baseline. With doses of diltiazem increasing from 120 to 240 to 360 mg/day, there was a progressive decrease in the average mean arterial pressure, describing a dose response with 120 mg/day as the ineffective dose. The peak effect for each dose regimen was found at 6 hours, with significant reductions lasting over 10 hours in the 240 mg/day and 360 mg/day groups. Peak plasma concentrations occurred at 3 hours. The residual effect at the trough of the 240 mg/day and 360 mg/day doses was 48% and 53% of the peak effect, respectively. When titration was carried out on a q8h regimen, both systolic and diastolic blood pressures were significantly decreased. When the regimen was switched from q8h to q12h, the effect was not maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Assessment of left ventricular systolic and diastolic function with Doppler echocardiography in hypertensive patients receiving intravenous medroxalol.

Intravenous medroxalol, an alpha- and beta-adrenergic blocking agent, causes an immediate hypotensive effect. In 14 subjects with mild-to-moderate hypertension, cardiac output (CO) and cardiac index (CI) were significantly decreased without significant changes in stroke volume, reflecting the fact that a reduced CO and CI were related to decreases in heart rate. The vasodilator effect of intravenous medroxalol was not apparent with the dosages used in this study. Transient changes noted in two Doppler diastolic velocity indexes--mitral early diastolic peak flow velocity (PFVE) and the ratio of mitral late-to-early diastolic peak flow velocity (PFVA/E)--are suggestive of an improvement in left ventricular (LV) diastolic filling during medroxalol infusion, possibly related to changes in loading conditions. Systolic and diastolic blood pressure did not correlate with any of the Doppler diastolic and systolic indexes in our patient population. Reduced aortic peak flow velocity, rate of aortic flow acceleration, and the rate of mitral early diastolic deceleration were noted with increasing LV mass index, independent of age or blood pressure. Doppler echocardiography may be a useful tool in the assessment and follow-up of LV systolic and diastolic function in patients undergoing pharmacologic interventions.

Adrenergic alpha-Antagonists↗
PubMed1990

Antihypertensive effects of beta-blockers administered once daily: 24-hour measurements.

Whole-day automated ambulatory blood pressure (BP) monitoring was used to assess the duration of the antihypertensive actions of the beta-blockers atenolol (50 to 100 mg; n = 20) and acebutolol (400 to 800 mg; n = 19) each given once daily at 9 AM. When compared with its pretreatment 24-hour average, atenolol decreased diastolic BP by 10 +/- 2 mm Hg (p less than 0.01) and systolic BP by 12 +/- 2 mm Hg (p less than 0.01). Acebutolol decreased the 24-hour diastolic BP by 11 +/- 1 mm Hg (p less than 0.01) and systolic BP by 13 +/- 2 mm Hg (p less than 0.01). More specifically, a comparison of the two drugs during the final 6 hours (3 AM to 9 AM) of the dosing interval showed that the mean decrease in diastolic BP of 10.2 +/- 1.5 mm Hg with acebutolol was greater (p less than 0.05) than the decrease of 6.2 +/- 1.3 mm Hg with atenolol. Moreover, this final 6-hour effect of atenolol was less (p less than 0.01) than that observed during the first 18 hours of the day. The late effects of acebutolol did not change significantly from its early effects. The two agents also differed in their trough (final 2-hour decrease in diastolic BP) and peak (maximum 2-hour decrease in diastolic BP) effects: for atenolol the peak-to-trough difference was 7.8 +/- 3.1 mm Hg (p less than 0.05), whereas for acebutolol it was 3.8 +/- 4.2 mm Hg (N.S.). This study confirms the efficacy of atenolol and acebutolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Acebutolol↗